INTRODUCTION — Breast cancer is the most common female cancer in the United States, the second most common cause of cancer death in women (after lung cancer), and the primary cause of death in women ages 45 to 55. Early detection and treatment can often lead to a cure. Cure is most likely in women whose breast cancers are confined to the breast, while a substantial number of women whose tumors have spread to the local lymph nodes in the armpit (also called the axilla) can also be cured with appropriate therapy.
Occasionally, a breast cancer will not be discovered until it is fairly large or locally advanced. The term locally advanced breast cancer (LABC) is used to describe a breast cancer that has progressed locally but has not yet spread beyond the breast and regional lymph nodes. LABC includes large breast tumors (more than 5 centimeters in diameter), those that involve the skin of the breast or the underlying muscles of the chest wall, and cancers that have extensive involvement of the regional lymph nodes (those located in the axilla or in the soft tissues above and below the collarbone). It also includes inflammatory breast cancer, a rapidly growing type of cancer that makes the breast appear red and swollen (hence the term inflammatory).
Although the likelihood of curing LABC is lower than it would be if the cancer were small and confined to the breast, cure is possible with aggressive treatment. In most cases, this requires a combination of chemotherapy, radiation therapy, and surgery.
This topic review will cover the treatment of locally advanced breast cancer, including inflammatory breast cancer. Breast cancer is a very complex topic. An introduction to breast cancer and an overview of available treatments is available elsewhere. (See "Patient information: Breast cancer guide to diagnosis and treatment").
SIGNS AND SYMPTOMS
Locally advanced breast cancer (LABC) — Most LABCs can be felt (palpated) by both the patient and her doctor; they may also be visible. A careful physical examination of the breasts, skin of the chest, and regional lymph nodes (in the axilla and above the collarbone) is the first step in evaluation.
LABC is suspected if the tumor measures more than 5 cm across, or if it is fixed or attached to the underlying muscles or overlying skin of the chest wall. The finding of skin nodules on the affected breast, lymph nodes above or below the collarbone (called supraclavicular and infraclavicular nodes), or axillary lymph nodes that are non-movable and either attached to the underlying tissues (fixed) or to each other (matted) also suggests LABC.
Inflammatory breast cancer — Inflammatory breast cancer (IBC) is a specific type of LABC which produces a unique set of symptoms. IBC often does not produce a distinct mass or lump that can be felt within the breast. Instead, it causes thickening and swelling of the skin of the breast, which may be reddened and warm to the touch (show picture 1 and show picture 2). The breast is often painful and enlarged, and appears inflamed.
IBC may initially be confused with other inflammatory breast conditions, particularly infections. For example, women who are breastfeeding may develop a breast abscess or mastitis, which can produce symptoms similar to IBC. However, these conditions are usually associated with a fever and other evidence of infection (such as an increase in the number of white blood cells) that distinguish them from IBC.
DIAGNOSIS AND STAGING — Once the diagnosis of a breast cancer is suspected, several procedures must be done to confirm the diagnosis and establish the extent of tumor involvement, both within the breast and elsewhere in the body.
Mammogram — A mammogram of both breasts is needed to visualize the extent of tumor involvement within the breast and to make certain that the opposite breast is unaffected. Other tests such as a breast magnetic resonance imaging (MRI) study or ultrasound may be recommended (show radiograph 1).
Biopsy of the tumor — In order to confirm the diagnosis and type of breast cancer, a biopsy is required. A needle biopsy of the tumor, performed in the office, is usually sufficient to obtain enough tissue for the pathologist to study under the microscope.
The pathologist will also perform other tests to determine if the tumor is making hormone receptors and a protein called Her2 (also called erbB-2). These two factors are important in selecting the best treatment.
Hormone receptors — About 50 to 70 percent of breast cancers require the female hormone estrogen (estradiol) to grow; other breast cancers are able to grow without estrogen. Estrogen-dependent breast cancer cells produce molecules called hormone receptors, which are essential for the cell to use estrogen for growth. These hormone receptors can be estrogen receptors (ER), progesterone receptors (PR), or both.
If hormone receptors are present within a breast cancer, women are significantly more likely to benefit from treatments that lower estrogen levels or block the actions of estrogen, thus depriving the cancer cells of the material that stimulates their growth. These treatments are referred to as endocrine or hormone therapies, and such tumors are referred to as "hormone-responsive". In contrast, women whose tumors do not contain any ER or PR do not benefit from adjuvant hormone therapy.
HER2 expression — HER2 is a protein that is present on about one-third of breast tumors. The finding of HER2 within an individual breast cancer is an important indicator of benefit from a drug called trastuzumab (See "Trastuzumab (Herceptin®)" below).
Staging workup — Once the diagnosis of breast cancer is established, additional studies are performed to stage the cancer (determine how far it has spread). The stage of a breast cancer is based upon tumor size, involvement of the skin, chest wall or regional lymph nodes, and whether the cancer has spread to the bones or other organs (called metastasis).
The following studies may be recommended to search for evidence of spread to other organs: Blood tests, including a complete blood count and liver function tests Bone scan Chest X-ray or CT scan CT scan of the abdomen and pelvis CT scan or magnetic resonance imaging (MRI) of the brain A PET scan
After a complete evaluation, the size and extent of the breast tumor, type and extent of lymph node involvement, and the presence or absence of spread to other organs are grouped together to form the stage grouping of a breast cancer, which ranges from stage I to IV. A description of each stage is provided in table 1 (show table 1) Locally advanced breast cancer is stage III disease, and the presence of IBC makes the cancer a stage IIIB cancer
In contrast, women who have stage I or II breast cancer are referred to as having early stage disease, while stage IV means that spread to other organs has taken place.
Staging the axilla — The majority of patients with LABC have lymph nodes or glands that can be felt or palpated in the axilla by their physician. For the minority who do not have palpable axillary nodes, formal assessment of these nodes is often considered before beginning therapy. Knowing if the lymph nodes in the axilla are involved with the cancer can influence the choice of therapy. Surgery to remove some or all of these lymph nodes is the only accurate way to determine if the cancer has spread to the axillary lymph nodes.
Complete removal of the axillary lymph nodes (called axillary lymph node dissection or ALND), has traditionally been a routine component of the management of breast cancer. However, one of the most feared complications of ALND is swelling of the arm (called arm edema), the severity of which depends on the extent of the ALND and the use radiation therapy of the axilla. Thee need to accurately identify women who have involved lymph nodes while minimizing the chance of arm swelling led to the development of the sentinel node biopsy technique. (See "Patient information: Lymphedema after breast cancer surgery").
Sentinel node biopsy — The sentinel lymph node (SLN) concept is based on the premise that tumor cells that have broken off from a breast tumor first involve one or a few lymph nodes before involving other nodes or spreading elsewhere. To identify this node, the surgeon injects dye, a radioactive material, or a combination of both into the area surrounding the tumor, where it enters lymphatic channels and then flows to lymph nodes. If an SLN is identified, it is removed and examined under the microscope. If this node is negative, the chance of the other axillary nodes being also negative is good, and such women may not need a full axillary lymph node dissection. In contrast, if the SLN is positive, there is a good chance that other nodes will contain tumor cells, and a full ALND is usually performed.
Sentinel node biopsy is only appropriate for women who do not have evidence or suspicion of involved lymph nodes on physical examination. In such cases, a full axillary dissection is needed.
Guidelines from the American Society of Clinical Oncology recommend against the routine use of sentinel node biopsy for large breast cancers (>5 cm), tumors that are fixed or attached to the skin or chest wall, and inflammatory breast cancers [1]. This recommendation was largely based upon the lack of published studies in these groups of women. However, many clinicians feel that SLN biopsy is an acceptable way of assessing the status of the axillary lymph nodes in patients with a large breast cancer (> 5 cm) who do not have enlarged axillary lymph nodes on physical examination, as long as the tumor is not fixed to the skin or underlying chest wall and there is no inflammatory component.
For patients who undergo a sentinel node biopsy for LABC, the timing of the procedure is also controversial; there is no consensus as to the best approach. Most clinicians (including the authors) perform SLN biopsy prior to beginning therapy for the LABC in order to guide later management of the axillary nodes. If the SLN is negative, a full ALND is not performed at the time of surgery, and instead the axilla is radiated. If the SLN is positive, a full ALND is done at the time of surgery.
TREATMENT OF LOCALLY ADVANCED BREAST CANCER — LABC is most often treated with combined chemotherapy, surgery, and radiation therapy. Another term for combination treatment such as this is multimodality therapy. Studies suggest that when a combined approach is used, approximately 50 percent of women with LABC will be long-term survivors and possibly cured of their breast cancer.
Chemotherapy — Chemotherapy refers to the use of medicines to stop or slow the growth of cancer cells. Chemotherapy works by interfering with the ability of rapidly growing cells (like cancer cells) to divide or reproduce themselves. Because most of an adult's normal cells are not actively growing, they are not affected by chemotherapy, with the exception of bone marrow (where the blood cells are produced), the hair, and the lining of the gastrointestinal tract. Temporary effects of chemotherapy on these and other normal tissues cause the majority of side effects during treatment.
In most cases, chemotherapy includes a combination of two or more drugs, most often given intravenously (IV). These combinations are referred to as regimens. The drugs themselves are usually not administered daily but periodically, in cycles. A cycle of chemotherapy refers to the time it takes to administer the individual drug components of each regimen and then allow the body to recover from the effects of the medicines. A cycle of chemotherapy typically ranges from two to four weeks.
Preoperative chemotherapy — For most women with LABC, chemotherapy is the first component of the treatment. It is given before surgery is performed to remove the breast tumor. Preoperative (also called neoadjuvant) chemotherapy can successfully shrink the breast tumor, and in as many as one-third of cases, it completely removes all traces of the cancer from the breast and lymph nodes. This is termed a complete clinical response. Successful shrinkage of a large breast tumor can increase a woman's options for subsequent surgery. As an example, it might allow selected women to consider breast conserving surgery in which only the tumor is removed (lumpectomy) rather than total removal of the breast (mastectomy). (See "Surgery and radiation therapy" below).
The type of chemotherapy and the duration of treatment before surgery is variable. No one particular chemotherapy regimen has been shown to be best for treatment of LABC. A typical treatment course might include four cycles of a chemotherapy combination containing an anthracycline (eg, doxorubicin) followed by four cycles of a regimen containing taxanes (eg, paclitaxel or docetaxel). Although the entire course of chemotherapy is often administered prior to surgery, it may be divided between the preoperative and postoperative periods.
Hormone therapy — As noted above, breast cancers that produce hormone receptors are responsive to hormone therapy. In some cases, hormone therapy may be used instead of chemotherapy as the initial treatment for a LABC.
Preoperative hormone therapy — The preoperative (neoadjuvant) use of hormone therapy can successfully shrink breast cancers that are hormone-responsive. However, the likelihood of achieving a complete clinical response seems to be lower than that found with chemotherapy. Because hormone therapy is generally better tolerated than chemotherapy (and can be given by mouth rather than intravenously), it may be recommended for elderly women whose organ function is impaired, patients who want to avoid chemotherapy-related toxicity, or those who are physically debilitated.
Postoperative (adjuvant) hormone therapy — For most women with hormone-responsive LABC, hormone therapy is usually recommended after surgery for five or more years. When hormone therapy (or chemotherapy) is given after surgery, it is referred to as adjuvant therapy, and its purpose is to eliminate any tumor cells that remain in the body (often termed micrometastases) following surgery.
Adjuvant hormone therapy is usually started after the entire course of chemotherapy is finished because of concerns that the two treatments will counteract each other if given together. However, hormone therapy can be started during the radiation treatment.
Trastuzumab (Herceptin®) — Trastuzumab (Herceptin) is a unique drug that works by a different mechanism than chemotherapy. It is an antibody that specifically targets a protein called HER2, which is present on the cells of some breast cancers. About 20 percent of breast cancers express very high levels of this marker, and trastuzumab appears to be effective only in this group of women (see "HER2 expression" above).
Interest in using trastuzumab in women with LABC has increased because of information that suggests that adding trastuzumab to chemotherapy in women with earlier stage (stage II) breast cancers that produce high levels of the protein HER2 improves their chances of surviving their breast cancer. (See "Patient information: Adjuvant chemotherapy and trastuzumab (Herceptin) for early stage breast cancer").
Initial reports of neoadjuvant trastuzumab treatment are encouraging [6]. However, this approach is still considered investigational since data on long-term outcome and safety are lacking. In addition, the best way to incorporate trastuzumab into neoadjuvant chemotherapy for women with LABC is unknown.
Surgery and radiation therapy — Following chemotherapy, tests are performed to assess how the tumor responded to treatment. A physical examination and repeat imaging studies (using mammography, breast ultrasound, or MRI) are conducted to measure the extent of disease that remains in the breast and regional lymph nodes. Breast surgery may then be performed.
Breast-conserving surgery (such as a lumpectomy) is an option for many women with LABC, as long as they do not have inflammatory breast cancer (see "Inflammatory breast cancer" belowsee "Inflammatory breast cancer" below). Mastectomy (total removal of the breast) is necessary if skin involvement has not regressed following chemotherapy or if the tumor is still fixed to the underlying chest wall (show figure 1).
After surgery, radiation therapy to the remaining breast tissue (on the side where the tumor was located) is necessary for women who have undergone breast conserving therapy. This substantially decreases the chance that the tumor will return or recur in the remaining breast tissue.
In addition, chest wall radiation therapy may be recommended to women who have undergone a mastectomy, particularly if they have a large number of involved axillary lymph nodes or inflammatory breast cancer. Studies show that using both surgery and radiation therapy decreases the chance that the breast cancer will return (recur) locally in the breast or the chest wall.
INFLAMMATORY BREAST CANCER — The treatment of inflammatory breast cancer is similar to that of other types of LABC. Multimodality therapy involving chemotherapy, surgery, and radiation therapy is generally recommended as it is associated with the best outcomes. As with other forms of LABC, two types of chemotherapy agents (anthracyclines and a taxane) are usually used.
One difference in the treatment of IBC is that mastectomy is usually recommended, rather than breast-conserving surgery, even if there was a good response to neoadjuvant chemotherapy. Following mastectomy, chest wall and regional lymph node radiation therapy is strongly recommended as a part of postoperative management.
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Cancer Institute
1-800-4-CANCER
(www.nci.nih.gov)
People Living With Cancer: The official patient information
website of the American Society of Clinical Oncology
(http://breastca.asco.org)
National Comprehensive Cancer Network
(www.nccn.org/patients/patient_gls.asp)
American Cancer Society
1-800-ACS-2345
(www.cancer.org)
National Library of Medicine
(www.nlm.nih.gov/medlineplus)
Susan G. Komen Breast Cancer Foundation
(www.komen.org)
[1-10]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Lyman, GH, Giuliano, AE, Somerfield, MR, et al. American Society of Clinical Oncology Guideline Recommendations for Sentinel Lymph Node Biopsy in Early-Stage Breast Cancer. J Clin Oncol 2005; 23:7703.
2. Schwartz, GF, Hortobagyi, GN. Proceedings of the consensus conference on neoadjuvant chemotherapy in carcinoma of the breast, April 26-28, 2003, Philadelphia, Pennsylvania. Cancer 2004; 100:2512.
3. Kaufmann, M, von Minckwitz, G, Smith, R, et al. International expert panel on the use of primary (preoperative) systemic treatment of operable breast cancer: review and recommendations. J Clin Oncol 2003; 21:2600.
4. Bear, HD, Anderson, S, Brown, A, et al. The effect of tumor response of adding sequential preoperative docetaxel to preoperative doxorubicin and cyclophosphamide: preliminary results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol 2003; 21:4165.
5. Hoff, PM, Valero, V, Buzdar, AU, et al. Combined modality treatment of locally advanced breast carcinoma in elderly patients or patients with severe comorbid conditions using tamoxifen as the primary therapy. Cancer 2000; 88:2054.
6. Burstein, HJ, Harris, LN, Gelman, R, et al. Preoperative Therapy With Trastuzumab and Paclitaxel Followed by Sequential Adjuvant Doxorubicin/Cyclophosphamide for HER2 Overexpressing Stage II or III Breast Cancer: A Pilot Study. J Clin Oncol 2003; 21:46.
7. Singletary, SE, McNeese, MD, Hortobagyi, GN. Feasibility of breast-conservation surgery after induction chemotherapy for locally advanced breast carcinoma. Cancer 1992; 69:2849.
8. Huang, EH, Tucker, SL, Strom, EA, et al. Postmastectomy radiation improves local-regional control and survival for selected patients with locally advanced breast cancer treated with neoadjuvant chemotherapy and mastectomy. J Clin Oncol 2004; 22:4639.
9. Harris, EE, Schultz, D, Bertsch, H, et al. Ten-year outcome after combined modality therapy for inflammatory breast cancer. Int J Radiat Oncol Biol Phys 2003; 55:1200.
10. Cristofanilli, M, Gonzalez-Angulo, AM, Buzdar, AU, et al. Paclitaxel improves the prognosis in estrogen receptor negative inflammatory breast cancer: the M. D. Anderson Cancer Center experience. Clin Breast Cancer 2004; 4:415.
Friday, October 12, 2007
Locally advanced and inflammatory breast cancer
INTRODUCTION — Breast cancer is the most common female cancer in the United States, the second most common cause of cancer death in women (after lung cancer), and the primary cause of death in women ages 45 to 55. Early detection and treatment can often lead to a cure. Cure is most likely in women whose breast cancers are confined to the breast, while a substantial number of women whose tumors have spread to the local lymph nodes in the armpit (also called the axilla) can also be cured with appropriate therapy.
Occasionally, a breast cancer will not be discovered until it is fairly large or locally advanced. The term locally advanced breast cancer (LABC) is used to describe a breast cancer that has progressed locally but has not yet spread beyond the breast and regional lymph nodes. LABC includes large breast tumors (more than 5 centimeters in diameter), those that involve the skin of the breast or the underlying muscles of the chest wall, and cancers that have extensive involvement of the regional lymph nodes (those located in the axilla or in the soft tissues above and below the collarbone). It also includes inflammatory breast cancer, a rapidly growing type of cancer that makes the breast appear red and swollen (hence the term inflammatory).
Although the likelihood of curing LABC is lower than it would be if the cancer were small and confined to the breast, cure is possible with aggressive treatment. In most cases, this requires a combination of chemotherapy, radiation therapy, and surgery.
This topic review will cover the treatment of locally advanced breast cancer, including inflammatory breast cancer. Breast cancer is a very complex topic. An introduction to breast cancer and an overview of available treatments is available elsewhere. (See "Patient information: Breast cancer guide to diagnosis and treatment").
SIGNS AND SYMPTOMS
Locally advanced breast cancer (LABC) — Most LABCs can be felt (palpated) by both the patient and her doctor; they may also be visible. A careful physical examination of the breasts, skin of the chest, and regional lymph nodes (in the axilla and above the collarbone) is the first step in evaluation.
LABC is suspected if the tumor measures more than 5 cm across, or if it is fixed or attached to the underlying muscles or overlying skin of the chest wall. The finding of skin nodules on the affected breast, lymph nodes above or below the collarbone (called supraclavicular and infraclavicular nodes), or axillary lymph nodes that are non-movable and either attached to the underlying tissues (fixed) or to each other (matted) also suggests LABC.
Inflammatory breast cancer — Inflammatory breast cancer (IBC) is a specific type of LABC which produces a unique set of symptoms. IBC often does not produce a distinct mass or lump that can be felt within the breast. Instead, it causes thickening and swelling of the skin of the breast, which may be reddened and warm to the touch (show picture 1 and show picture 2). The breast is often painful and enlarged, and appears inflamed.
IBC may initially be confused with other inflammatory breast conditions, particularly infections. For example, women who are breastfeeding may develop a breast abscess or mastitis, which can produce symptoms similar to IBC. However, these conditions are usually associated with a fever and other evidence of infection (such as an increase in the number of white blood cells) that distinguish them from IBC.
DIAGNOSIS AND STAGING — Once the diagnosis of a breast cancer is suspected, several procedures must be done to confirm the diagnosis and establish the extent of tumor involvement, both within the breast and elsewhere in the body.
Mammogram — A mammogram of both breasts is needed to visualize the extent of tumor involvement within the breast and to make certain that the opposite breast is unaffected. Other tests such as a breast magnetic resonance imaging (MRI) study or ultrasound may be recommended (show radiograph 1).
Biopsy of the tumor — In order to confirm the diagnosis and type of breast cancer, a biopsy is required. A needle biopsy of the tumor, performed in the office, is usually sufficient to obtain enough tissue for the pathologist to study under the microscope.
The pathologist will also perform other tests to determine if the tumor is making hormone receptors and a protein called Her2 (also called erbB-2). These two factors are important in selecting the best treatment.
Hormone receptors — About 50 to 70 percent of breast cancers require the female hormone estrogen (estradiol) to grow; other breast cancers are able to grow without estrogen. Estrogen-dependent breast cancer cells produce molecules called hormone receptors, which are essential for the cell to use estrogen for growth. These hormone receptors can be estrogen receptors (ER), progesterone receptors (PR), or both.
If hormone receptors are present within a breast cancer, women are significantly more likely to benefit from treatments that lower estrogen levels or block the actions of estrogen, thus depriving the cancer cells of the material that stimulates their growth. These treatments are referred to as endocrine or hormone therapies, and such tumors are referred to as "hormone-responsive". In contrast, women whose tumors do not contain any ER or PR do not benefit from adjuvant hormone therapy.
HER2 expression — HER2 is a protein that is present on about one-third of breast tumors. The finding of HER2 within an individual breast cancer is an important indicator of benefit from a drug called trastuzumab (See "Trastuzumab (Herceptin®)" below).
Staging workup — Once the diagnosis of breast cancer is established, additional studies are performed to stage the cancer (determine how far it has spread). The stage of a breast cancer is based upon tumor size, involvement of the skin, chest wall or regional lymph nodes, and whether the cancer has spread to the bones or other organs (called metastasis).
The following studies may be recommended to search for evidence of spread to other organs: Blood tests, including a complete blood count and liver function tests Bone scan Chest X-ray or CT scan CT scan of the abdomen and pelvis CT scan or magnetic resonance imaging (MRI) of the brain A PET scan
After a complete evaluation, the size and extent of the breast tumor, type and extent of lymph node involvement, and the presence or absence of spread to other organs are grouped together to form the stage grouping of a breast cancer, which ranges from stage I to IV. A description of each stage is provided in table 1 (show table 1) Locally advanced breast cancer is stage III disease, and the presence of IBC makes the cancer a stage IIIB cancer
In contrast, women who have stage I or II breast cancer are referred to as having early stage disease, while stage IV means that spread to other organs has taken place.
Staging the axilla — The majority of patients with LABC have lymph nodes or glands that can be felt or palpated in the axilla by their physician. For the minority who do not have palpable axillary nodes, formal assessment of these nodes is often considered before beginning therapy. Knowing if the lymph nodes in the axilla are involved with the cancer can influence the choice of therapy. Surgery to remove some or all of these lymph nodes is the only accurate way to determine if the cancer has spread to the axillary lymph nodes.
Complete removal of the axillary lymph nodes (called axillary lymph node dissection or ALND), has traditionally been a routine component of the management of breast cancer. However, one of the most feared complications of ALND is swelling of the arm (called arm edema), the severity of which depends on the extent of the ALND and the use radiation therapy of the axilla. Thee need to accurately identify women who have involved lymph nodes while minimizing the chance of arm swelling led to the development of the sentinel node biopsy technique. (See "Patient information: Lymphedema after breast cancer surgery").
Sentinel node biopsy — The sentinel lymph node (SLN) concept is based on the premise that tumor cells that have broken off from a breast tumor first involve one or a few lymph nodes before involving other nodes or spreading elsewhere. To identify this node, the surgeon injects dye, a radioactive material, or a combination of both into the area surrounding the tumor, where it enters lymphatic channels and then flows to lymph nodes. If an SLN is identified, it is removed and examined under the microscope. If this node is negative, the chance of the other axillary nodes being also negative is good, and such women may not need a full axillary lymph node dissection. In contrast, if the SLN is positive, there is a good chance that other nodes will contain tumor cells, and a full ALND is usually performed.
Sentinel node biopsy is only appropriate for women who do not have evidence or suspicion of involved lymph nodes on physical examination. In such cases, a full axillary dissection is needed.
Guidelines from the American Society of Clinical Oncology recommend against the routine use of sentinel node biopsy for large breast cancers (>5 cm), tumors that are fixed or attached to the skin or chest wall, and inflammatory breast cancers [1]. This recommendation was largely based upon the lack of published studies in these groups of women. However, many clinicians feel that SLN biopsy is an acceptable way of assessing the status of the axillary lymph nodes in patients with a large breast cancer (> 5 cm) who do not have enlarged axillary lymph nodes on physical examination, as long as the tumor is not fixed to the skin or underlying chest wall and there is no inflammatory component.
For patients who undergo a sentinel node biopsy for LABC, the timing of the procedure is also controversial; there is no consensus as to the best approach. Most clinicians (including the authors) perform SLN biopsy prior to beginning therapy for the LABC in order to guide later management of the axillary nodes. If the SLN is negative, a full ALND is not performed at the time of surgery, and instead the axilla is radiated. If the SLN is positive, a full ALND is done at the time of surgery.
TREATMENT OF LOCALLY ADVANCED BREAST CANCER — LABC is most often treated with combined chemotherapy, surgery, and radiation therapy. Another term for combination treatment such as this is multimodality therapy. Studies suggest that when a combined approach is used, approximately 50 percent of women with LABC will be long-term survivors and possibly cured of their breast cancer.
Chemotherapy — Chemotherapy refers to the use of medicines to stop or slow the growth of cancer cells. Chemotherapy works by interfering with the ability of rapidly growing cells (like cancer cells) to divide or reproduce themselves. Because most of an adult's normal cells are not actively growing, they are not affected by chemotherapy, with the exception of bone marrow (where the blood cells are produced), the hair, and the lining of the gastrointestinal tract. Temporary effects of chemotherapy on these and other normal tissues cause the majority of side effects during treatment.
In most cases, chemotherapy includes a combination of two or more drugs, most often given intravenously (IV). These combinations are referred to as regimens. The drugs themselves are usually not administered daily but periodically, in cycles. A cycle of chemotherapy refers to the time it takes to administer the individual drug components of each regimen and then allow the body to recover from the effects of the medicines. A cycle of chemotherapy typically ranges from two to four weeks.
Preoperative chemotherapy — For most women with LABC, chemotherapy is the first component of the treatment. It is given before surgery is performed to remove the breast tumor. Preoperative (also called neoadjuvant) chemotherapy can successfully shrink the breast tumor, and in as many as one-third of cases, it completely removes all traces of the cancer from the breast and lymph nodes. This is termed a complete clinical response. Successful shrinkage of a large breast tumor can increase a woman's options for subsequent surgery. As an example, it might allow selected women to consider breast conserving surgery in which only the tumor is removed (lumpectomy) rather than total removal of the breast (mastectomy). (See "Surgery and radiation therapy" below).
The type of chemotherapy and the duration of treatment before surgery is variable. No one particular chemotherapy regimen has been shown to be best for treatment of LABC. A typical treatment course might include four cycles of a chemotherapy combination containing an anthracycline (eg, doxorubicin) followed by four cycles of a regimen containing taxanes (eg, paclitaxel or docetaxel). Although the entire course of chemotherapy is often administered prior to surgery, it may be divided between the preoperative and postoperative periods.
Hormone therapy — As noted above, breast cancers that produce hormone receptors are responsive to hormone therapy. In some cases, hormone therapy may be used instead of chemotherapy as the initial treatment for a LABC.
Preoperative hormone therapy — The preoperative (neoadjuvant) use of hormone therapy can successfully shrink breast cancers that are hormone-responsive. However, the likelihood of achieving a complete clinical response seems to be lower than that found with chemotherapy. Because hormone therapy is generally better tolerated than chemotherapy (and can be given by mouth rather than intravenously), it may be recommended for elderly women whose organ function is impaired, patients who want to avoid chemotherapy-related toxicity, or those who are physically debilitated.
Postoperative (adjuvant) hormone therapy — For most women with hormone-responsive LABC, hormone therapy is usually recommended after surgery for five or more years. When hormone therapy (or chemotherapy) is given after surgery, it is referred to as adjuvant therapy, and its purpose is to eliminate any tumor cells that remain in the body (often termed micrometastases) following surgery.
Adjuvant hormone therapy is usually started after the entire course of chemotherapy is finished because of concerns that the two treatments will counteract each other if given together. However, hormone therapy can be started during the radiation treatment.
Trastuzumab (Herceptin®) — Trastuzumab (Herceptin) is a unique drug that works by a different mechanism than chemotherapy. It is an antibody that specifically targets a protein called HER2, which is present on the cells of some breast cancers. About 20 percent of breast cancers express very high levels of this marker, and trastuzumab appears to be effective only in this group of women (see "HER2 expression" above).
Interest in using trastuzumab in women with LABC has increased because of information that suggests that adding trastuzumab to chemotherapy in women with earlier stage (stage II) breast cancers that produce high levels of the protein HER2 improves their chances of surviving their breast cancer. (See "Patient information: Adjuvant chemotherapy and trastuzumab (Herceptin) for early stage breast cancer").
Initial reports of neoadjuvant trastuzumab treatment are encouraging [6]. However, this approach is still considered investigational since data on long-term outcome and safety are lacking. In addition, the best way to incorporate trastuzumab into neoadjuvant chemotherapy for women with LABC is unknown.
Surgery and radiation therapy — Following chemotherapy, tests are performed to assess how the tumor responded to treatment. A physical examination and repeat imaging studies (using mammography, breast ultrasound, or MRI) are conducted to measure the extent of disease that remains in the breast and regional lymph nodes. Breast surgery may then be performed.
Breast-conserving surgery (such as a lumpectomy) is an option for many women with LABC, as long as they do not have inflammatory breast cancer (see "Inflammatory breast cancer" belowsee "Inflammatory breast cancer" below). Mastectomy (total removal of the breast) is necessary if skin involvement has not regressed following chemotherapy or if the tumor is still fixed to the underlying chest wall (show figure 1).
After surgery, radiation therapy to the remaining breast tissue (on the side where the tumor was located) is necessary for women who have undergone breast conserving therapy. This substantially decreases the chance that the tumor will return or recur in the remaining breast tissue.
In addition, chest wall radiation therapy may be recommended to women who have undergone a mastectomy, particularly if they have a large number of involved axillary lymph nodes or inflammatory breast cancer. Studies show that using both surgery and radiation therapy decreases the chance that the breast cancer will return (recur) locally in the breast or the chest wall.
INFLAMMATORY BREAST CANCER — The treatment of inflammatory breast cancer is similar to that of other types of LABC. Multimodality therapy involving chemotherapy, surgery, and radiation therapy is generally recommended as it is associated with the best outcomes. As with other forms of LABC, two types of chemotherapy agents (anthracyclines and a taxane) are usually used.
One difference in the treatment of IBC is that mastectomy is usually recommended, rather than breast-conserving surgery, even if there was a good response to neoadjuvant chemotherapy. Following mastectomy, chest wall and regional lymph node radiation therapy is strongly recommended as a part of postoperative management.
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Cancer Institute
1-800-4-CANCER
(www.nci.nih.gov)
People Living With Cancer: The official patient information
website of the American Society of Clinical Oncology
(http://breastca.asco.org)
National Comprehensive Cancer Network
(www.nccn.org/patients/patient_gls.asp)
American Cancer Society
1-800-ACS-2345
(www.cancer.org)
National Library of Medicine
(www.nlm.nih.gov/medlineplus)
Susan G. Komen Breast Cancer Foundation
(www.komen.org)
[1-10]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Lyman, GH, Giuliano, AE, Somerfield, MR, et al. American Society of Clinical Oncology Guideline Recommendations for Sentinel Lymph Node Biopsy in Early-Stage Breast Cancer. J Clin Oncol 2005; 23:7703.
2. Schwartz, GF, Hortobagyi, GN. Proceedings of the consensus conference on neoadjuvant chemotherapy in carcinoma of the breast, April 26-28, 2003, Philadelphia, Pennsylvania. Cancer 2004; 100:2512.
3. Kaufmann, M, von Minckwitz, G, Smith, R, et al. International expert panel on the use of primary (preoperative) systemic treatment of operable breast cancer: review and recommendations. J Clin Oncol 2003; 21:2600.
4. Bear, HD, Anderson, S, Brown, A, et al. The effect of tumor response of adding sequential preoperative docetaxel to preoperative doxorubicin and cyclophosphamide: preliminary results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol 2003; 21:4165.
5. Hoff, PM, Valero, V, Buzdar, AU, et al. Combined modality treatment of locally advanced breast carcinoma in elderly patients or patients with severe comorbid conditions using tamoxifen as the primary therapy. Cancer 2000; 88:2054.
6. Burstein, HJ, Harris, LN, Gelman, R, et al. Preoperative Therapy With Trastuzumab and Paclitaxel Followed by Sequential Adjuvant Doxorubicin/Cyclophosphamide for HER2 Overexpressing Stage II or III Breast Cancer: A Pilot Study. J Clin Oncol 2003; 21:46.
7. Singletary, SE, McNeese, MD, Hortobagyi, GN. Feasibility of breast-conservation surgery after induction chemotherapy for locally advanced breast carcinoma. Cancer 1992; 69:2849.
8. Huang, EH, Tucker, SL, Strom, EA, et al. Postmastectomy radiation improves local-regional control and survival for selected patients with locally advanced breast cancer treated with neoadjuvant chemotherapy and mastectomy. J Clin Oncol 2004; 22:4639.
9. Harris, EE, Schultz, D, Bertsch, H, et al. Ten-year outcome after combined modality therapy for inflammatory breast cancer. Int J Radiat Oncol Biol Phys 2003; 55:1200.
10. Cristofanilli, M, Gonzalez-Angulo, AM, Buzdar, AU, et al. Paclitaxel improves the prognosis in estrogen receptor negative inflammatory breast cancer: the M. D. Anderson Cancer Center experience. Clin Breast Cancer 2004; 4:415.
Occasionally, a breast cancer will not be discovered until it is fairly large or locally advanced. The term locally advanced breast cancer (LABC) is used to describe a breast cancer that has progressed locally but has not yet spread beyond the breast and regional lymph nodes. LABC includes large breast tumors (more than 5 centimeters in diameter), those that involve the skin of the breast or the underlying muscles of the chest wall, and cancers that have extensive involvement of the regional lymph nodes (those located in the axilla or in the soft tissues above and below the collarbone). It also includes inflammatory breast cancer, a rapidly growing type of cancer that makes the breast appear red and swollen (hence the term inflammatory).
Although the likelihood of curing LABC is lower than it would be if the cancer were small and confined to the breast, cure is possible with aggressive treatment. In most cases, this requires a combination of chemotherapy, radiation therapy, and surgery.
This topic review will cover the treatment of locally advanced breast cancer, including inflammatory breast cancer. Breast cancer is a very complex topic. An introduction to breast cancer and an overview of available treatments is available elsewhere. (See "Patient information: Breast cancer guide to diagnosis and treatment").
SIGNS AND SYMPTOMS
Locally advanced breast cancer (LABC) — Most LABCs can be felt (palpated) by both the patient and her doctor; they may also be visible. A careful physical examination of the breasts, skin of the chest, and regional lymph nodes (in the axilla and above the collarbone) is the first step in evaluation.
LABC is suspected if the tumor measures more than 5 cm across, or if it is fixed or attached to the underlying muscles or overlying skin of the chest wall. The finding of skin nodules on the affected breast, lymph nodes above or below the collarbone (called supraclavicular and infraclavicular nodes), or axillary lymph nodes that are non-movable and either attached to the underlying tissues (fixed) or to each other (matted) also suggests LABC.
Inflammatory breast cancer — Inflammatory breast cancer (IBC) is a specific type of LABC which produces a unique set of symptoms. IBC often does not produce a distinct mass or lump that can be felt within the breast. Instead, it causes thickening and swelling of the skin of the breast, which may be reddened and warm to the touch (show picture 1 and show picture 2). The breast is often painful and enlarged, and appears inflamed.
IBC may initially be confused with other inflammatory breast conditions, particularly infections. For example, women who are breastfeeding may develop a breast abscess or mastitis, which can produce symptoms similar to IBC. However, these conditions are usually associated with a fever and other evidence of infection (such as an increase in the number of white blood cells) that distinguish them from IBC.
DIAGNOSIS AND STAGING — Once the diagnosis of a breast cancer is suspected, several procedures must be done to confirm the diagnosis and establish the extent of tumor involvement, both within the breast and elsewhere in the body.
Mammogram — A mammogram of both breasts is needed to visualize the extent of tumor involvement within the breast and to make certain that the opposite breast is unaffected. Other tests such as a breast magnetic resonance imaging (MRI) study or ultrasound may be recommended (show radiograph 1).
Biopsy of the tumor — In order to confirm the diagnosis and type of breast cancer, a biopsy is required. A needle biopsy of the tumor, performed in the office, is usually sufficient to obtain enough tissue for the pathologist to study under the microscope.
The pathologist will also perform other tests to determine if the tumor is making hormone receptors and a protein called Her2 (also called erbB-2). These two factors are important in selecting the best treatment.
Hormone receptors — About 50 to 70 percent of breast cancers require the female hormone estrogen (estradiol) to grow; other breast cancers are able to grow without estrogen. Estrogen-dependent breast cancer cells produce molecules called hormone receptors, which are essential for the cell to use estrogen for growth. These hormone receptors can be estrogen receptors (ER), progesterone receptors (PR), or both.
If hormone receptors are present within a breast cancer, women are significantly more likely to benefit from treatments that lower estrogen levels or block the actions of estrogen, thus depriving the cancer cells of the material that stimulates their growth. These treatments are referred to as endocrine or hormone therapies, and such tumors are referred to as "hormone-responsive". In contrast, women whose tumors do not contain any ER or PR do not benefit from adjuvant hormone therapy.
HER2 expression — HER2 is a protein that is present on about one-third of breast tumors. The finding of HER2 within an individual breast cancer is an important indicator of benefit from a drug called trastuzumab (See "Trastuzumab (Herceptin®)" below).
Staging workup — Once the diagnosis of breast cancer is established, additional studies are performed to stage the cancer (determine how far it has spread). The stage of a breast cancer is based upon tumor size, involvement of the skin, chest wall or regional lymph nodes, and whether the cancer has spread to the bones or other organs (called metastasis).
The following studies may be recommended to search for evidence of spread to other organs: Blood tests, including a complete blood count and liver function tests Bone scan Chest X-ray or CT scan CT scan of the abdomen and pelvis CT scan or magnetic resonance imaging (MRI) of the brain A PET scan
After a complete evaluation, the size and extent of the breast tumor, type and extent of lymph node involvement, and the presence or absence of spread to other organs are grouped together to form the stage grouping of a breast cancer, which ranges from stage I to IV. A description of each stage is provided in table 1 (show table 1) Locally advanced breast cancer is stage III disease, and the presence of IBC makes the cancer a stage IIIB cancer
In contrast, women who have stage I or II breast cancer are referred to as having early stage disease, while stage IV means that spread to other organs has taken place.
Staging the axilla — The majority of patients with LABC have lymph nodes or glands that can be felt or palpated in the axilla by their physician. For the minority who do not have palpable axillary nodes, formal assessment of these nodes is often considered before beginning therapy. Knowing if the lymph nodes in the axilla are involved with the cancer can influence the choice of therapy. Surgery to remove some or all of these lymph nodes is the only accurate way to determine if the cancer has spread to the axillary lymph nodes.
Complete removal of the axillary lymph nodes (called axillary lymph node dissection or ALND), has traditionally been a routine component of the management of breast cancer. However, one of the most feared complications of ALND is swelling of the arm (called arm edema), the severity of which depends on the extent of the ALND and the use radiation therapy of the axilla. Thee need to accurately identify women who have involved lymph nodes while minimizing the chance of arm swelling led to the development of the sentinel node biopsy technique. (See "Patient information: Lymphedema after breast cancer surgery").
Sentinel node biopsy — The sentinel lymph node (SLN) concept is based on the premise that tumor cells that have broken off from a breast tumor first involve one or a few lymph nodes before involving other nodes or spreading elsewhere. To identify this node, the surgeon injects dye, a radioactive material, or a combination of both into the area surrounding the tumor, where it enters lymphatic channels and then flows to lymph nodes. If an SLN is identified, it is removed and examined under the microscope. If this node is negative, the chance of the other axillary nodes being also negative is good, and such women may not need a full axillary lymph node dissection. In contrast, if the SLN is positive, there is a good chance that other nodes will contain tumor cells, and a full ALND is usually performed.
Sentinel node biopsy is only appropriate for women who do not have evidence or suspicion of involved lymph nodes on physical examination. In such cases, a full axillary dissection is needed.
Guidelines from the American Society of Clinical Oncology recommend against the routine use of sentinel node biopsy for large breast cancers (>5 cm), tumors that are fixed or attached to the skin or chest wall, and inflammatory breast cancers [1]. This recommendation was largely based upon the lack of published studies in these groups of women. However, many clinicians feel that SLN biopsy is an acceptable way of assessing the status of the axillary lymph nodes in patients with a large breast cancer (> 5 cm) who do not have enlarged axillary lymph nodes on physical examination, as long as the tumor is not fixed to the skin or underlying chest wall and there is no inflammatory component.
For patients who undergo a sentinel node biopsy for LABC, the timing of the procedure is also controversial; there is no consensus as to the best approach. Most clinicians (including the authors) perform SLN biopsy prior to beginning therapy for the LABC in order to guide later management of the axillary nodes. If the SLN is negative, a full ALND is not performed at the time of surgery, and instead the axilla is radiated. If the SLN is positive, a full ALND is done at the time of surgery.
TREATMENT OF LOCALLY ADVANCED BREAST CANCER — LABC is most often treated with combined chemotherapy, surgery, and radiation therapy. Another term for combination treatment such as this is multimodality therapy. Studies suggest that when a combined approach is used, approximately 50 percent of women with LABC will be long-term survivors and possibly cured of their breast cancer.
Chemotherapy — Chemotherapy refers to the use of medicines to stop or slow the growth of cancer cells. Chemotherapy works by interfering with the ability of rapidly growing cells (like cancer cells) to divide or reproduce themselves. Because most of an adult's normal cells are not actively growing, they are not affected by chemotherapy, with the exception of bone marrow (where the blood cells are produced), the hair, and the lining of the gastrointestinal tract. Temporary effects of chemotherapy on these and other normal tissues cause the majority of side effects during treatment.
In most cases, chemotherapy includes a combination of two or more drugs, most often given intravenously (IV). These combinations are referred to as regimens. The drugs themselves are usually not administered daily but periodically, in cycles. A cycle of chemotherapy refers to the time it takes to administer the individual drug components of each regimen and then allow the body to recover from the effects of the medicines. A cycle of chemotherapy typically ranges from two to four weeks.
Preoperative chemotherapy — For most women with LABC, chemotherapy is the first component of the treatment. It is given before surgery is performed to remove the breast tumor. Preoperative (also called neoadjuvant) chemotherapy can successfully shrink the breast tumor, and in as many as one-third of cases, it completely removes all traces of the cancer from the breast and lymph nodes. This is termed a complete clinical response. Successful shrinkage of a large breast tumor can increase a woman's options for subsequent surgery. As an example, it might allow selected women to consider breast conserving surgery in which only the tumor is removed (lumpectomy) rather than total removal of the breast (mastectomy). (See "Surgery and radiation therapy" below).
The type of chemotherapy and the duration of treatment before surgery is variable. No one particular chemotherapy regimen has been shown to be best for treatment of LABC. A typical treatment course might include four cycles of a chemotherapy combination containing an anthracycline (eg, doxorubicin) followed by four cycles of a regimen containing taxanes (eg, paclitaxel or docetaxel). Although the entire course of chemotherapy is often administered prior to surgery, it may be divided between the preoperative and postoperative periods.
Hormone therapy — As noted above, breast cancers that produce hormone receptors are responsive to hormone therapy. In some cases, hormone therapy may be used instead of chemotherapy as the initial treatment for a LABC.
Preoperative hormone therapy — The preoperative (neoadjuvant) use of hormone therapy can successfully shrink breast cancers that are hormone-responsive. However, the likelihood of achieving a complete clinical response seems to be lower than that found with chemotherapy. Because hormone therapy is generally better tolerated than chemotherapy (and can be given by mouth rather than intravenously), it may be recommended for elderly women whose organ function is impaired, patients who want to avoid chemotherapy-related toxicity, or those who are physically debilitated.
Postoperative (adjuvant) hormone therapy — For most women with hormone-responsive LABC, hormone therapy is usually recommended after surgery for five or more years. When hormone therapy (or chemotherapy) is given after surgery, it is referred to as adjuvant therapy, and its purpose is to eliminate any tumor cells that remain in the body (often termed micrometastases) following surgery.
Adjuvant hormone therapy is usually started after the entire course of chemotherapy is finished because of concerns that the two treatments will counteract each other if given together. However, hormone therapy can be started during the radiation treatment.
Trastuzumab (Herceptin®) — Trastuzumab (Herceptin) is a unique drug that works by a different mechanism than chemotherapy. It is an antibody that specifically targets a protein called HER2, which is present on the cells of some breast cancers. About 20 percent of breast cancers express very high levels of this marker, and trastuzumab appears to be effective only in this group of women (see "HER2 expression" above).
Interest in using trastuzumab in women with LABC has increased because of information that suggests that adding trastuzumab to chemotherapy in women with earlier stage (stage II) breast cancers that produce high levels of the protein HER2 improves their chances of surviving their breast cancer. (See "Patient information: Adjuvant chemotherapy and trastuzumab (Herceptin) for early stage breast cancer").
Initial reports of neoadjuvant trastuzumab treatment are encouraging [6]. However, this approach is still considered investigational since data on long-term outcome and safety are lacking. In addition, the best way to incorporate trastuzumab into neoadjuvant chemotherapy for women with LABC is unknown.
Surgery and radiation therapy — Following chemotherapy, tests are performed to assess how the tumor responded to treatment. A physical examination and repeat imaging studies (using mammography, breast ultrasound, or MRI) are conducted to measure the extent of disease that remains in the breast and regional lymph nodes. Breast surgery may then be performed.
Breast-conserving surgery (such as a lumpectomy) is an option for many women with LABC, as long as they do not have inflammatory breast cancer (see "Inflammatory breast cancer" belowsee "Inflammatory breast cancer" below). Mastectomy (total removal of the breast) is necessary if skin involvement has not regressed following chemotherapy or if the tumor is still fixed to the underlying chest wall (show figure 1).
After surgery, radiation therapy to the remaining breast tissue (on the side where the tumor was located) is necessary for women who have undergone breast conserving therapy. This substantially decreases the chance that the tumor will return or recur in the remaining breast tissue.
In addition, chest wall radiation therapy may be recommended to women who have undergone a mastectomy, particularly if they have a large number of involved axillary lymph nodes or inflammatory breast cancer. Studies show that using both surgery and radiation therapy decreases the chance that the breast cancer will return (recur) locally in the breast or the chest wall.
INFLAMMATORY BREAST CANCER — The treatment of inflammatory breast cancer is similar to that of other types of LABC. Multimodality therapy involving chemotherapy, surgery, and radiation therapy is generally recommended as it is associated with the best outcomes. As with other forms of LABC, two types of chemotherapy agents (anthracyclines and a taxane) are usually used.
One difference in the treatment of IBC is that mastectomy is usually recommended, rather than breast-conserving surgery, even if there was a good response to neoadjuvant chemotherapy. Following mastectomy, chest wall and regional lymph node radiation therapy is strongly recommended as a part of postoperative management.
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Cancer Institute
1-800-4-CANCER
(www.nci.nih.gov)
People Living With Cancer: The official patient information
website of the American Society of Clinical Oncology
(http://breastca.asco.org)
National Comprehensive Cancer Network
(www.nccn.org/patients/patient_gls.asp)
American Cancer Society
1-800-ACS-2345
(www.cancer.org)
National Library of Medicine
(www.nlm.nih.gov/medlineplus)
Susan G. Komen Breast Cancer Foundation
(www.komen.org)
[1-10]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Lyman, GH, Giuliano, AE, Somerfield, MR, et al. American Society of Clinical Oncology Guideline Recommendations for Sentinel Lymph Node Biopsy in Early-Stage Breast Cancer. J Clin Oncol 2005; 23:7703.
2. Schwartz, GF, Hortobagyi, GN. Proceedings of the consensus conference on neoadjuvant chemotherapy in carcinoma of the breast, April 26-28, 2003, Philadelphia, Pennsylvania. Cancer 2004; 100:2512.
3. Kaufmann, M, von Minckwitz, G, Smith, R, et al. International expert panel on the use of primary (preoperative) systemic treatment of operable breast cancer: review and recommendations. J Clin Oncol 2003; 21:2600.
4. Bear, HD, Anderson, S, Brown, A, et al. The effect of tumor response of adding sequential preoperative docetaxel to preoperative doxorubicin and cyclophosphamide: preliminary results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol 2003; 21:4165.
5. Hoff, PM, Valero, V, Buzdar, AU, et al. Combined modality treatment of locally advanced breast carcinoma in elderly patients or patients with severe comorbid conditions using tamoxifen as the primary therapy. Cancer 2000; 88:2054.
6. Burstein, HJ, Harris, LN, Gelman, R, et al. Preoperative Therapy With Trastuzumab and Paclitaxel Followed by Sequential Adjuvant Doxorubicin/Cyclophosphamide for HER2 Overexpressing Stage II or III Breast Cancer: A Pilot Study. J Clin Oncol 2003; 21:46.
7. Singletary, SE, McNeese, MD, Hortobagyi, GN. Feasibility of breast-conservation surgery after induction chemotherapy for locally advanced breast carcinoma. Cancer 1992; 69:2849.
8. Huang, EH, Tucker, SL, Strom, EA, et al. Postmastectomy radiation improves local-regional control and survival for selected patients with locally advanced breast cancer treated with neoadjuvant chemotherapy and mastectomy. J Clin Oncol 2004; 22:4639.
9. Harris, EE, Schultz, D, Bertsch, H, et al. Ten-year outcome after combined modality therapy for inflammatory breast cancer. Int J Radiat Oncol Biol Phys 2003; 55:1200.
10. Cristofanilli, M, Gonzalez-Angulo, AM, Buzdar, AU, et al. Paclitaxel improves the prognosis in estrogen receptor negative inflammatory breast cancer: the M. D. Anderson Cancer Center experience. Clin Breast Cancer 2004; 4:415.
Localized breast cancer evaluation, mastectomy, and breast conserving therapy
INTRODUCTION — Breast cancer is the most common female cancer in the United States, the second most common cause of cancer death in women (after lung cancer), and the main cause of death in women ages 45 to 55. Every year, approximately 180,000 American women will be diagnosed with breast cancer, and more than 40,000 will die from it. Early detection and treatment of breast cancer clearly improves survival, by removing the breast tumor before it has a chance to spread (metastasize).
Two surgical options are available for treating localized breast cancer: mastectomy (removal of the breast) and breast preserving therapy. After either surgery, systemic (bodywide) therapy is often recommended to decrease the likelihood that the cancer will return. The options for systemic therapy include chemotherapy, hormone therapy, or antibody therapy. (See "Patient information: Adjuvant chemotherapy and trastuzumab (Herceptin) for early stage breast cancer").
The treatment of localized breast cancer must be individualized and is based upon several factors. Optimal management requires collaboration between surgeons and physicians who specialize in radiation and medical oncology. Each woman should carefully discuss the available treatment options with her doctors to determine which is the best choice for her.
BREAST CANCER STAGING — Treatment and prognosis (outcome) depend upon the stage of the cancer, which is based upon the size of the tumor, involvement of the skin, chest wall or local lymph nodes, and whether the cancer has spread to other organs (called metastasis). In situ carcinomas (eg, ductal carcinoma in situ, lobular carcinoma in situ) are the earliest recognizable breast cancers and rarely spread beyond the breast tissue; more advanced breast cancers, which are referred to as invasive carcinomas, metastasize more often.
The size of the breast tumor, involvement of adjacent lymph nodes, and the presence or absence of spread to other organs are described by the "stage grouping" of a breast cancer, which ranges from stage I to IV. Table 1 summarizes these stages (show table 1). Localized invasive breast cancer generally refers to stage I to IIIA breast cancer. (See "TNM staging classification for breast cancer").
The initial evaluation to determine the stage of a breast cancer usually involves a physical examination, mammogram, chest X-ray, and sometimes CT scans (specialized x-rays) and/or a bone scan. An important component of the staging work-up is an evaluation of the opposite breast. Breast MRI may be recommended to screen the opposite breast for cancer in women who have a breast cancer on one side and who have no abnormalities noted within the opposite breast by either physical examination or mammogram [1,2].
The final stage of the cancer depends upon what is found during microscopic examination of the breast and lymph node tissue after surgery; this is called the pathologic stage, and it is the most accurate indicator of tumor extent and prognosis.
FACTORS AFFECTING TREATMENT — Several factors must be considered when choosing the best treatment for localized breast cancer.
Microscopic findings — There are many different varieties of breast cancer as viewed by the pathologist under the microscope. However, from the standpoint of treatment, the most important distinction is between invasive and noninvasive (in situ) breast cancer. Localized invasive breast cancers are generally approached similarly, whether they are ductal, lobular, or any of the so-called "special types" (tubular, mucinous, colloid, medullary). The surgical treatment of in situ cancers is similar to that of invasive cancers, but postoperative adjuvant systemic therapy is generally not recommended.
Size of the breast tumor — The prognosis of a breast cancer depends upon its size; larger tumors recur more often, and usually require more aggressive treatment. In some cases, chemotherapy may be given before surgery to shrink a large tumor or one that has grown into the chest wall. Inflammatory breast cancer refers to any breast cancer that is associated with an "inflamed" appearance of the breast (show picture 1 and show picture 2); this implies spread of the tumor into the lymph system of the overlying skin. These cancers are treated similarly to large tumors, with chemotherapy preceding surgery or radiation. (See "Patient information: Locally advanced and inflammatory breast cancer").
Spread of cancer cells to the lymph nodes — Fluid from the breast tissue normally drains into lymph nodes located in the armpit (the axilla). These nodes (or glands) are often the first site of spread for breast cancer. If a breast cancer has spread to lymph nodes, it is called node-positive; a cancer that has not spread to the lymph nodes is called node-negative. This is an important distinction because if a breast cancer has spread to the lymph nodes, it is twice as likely to have spread elsewhere, and therefore, to recur over the succeeding years postoperatively.
Most women with node-positive breast cancer should receive adjuvant chemotherapy or hormone therapy after surgery, even if the tumor was completely removed. (See "Patient information: Adjuvant chemotherapy and trastuzumab (Herceptin) for early stage breast cancer").
Tumor markers and prognostic factors — Studies suggest that certain markers or characteristics of the tumor may help determine the prognosis or outcome of breast cancer. Some of these tests are hormone receptors, S phase analysis (a measure of cell proliferation or growth), Her2 status. Levels of plasminogen activators (called uPA and PAI-1) are also measured in certain countries, but not routinely in the United States. All of these tests are performed on the tumor material by the pathologist.
Some of these factors may be associated with a worse outcome and might be used by your doctor to predict the need for further treatment after surgery. Others, such as ER, PgR, and Her2 are associated with a greater likelihood that the cancer may respond to specific types of adjuvant therapy (ie, hormone therapy or antibody therapy) (see below) [3].
Hormone receptors — Some breast cancers have proteins called hormone receptors on their surface; these can be estrogen receptors (ER), progesterone receptors (PgR), or both. If hormone receptors are present in the tumor, women are more likely to benefit from treatments that lower hormone levels or block the actions of these hormones. These treatments are referred to as endocrine or hormone therapies. The test for hormone receptors is usually performed by the pathologist who examines the tumor. (See "Patient information: Adjuvant systemic therapy for hormone-responsive early stage breast cancer in premenopausal women").
Her2 — HER2 is a protein that is present on some breast tumors. Although HER2 is not a very helpful prognostic factor (that is, it does not consistently provide information about whether a tumor is more or less likely to recur), it may help to identify women who are most likely to benefit from specific types of chemotherapy. Furthermore, the presence of HER2 indicates if a woman is likely to benefit from a drug called trastuzumab (Herceptin). (See "Patient information: Adjuvant chemotherapy and trastuzumab (Herceptin) for early stage breast cancer").
Presence of other medical conditions — The presence of other medical conditions may limit the available treatment options for breast cancer.
Personal preferences — Personal preference plays a key role in the treatment of breast cancer. Whenever possible, treatment is individualized to each woman's needs and expectations. Therefore, it is important to meet with a trained medical oncologist to discuss the long term outcomes, benefits of therapy, and risks associated with treatment.
SURGICAL TREATMENT — Surgical removal of the tumor is usually the first step in treating localized breast cancer unless the breast tumor is large or locally invasive. If the cancer is large or locally invasive, another treatment may be recommended before surgery. (See "Patient information: Locally advanced and inflammatory breast cancer", section on "Treatment of locally advanced breast cancer").
There are two options for breast surgery: one involves removing the entire breast (mastectomy) while the other involves removing the tumor and surrounding tissue (lumpectomy). Women who choose lumpectomy usually require additional treatment with radiation to lower the risk of recurrence.
In centers that specialize in breast cancer treatment, approximately 75 percent of women with early stage breast cancer are usually considered appropriate candidates for breast preserving therapy, while the remainder have mastectomy.
MASTECTOMY
Modified radical mastectomy — During a modified radical mastectomy (MRM, show figure 1), the tumor is removed along with all of the breast tissue on the side of the tumor, some of the underlying chest wall tissue, and some of the lymph nodes in the armpit (the axillary lymph nodes). Although the skin of the breast, including the nipple, is removed, the skin covering the chest wall is left intact. The skin is stitched together after removal of the breast. Typically, a draining tube is placed under the skin of the incision for a short time to remove fluid that collects after surgery.
In the United States, modified radical mastectomy is the most common surgery for women with invasive breast cancer.
Total or simple mastectomy — In contrast to MRM, a total or simple mastectomy refers to the removal of the entire breast, not including the arm pit (axillary) lymph nodes. Because the axillary lymph nodes are important for staging and further treatment, total mastectomy has not been considered a standard procedure for women with invasive breast cancer. However, a technique called sentinel node biopsy has allowed total mastectomy to become more popular (see "Sentinel lymph node biopsy" below). Total mastectomy is the treatment of choice for women who are at high risk for a new breast cancer, who therefore decide to have a preventive mastectomy.
Breast reconstruction — Many women choose to have breast reconstruction performed during the same procedure or at a later time. There are several options for reconstruction; frequently, women are evaluated by a plastic or reconstructive surgeon during their initial evaluation to discuss these options prior to the breast surgery.
Complications of mastectomy — Mastectomy is generally a safe surgery, although complications can occur: Collection of fluid (seroma) — Almost all women undergoing mastectomy develop a temporary collection of fluid in the wound, called a seroma. This routine side effect is likely to be more troublesome for women if many lymph nodes must be removed, in obese women, and in women who did not undergo a breast biopsy before the mastectomy. Wound infection — Wound infection occurs in less than 15 percent of women undergoing mastectomy. Infection that occurs soon after mastectomy often appears as an abscess, a collection of pus within the chest wall; infections that occur weeks or months after mastectomy may appear as a cellulitis, an inflammation and infection of the chest wall skin. Arm swelling — Arm swelling (edema) is mostly related to the removal of the axillary lymph nodes, but is also more common in women who undergo mastectomy rather than BCT. Arm edema is more likely to occur in women who undergo removal of the axillary nodes followed by radiation of the armpit area. (See "Patient information: Lymphedema after breast cancer surgery").
Radiation therapy after mastectomy — Radiation therapy of the chest wall after mastectomy may increase the chance of surviving the breast cancer in women who have large tumors (5 cm in size or larger), or who have four or more positive lymph nodes [4]. However, the benefit for women with fewer involved lymph nodes is controversial. The risk of long-term complications of radiation, such as rib fracture or injury to the nerves in the armpit (called the brachial plexus), is less than 5 percent. However, these risks are higher if chemotherapy is given at the same time as radiation or if higher doses of radiation are used.
BREAST CONSERVING THERAPY (BCT) — BCT refers to removal of the part of the breast that contains the tumor, followed by radiation therapy to the remaining breast tissue on the same side.
There are two main types of breast conserving surgery: Lumpectomy — Removal of the tumor and a small amount surrounding breast tissue, show figure 1 Quadrantectomy — Removal of the tumor and about one-fourth of the breast tissue on that side, show figure 1
Lumpectomy is more often used in the United States and Canada, whereas quadrantectomy is more often used in Europe.
Lumpectomy — During lumpectomy, the edges of the removed tissue (called the resection margins) are stained with a special ink and examined under the microscope to check for remaining cancer cells. The surgeon continues to remove additional tissue until no remaining cancer cells are detected by the pathologist (the pathologist examines the tissue while the patient has surgery). During the lumpectomy procedure, lymph nodes in the armpit are usually removed to check for the spread of cancer cells to this area.
Complications of lumpectomy — Lumpectomy is generally a safe surgery, although some complications are possible: Breast cellulitis — Breast cellulitis is an inflammation and infection of the breast tissue. Cellulitis after lumpectomy appears to be related to the presence of bruises after surgery, the collection of fluid in the lymphatic system, and the removal of a large amount of breast tissue. Breast abscess — A breast abscess is a collection of pus within the breast tissue, tends to occur, on average, about five months after BCT. This complication is more common in women following the removal of large amounts of breast tissue.
Radiation therapy
What is radiation therapy? — Radiation therapy (RT) refers to the exposure of a tumor to high-energy x-rays in order to slow or stop its growth. Exposure to x-rays damages cells. Unlike normal cells, cancer cells cannot repair the damage caused by exposure to x-rays, particularly when it is administered over several days. This prevents the cancer cells from growing further and causes them to eventually die.
RT for breast cancer is given as external beam radiation therapy, meaning that the radiation beam is generated by a machine that is outside the patient. The radiation is delivered to the patient, who is usually lying on a table underneath the machine.
Exposure to the beam typically takes only a few seconds (similar to having an x-ray). In general, treatment is repeated five days per week for approximately five to six weeks. Treatment cannot be given over a shorter period because the higher daily doses would cause too many side effects.
Radiation therapy is recommended for the remaining breast tissue on the same side of the tumor after breast conserving surgery. The goal of this radiation therapy is to kill any remaining cancer cells that were not removed during surgery. An extra dose of radiation (called a radiation boost) is often given to the area where the tumor was located.
Benefit of radiation therapy — Studies confirm that radiation plays a critical role in preventing a local recurrence of breast cancer after BCT and in improving survival. In many studies of women undergoing lumpectomy for localized breast cancer, cancer recurred within 20 years in 7 to 14 percent of women who received radiation therapy compared with 26 to 39 percent of women who did not receive this therapy [4-6]. Thus, a local recurrence is approximately three times more likely in women who do not undergo RT. Furthermore, women who receive radiation therapy are also more likely to survive their cancer [4,6].
There is currently no reliable method to identify women who will not have a recurrence if they skip radiation. Therefore, radiation is generally recommended for all women after breast conserving surgery. One possible exception is women over the age of 70 who have small (<2 cm) ER-positive breast cancers; these women are usually initially treated with hormone therapy (eg, tamoxifen) and radiation treatment is not given.
New radiation therapy delivery systems — New ways to give radiotherapy are currently under study. These include short course therapy (giving the treatment over five to ten days instead of four to six weeks), brachytherapy (placing the radiation source directly in the tissues of the breast for a few days), and even intraoperative therapy. Currently, these methods of administering radiation therapy are considered investigational.
Cosmetic results of BCT — With modern surgical techniques, breast conserving therapy has excellent cosmetic results (ie, the treated and untreated breast are almost identical) or good cosmetic results (ie, only slight differences between the treated and untreated breast).
The effects of BCT on the appearance of the breast usually take about three years to stabilize. Factors such as weight gain and the normal age-related sagging of breast tissue may further affect the symmetry of the two breasts.
Several other factors influence the cosmetic results of BCT: Surgical factors — The amount of breast tissue removed during surgery plays a key role in the cosmetic result of BCT. Lumpectomy generally produces a better cosmetic result than quadrantectomy.
Other surgical factors that may affect the cosmetic appearance of the breast after BCT include the size and location of the incision, the postoperative care of the space left by lumpectomy, and the extent of surgery required to remove lymph nodes. Individual factors — Several individual factors also affect the cosmetic result of BCT. These factors include the size of the breast, the size of the tumor, the depth of the tumor within the breast, and the quadrant in which the tumor was located. Use of adjuvant chemotherapy — The use of adjuvant chemotherapy and its timing may affect the cosmetic result of BCT. In one study in women who underwent BCT, the cosmetic results were poorer in women who received radiation therapy and chemotherapy at the same time (concurrent treatment) compared to women receiving chemotherapy followed by radiation therapy (sequential treatment) [7]. This is one of the reasons why chemotherapy is generally given before radiation therapy. (See "Patient information: Adjuvant chemotherapy and trastuzumab (Herceptin) for early stage breast cancer").
Complications following BCT — Following BCT, the following complications may occur: Arm problems — Among women who undergo BCT and axillary lymph node removal, one in five develop arm edema; this is less than the number of women who develop lymphedema after mastectomy [8]. The likelihood of arm swelling is twice as high if the armpit area is radiated after a lymph node dissection. The likelihood of arm edema is also related to the extent of the axillary dissection that is done by the surgeon to evaluate the lymph nodes. (See "Patient information: Lymphedema after breast cancer surgery").
One-half of women may have some temporary loss of shoulder movement, and less than 5 percent of women have damage to the nerves in the armpit (called the brachial plexus) that control arm movement and sensation in the arm. Rib fracture — In less than 5 percent of women who undergo BCT, radiation causes changes in the bones of the chest wall that increase the risk for rib fractures.
MASTECTOMY VERSUS BREAST PRESERVING THERAPY — Numerous studies show that women with localized breast cancer are equally likely to survive their cancer whether they are treated with breast conserving therapy (BCT) or a mastectomy [4,9]. However, it is estimated that fewer than 60 percent of women with early-stage breast cancer are treated with BCT. Some evidence suggests that clinicians encourage women to select mastectomy over BCT, and that women themselves prefer mastectomy to BCT [10]. Furthermore, the selection of BCT is influenced by geographic and socioeconomic factors as well.
Despite the equivalent survival, several factors are taken into consideration when determining whether BCT or mastectomy is a better option for a woman with localized breast cancer.
Medical history and physical examination — A medical history and physical exam are useful to determine a woman's overall health and the presence of other medical conditions. The presence of certain conditions may make BCT or mastectomy a better treatment option. A woman's age alone does not determine if BCT or mastectomy is a better choice.
Results of mammography — A preoperative mammogram is essential for determining the size and extent of the tumor and other tumor features that may affect the choice between BCT or mastectomy.
Microscopic examination of the tumor — Microscopic examination of the tissue removed during a biopsy or during surgery may identify features that affect the recommendation for BCT versus mastectomy. One of these features is the presence of residual cancer cells at the margins. If many residual cancer cells are present after a large amount of tissue has been removed, mastectomy may be preferable.
Individual needs and expectations — Each woman should discuss her expectations and concerns about preserving her breast with her doctor. It is particularly important to consider how the choice of BCT or mastectomy is likely to affect a woman's confidence in the effectiveness of cancer treatment as well as her self-esteem, sexuality, and overall quality of life. The discussion regarding the benefits and risks should include several essential points: The long-term survival after breast cancer The possibility and consequences of a local recurrence The psychological adjustment to treatment (including the fear that cancer will return) The likely cosmetic results Sexuality after treatment
For most women, the likelihood of surviving localized breast cancer is the same with mastectomy or BCT [4,9]; in contrast, the choice of mastectomy versus BCT may have a considerable effect on a woman's quality of life. The overall experience of having breast cancer is equally distressing for women who choose BCT and for those who choose mastectomy. However, compared to women who choose mastectomy, women who choose BCT tend to have a more positive body image and experience fewer changes in their feelings of sexual desirability.
Certain clinical factors clearly favor mastectomy over BCT for medical reasons in individual women. These include: The presence of two or more separate tumors in different areas of the breast Diffuse spread of the tumor in the breast tissue Previous radiation of the breast or chest, which makes future radiation inadvisable Pregnancy in the first or second trimester, which makes radiation inadvisable The presence of many residual cancer cells during breast conserving surgery despite the removal of a large amount of tissue
Certain clinical factors somewhat favor mastectomy over BCT for medical reasons in individual women, although exceptions exist: The presence of certain connective tissue (autoimmune) diseases that are associated with marked side effects from radiation therapy; women with scleroderma and active systemic lupus erythematosus (SLE) are usually advised to select mastectomy over BCT, though women with rheumatoid arthritis can safely undergo radiation therapy and can therefore choose between BCT and mastectomy The presence of several adjacent tumors and the presence of calcium deposits in the same area as the breast tumor A larger tumor size; mastectomy is usually recommended for tumors larger than about two inches and for women who have tumors that are large relative to their breast size The size and shape of the breast; It may be difficult to consistently target radiation in women with very large or pendulous breasts, and these women may be advised to select mastectomy over BCT
Several factors do not play a role in the choice between BCT and mastectomy: The spread of cancer cells to lymph nodes in the armpit The specific location of the tumor within the breast; however, certain tumor locations may reduce the cosmetic results of BCT A family history of breast cancer A high likelihood that cancer will metastasize (recur elsewhere in the body); however, an increased risk of metastases indicates the need for adjuvant therapies
MANAGEMENT OF AXILLARY LYMPH NODES — Although some enlarged lymph nodes can be felt on physical examination, surgery is the only accurate way to determine if the cancer has spread to the lymph nodes in the axilla, or armpit. A complete removal of the axillary lymph nodes, an axillary lymph node dissection (ALND), has traditionally been a routine component of the management of early stage breast cancer for women undergoing both mastectomy and BCT. However, considerable controversy exists regarding whether aggressive treatment of draining nodal areas is indicated. Clearly, the information gained from ALND is prognostic. Furthermore, undertreatment of positive axillary lymph nodes increases the risk of a local recurrence. However, it is unclear if more aggressive treatment of the axillary nodes improves survival. Regardless, more aggressive lymph node treatment (surgery and/or radiation) increases the risk of complications.
The extent of an ALND is determined by the number and location of the nodes removed. The most common complication of ALND is lymphedema, the severity of which depends upon the extent of the ALND. (See "Patient information: Lymphedema after breast cancer surgery"). The desire to accurately identify women who have involved lymph nodes while minimizing the chance of arm swelling has led to the development of the sentinel node biopsy technique.
Sentinel lymph node biopsy — Sentinel node biopsy is an alternative to complete removal of the axillary lymph nodes that has significantly fewer arm complications.
The concept is based on the premise that tumor cells from a breast tumor first involve one or a few lymph nodes before involving lymph nodes in other areas or spreading to distant organs. To identify this sentinel node, the surgeon injects blue dye, a radioactive material, or a combination of both into the area surrounding the tumor, where it enters lymphatic channels and then flows to lymph nodes.
If a SLN is identified, it is removed and examined under the microscope. If this node is does not contain any cancer cells, there is a very small chance that other axillary nodes will be positive and a full ALND is not necessary [11]. In contrast, if the SLN is positive, there is a good chance that other nodes will contain tumor cells, and a full ALND is usually performed.
The main problem with SLN biopsy is that a SLN may be "falsely" negative, meaning that the axillary lymph nodes actually contain tumor cells when the SLN predicts that they do not. The likelihood of a false-negative SLN is related to a surgeon's experience with this procedure. In experienced hands, the risk of a false positive is about 5 percent [12].
Guidelines from the American Society of Clinical Oncology support the use of SLN biopsy as an alternative to full ALND in many patients with early stage breast cancer as long as there is no suspicion from the physical examination that the axillary nodes may be involved with tumor spread [11].
RECURRENCE AFTER BCT — A local recurrence refers to a return of cancer in the breast tissue or the surrounding chest wall. After mastectomy, local recurrences are in the chest wall because there is no remaining breast tissue; following BCT, a recurrence is usually within the remaining breast tissue.
In women with stage I or II breast cancer, local recurrence develops in 7 to 20 percent of women treated with BCT, and in 4 to 14 percent of women treated with mastectomy. However, the time course of recurrence is different. A local recurrence is often delayed for many years in women treated with BCT, whereas a local recurrence usually occurs within three years in women treated with mastectomy.
It is important to note that BCT does not completely prevent new breast cancers from arising in the remaining breast tissue. In women treated with BCT, the risk of a new, unrelated tumor on the same side is about 1 percent per year (eg, 13 percent risk over 15 years following the procedure).
Surveillance — Women who have undergone BCT must continue to perform breast self-exams and undergo screening of both breasts with mammography. A summary of the American Society of Clinical Oncology's recommendations for surveillance after breast cancer treatment is provided in table 2 (show table 2).
Risk factors — The likelihood that breast cancer will recur locally after BCT is influenced by individual factors, tumor factors, and treatment factors.
Individual factors — A woman's age appears to influence the risk of a local recurrence after BCT. Women who are age 40 years or younger at the time of BCT are more likely than older women to have a local recurrence after BCT. Other studies suggest that younger women may also be more likely to have a local recurrence after mastectomy. Thus, young age should not be used as a factor in choosing one treatment over another, but instead should be used as an indicator of a higher risk of a local recurrence.
Tumor factors — The likelihood of a local recurrence after BCT is also influenced by two tumor-related factors: Residual cancer cells at the edge of the wound — The presence of residual cancer cells at the edge of the wound (called the resection margin) increases the likelihood of a local recurrence after BCT. In one study, the rate of local recurrence after BCT was 7 percent in women in whom no residual cells are found, compared to 18 percent in women in whom residual cancer cells were found [13]. Although the surgeon will try to remove all of these cells during surgery, residual cells are sometimes detected after surgery on more detailed microscopic examination. Presence of cancer cells within ducts — The presence of cancer cells within many ducts of the removed breast tissue, termed an extensive intraductal component, is useful for assessing the likelihood of a local recurrence. A local recurrence is more likely when cancer cells are present in many ducts within the tumor or within the normal breast tissue, if tumor cells remain at the margin of resection. Certain findings on mammograms taken before surgery often alert the surgeon to the presence of cancer cells in ducts. In such cases, particular care must be taken by the surgeon to make certain that no remaining tumor cells are present at the surgical margins.
Treatment factors — Three treatment factors influence the likelihood of a local recurrence after BCT: Extent of surgery — Local recurrence of breast cancer after BCT is less likely when a greater amount of breast tissue is removed during surgery. Radiation boost — A radiation boost refers to the delivery of an extra dose of radiation to the area of the breast where the tumor was located. Some, but not all studies suggest that a radiation boost slightly reduces the likelihood of a local recurrence of breast cancer, although this boost may slightly reduce the cosmetic results of BCT. Chemotherapy or hormone therapy — Chemotherapy and/or hormonal therapy are often recommended following surgery for localized breast cancer. The addition of these therapies to BCT further reduces the likelihood of a local recurrence, although not all women will need both of these therapies.
As an example, in one study of women with node-negative, ER-negative breast cancer, women were treated with chemotherapy or no chemotherapy after BCT [14]. Cancer recurred locally within eight years in 2.6 percent of the women treated with chemotherapy and in 13.4 percent of the women who were not treated with chemotherapy.
In a second study in women with node-negative, ER-positive breast cancer, women were treated with tamoxifen or a placebo after BCT [15]. Cancer recurred locally within ten years in 4.3 percent of the women treated with tamoxifen, and in 14.7 percent of the women who were treated a placebo.
Treatment — Many women who have a local recurrence can undergo a "salvage" mastectomy, and still have a chance to be cured from their cancer if there is no further spread.
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Cancer Institute
1-800-4-CANCER
(www.nci.nih.gov)
People Living With Cancer: The official patient information
website of the American Society of Clinical Oncology
(www.plwc.org/portal/site/PLWC)
National Comprehensive Cancer Network
(www.nccn.org/patients/patient_gls.asp)
American Cancer Society
1-800-ACS-2345
(www.cancer.org)
National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
Susan G. Komen Breast Cancer Foundation
(www.komen.org)
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Saslow, D, Boetes, C, Burke, W, et al. American Cancer Society guidelines for breast cancer screening with MRI as an adjunct to mammography. CA Cancer J Clin 2007; 57:75.
2. Lehman, CD, Gatsonis, C, Kuhl, CK, et al. MRI evaluation of the contralateral breast in women with recently diagnosed breast cancer. N Engl J Med 2007; 356:1295.
3. Yamauchi, H, Stearns, V, Hayes, DF. When is a tumor marker ready for prime time? A case study of c-erbB-2 as a predictive factor in breast cancer. J Clin Oncol 2001; 19:2334.
4. Clarke, M, Collins, R, Darby, S, et al. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005; 366:2087.
5. Fisher, B, Anderson, S, Bryant, J, et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med 2002; 347:1233.
6. Vinh-Hung, V, Verschraegen, C. Breast-conserving surgery with or without radiotherapy: pooled-analysis for risks of ipsilateral breast tumor recurrence and mortality. J Natl Cancer Inst 2004; 96:115.
7. Abner, AL, Recht, A, Vicini, FA, et al. Cosmetic results after surgery, chemotherapy, and radiation therapy for early breast cancer. Int J Radiat Oncol Biol Phys 1991; 21:331.
8. Erickson, VS, Pearson, ML, Ganz, PA, et al. Arm edema in breast cancer patients. J Natl Cancer Inst 2001; 93:96.
9. NIH Consensus Development Conference statement on the treatment of early-stage breast cancer. Oncology (Huntingt) 1991; 5:120.
10. Morrow, M, White, J, Moughan, J, et al. Factors predicting the use of breast-conserving therapy in stage I and II breast carcinoma. J Clin Oncol 2001; 19:2254.
11. Lyman, GH, Giuliano, AE, Somerfield, MR, et al. American Society of Clinical Oncology Guideline Recommendations for Sentinel Lymph Node Biopsy in Early-Stage Breast Cancer. J Clin Oncol 2005; 23:7703.
12. Guidelines from the American Society of Breast Surgeons available online at www.breastsurgeons.org/officialstmts/sentinel.shtml (accessed September 13, 2005).
13. Park, CC, Mitsumori, M, Nixon, A, et al. Outcome at 8 years after breast-conserving surgery and radiation therapy for invasive breast cancer: influence of margin status and systemic therapy on local recurrence. J Clin Oncol 2000; 18:1668.
14. Fisher, B, Dignam, J, Mamounas, EP, et al. Sequential methotrexate and fluorouracil for the treatment of node-negative breast cancer patients with estrogen receptor-negative tumors: eight-year results from National Surgical Adjuvant Breast and Bowel Project (NSABP) B-13 and first report of findings from NSABP B-19 comparing methotrexate and fluorouracil with conventional cyclophosphamide, methotrexate, and fluorouracil. J Clin Oncol 1996; 14:1982.
15. Fisher, B, Dignam, J, Bryant, J, et al. Five versus more than five years of tamoxifen therapy for breast cancer patients with negative lymph nodes and estrogen receptor-positive tumors. J Natl Cancer Inst 1996; 88:1529.
Two surgical options are available for treating localized breast cancer: mastectomy (removal of the breast) and breast preserving therapy. After either surgery, systemic (bodywide) therapy is often recommended to decrease the likelihood that the cancer will return. The options for systemic therapy include chemotherapy, hormone therapy, or antibody therapy. (See "Patient information: Adjuvant chemotherapy and trastuzumab (Herceptin) for early stage breast cancer").
The treatment of localized breast cancer must be individualized and is based upon several factors. Optimal management requires collaboration between surgeons and physicians who specialize in radiation and medical oncology. Each woman should carefully discuss the available treatment options with her doctors to determine which is the best choice for her.
BREAST CANCER STAGING — Treatment and prognosis (outcome) depend upon the stage of the cancer, which is based upon the size of the tumor, involvement of the skin, chest wall or local lymph nodes, and whether the cancer has spread to other organs (called metastasis). In situ carcinomas (eg, ductal carcinoma in situ, lobular carcinoma in situ) are the earliest recognizable breast cancers and rarely spread beyond the breast tissue; more advanced breast cancers, which are referred to as invasive carcinomas, metastasize more often.
The size of the breast tumor, involvement of adjacent lymph nodes, and the presence or absence of spread to other organs are described by the "stage grouping" of a breast cancer, which ranges from stage I to IV. Table 1 summarizes these stages (show table 1). Localized invasive breast cancer generally refers to stage I to IIIA breast cancer. (See "TNM staging classification for breast cancer").
The initial evaluation to determine the stage of a breast cancer usually involves a physical examination, mammogram, chest X-ray, and sometimes CT scans (specialized x-rays) and/or a bone scan. An important component of the staging work-up is an evaluation of the opposite breast. Breast MRI may be recommended to screen the opposite breast for cancer in women who have a breast cancer on one side and who have no abnormalities noted within the opposite breast by either physical examination or mammogram [1,2].
The final stage of the cancer depends upon what is found during microscopic examination of the breast and lymph node tissue after surgery; this is called the pathologic stage, and it is the most accurate indicator of tumor extent and prognosis.
FACTORS AFFECTING TREATMENT — Several factors must be considered when choosing the best treatment for localized breast cancer.
Microscopic findings — There are many different varieties of breast cancer as viewed by the pathologist under the microscope. However, from the standpoint of treatment, the most important distinction is between invasive and noninvasive (in situ) breast cancer. Localized invasive breast cancers are generally approached similarly, whether they are ductal, lobular, or any of the so-called "special types" (tubular, mucinous, colloid, medullary). The surgical treatment of in situ cancers is similar to that of invasive cancers, but postoperative adjuvant systemic therapy is generally not recommended.
Size of the breast tumor — The prognosis of a breast cancer depends upon its size; larger tumors recur more often, and usually require more aggressive treatment. In some cases, chemotherapy may be given before surgery to shrink a large tumor or one that has grown into the chest wall. Inflammatory breast cancer refers to any breast cancer that is associated with an "inflamed" appearance of the breast (show picture 1 and show picture 2); this implies spread of the tumor into the lymph system of the overlying skin. These cancers are treated similarly to large tumors, with chemotherapy preceding surgery or radiation. (See "Patient information: Locally advanced and inflammatory breast cancer").
Spread of cancer cells to the lymph nodes — Fluid from the breast tissue normally drains into lymph nodes located in the armpit (the axilla). These nodes (or glands) are often the first site of spread for breast cancer. If a breast cancer has spread to lymph nodes, it is called node-positive; a cancer that has not spread to the lymph nodes is called node-negative. This is an important distinction because if a breast cancer has spread to the lymph nodes, it is twice as likely to have spread elsewhere, and therefore, to recur over the succeeding years postoperatively.
Most women with node-positive breast cancer should receive adjuvant chemotherapy or hormone therapy after surgery, even if the tumor was completely removed. (See "Patient information: Adjuvant chemotherapy and trastuzumab (Herceptin) for early stage breast cancer").
Tumor markers and prognostic factors — Studies suggest that certain markers or characteristics of the tumor may help determine the prognosis or outcome of breast cancer. Some of these tests are hormone receptors, S phase analysis (a measure of cell proliferation or growth), Her2 status. Levels of plasminogen activators (called uPA and PAI-1) are also measured in certain countries, but not routinely in the United States. All of these tests are performed on the tumor material by the pathologist.
Some of these factors may be associated with a worse outcome and might be used by your doctor to predict the need for further treatment after surgery. Others, such as ER, PgR, and Her2 are associated with a greater likelihood that the cancer may respond to specific types of adjuvant therapy (ie, hormone therapy or antibody therapy) (see below) [3].
Hormone receptors — Some breast cancers have proteins called hormone receptors on their surface; these can be estrogen receptors (ER), progesterone receptors (PgR), or both. If hormone receptors are present in the tumor, women are more likely to benefit from treatments that lower hormone levels or block the actions of these hormones. These treatments are referred to as endocrine or hormone therapies. The test for hormone receptors is usually performed by the pathologist who examines the tumor. (See "Patient information: Adjuvant systemic therapy for hormone-responsive early stage breast cancer in premenopausal women").
Her2 — HER2 is a protein that is present on some breast tumors. Although HER2 is not a very helpful prognostic factor (that is, it does not consistently provide information about whether a tumor is more or less likely to recur), it may help to identify women who are most likely to benefit from specific types of chemotherapy. Furthermore, the presence of HER2 indicates if a woman is likely to benefit from a drug called trastuzumab (Herceptin). (See "Patient information: Adjuvant chemotherapy and trastuzumab (Herceptin) for early stage breast cancer").
Presence of other medical conditions — The presence of other medical conditions may limit the available treatment options for breast cancer.
Personal preferences — Personal preference plays a key role in the treatment of breast cancer. Whenever possible, treatment is individualized to each woman's needs and expectations. Therefore, it is important to meet with a trained medical oncologist to discuss the long term outcomes, benefits of therapy, and risks associated with treatment.
SURGICAL TREATMENT — Surgical removal of the tumor is usually the first step in treating localized breast cancer unless the breast tumor is large or locally invasive. If the cancer is large or locally invasive, another treatment may be recommended before surgery. (See "Patient information: Locally advanced and inflammatory breast cancer", section on "Treatment of locally advanced breast cancer").
There are two options for breast surgery: one involves removing the entire breast (mastectomy) while the other involves removing the tumor and surrounding tissue (lumpectomy). Women who choose lumpectomy usually require additional treatment with radiation to lower the risk of recurrence.
In centers that specialize in breast cancer treatment, approximately 75 percent of women with early stage breast cancer are usually considered appropriate candidates for breast preserving therapy, while the remainder have mastectomy.
MASTECTOMY
Modified radical mastectomy — During a modified radical mastectomy (MRM, show figure 1), the tumor is removed along with all of the breast tissue on the side of the tumor, some of the underlying chest wall tissue, and some of the lymph nodes in the armpit (the axillary lymph nodes). Although the skin of the breast, including the nipple, is removed, the skin covering the chest wall is left intact. The skin is stitched together after removal of the breast. Typically, a draining tube is placed under the skin of the incision for a short time to remove fluid that collects after surgery.
In the United States, modified radical mastectomy is the most common surgery for women with invasive breast cancer.
Total or simple mastectomy — In contrast to MRM, a total or simple mastectomy refers to the removal of the entire breast, not including the arm pit (axillary) lymph nodes. Because the axillary lymph nodes are important for staging and further treatment, total mastectomy has not been considered a standard procedure for women with invasive breast cancer. However, a technique called sentinel node biopsy has allowed total mastectomy to become more popular (see "Sentinel lymph node biopsy" below). Total mastectomy is the treatment of choice for women who are at high risk for a new breast cancer, who therefore decide to have a preventive mastectomy.
Breast reconstruction — Many women choose to have breast reconstruction performed during the same procedure or at a later time. There are several options for reconstruction; frequently, women are evaluated by a plastic or reconstructive surgeon during their initial evaluation to discuss these options prior to the breast surgery.
Complications of mastectomy — Mastectomy is generally a safe surgery, although complications can occur: Collection of fluid (seroma) — Almost all women undergoing mastectomy develop a temporary collection of fluid in the wound, called a seroma. This routine side effect is likely to be more troublesome for women if many lymph nodes must be removed, in obese women, and in women who did not undergo a breast biopsy before the mastectomy. Wound infection — Wound infection occurs in less than 15 percent of women undergoing mastectomy. Infection that occurs soon after mastectomy often appears as an abscess, a collection of pus within the chest wall; infections that occur weeks or months after mastectomy may appear as a cellulitis, an inflammation and infection of the chest wall skin. Arm swelling — Arm swelling (edema) is mostly related to the removal of the axillary lymph nodes, but is also more common in women who undergo mastectomy rather than BCT. Arm edema is more likely to occur in women who undergo removal of the axillary nodes followed by radiation of the armpit area. (See "Patient information: Lymphedema after breast cancer surgery").
Radiation therapy after mastectomy — Radiation therapy of the chest wall after mastectomy may increase the chance of surviving the breast cancer in women who have large tumors (5 cm in size or larger), or who have four or more positive lymph nodes [4]. However, the benefit for women with fewer involved lymph nodes is controversial. The risk of long-term complications of radiation, such as rib fracture or injury to the nerves in the armpit (called the brachial plexus), is less than 5 percent. However, these risks are higher if chemotherapy is given at the same time as radiation or if higher doses of radiation are used.
BREAST CONSERVING THERAPY (BCT) — BCT refers to removal of the part of the breast that contains the tumor, followed by radiation therapy to the remaining breast tissue on the same side.
There are two main types of breast conserving surgery: Lumpectomy — Removal of the tumor and a small amount surrounding breast tissue, show figure 1 Quadrantectomy — Removal of the tumor and about one-fourth of the breast tissue on that side, show figure 1
Lumpectomy is more often used in the United States and Canada, whereas quadrantectomy is more often used in Europe.
Lumpectomy — During lumpectomy, the edges of the removed tissue (called the resection margins) are stained with a special ink and examined under the microscope to check for remaining cancer cells. The surgeon continues to remove additional tissue until no remaining cancer cells are detected by the pathologist (the pathologist examines the tissue while the patient has surgery). During the lumpectomy procedure, lymph nodes in the armpit are usually removed to check for the spread of cancer cells to this area.
Complications of lumpectomy — Lumpectomy is generally a safe surgery, although some complications are possible: Breast cellulitis — Breast cellulitis is an inflammation and infection of the breast tissue. Cellulitis after lumpectomy appears to be related to the presence of bruises after surgery, the collection of fluid in the lymphatic system, and the removal of a large amount of breast tissue. Breast abscess — A breast abscess is a collection of pus within the breast tissue, tends to occur, on average, about five months after BCT. This complication is more common in women following the removal of large amounts of breast tissue.
Radiation therapy
What is radiation therapy? — Radiation therapy (RT) refers to the exposure of a tumor to high-energy x-rays in order to slow or stop its growth. Exposure to x-rays damages cells. Unlike normal cells, cancer cells cannot repair the damage caused by exposure to x-rays, particularly when it is administered over several days. This prevents the cancer cells from growing further and causes them to eventually die.
RT for breast cancer is given as external beam radiation therapy, meaning that the radiation beam is generated by a machine that is outside the patient. The radiation is delivered to the patient, who is usually lying on a table underneath the machine.
Exposure to the beam typically takes only a few seconds (similar to having an x-ray). In general, treatment is repeated five days per week for approximately five to six weeks. Treatment cannot be given over a shorter period because the higher daily doses would cause too many side effects.
Radiation therapy is recommended for the remaining breast tissue on the same side of the tumor after breast conserving surgery. The goal of this radiation therapy is to kill any remaining cancer cells that were not removed during surgery. An extra dose of radiation (called a radiation boost) is often given to the area where the tumor was located.
Benefit of radiation therapy — Studies confirm that radiation plays a critical role in preventing a local recurrence of breast cancer after BCT and in improving survival. In many studies of women undergoing lumpectomy for localized breast cancer, cancer recurred within 20 years in 7 to 14 percent of women who received radiation therapy compared with 26 to 39 percent of women who did not receive this therapy [4-6]. Thus, a local recurrence is approximately three times more likely in women who do not undergo RT. Furthermore, women who receive radiation therapy are also more likely to survive their cancer [4,6].
There is currently no reliable method to identify women who will not have a recurrence if they skip radiation. Therefore, radiation is generally recommended for all women after breast conserving surgery. One possible exception is women over the age of 70 who have small (<2 cm) ER-positive breast cancers; these women are usually initially treated with hormone therapy (eg, tamoxifen) and radiation treatment is not given.
New radiation therapy delivery systems — New ways to give radiotherapy are currently under study. These include short course therapy (giving the treatment over five to ten days instead of four to six weeks), brachytherapy (placing the radiation source directly in the tissues of the breast for a few days), and even intraoperative therapy. Currently, these methods of administering radiation therapy are considered investigational.
Cosmetic results of BCT — With modern surgical techniques, breast conserving therapy has excellent cosmetic results (ie, the treated and untreated breast are almost identical) or good cosmetic results (ie, only slight differences between the treated and untreated breast).
The effects of BCT on the appearance of the breast usually take about three years to stabilize. Factors such as weight gain and the normal age-related sagging of breast tissue may further affect the symmetry of the two breasts.
Several other factors influence the cosmetic results of BCT: Surgical factors — The amount of breast tissue removed during surgery plays a key role in the cosmetic result of BCT. Lumpectomy generally produces a better cosmetic result than quadrantectomy.
Other surgical factors that may affect the cosmetic appearance of the breast after BCT include the size and location of the incision, the postoperative care of the space left by lumpectomy, and the extent of surgery required to remove lymph nodes. Individual factors — Several individual factors also affect the cosmetic result of BCT. These factors include the size of the breast, the size of the tumor, the depth of the tumor within the breast, and the quadrant in which the tumor was located. Use of adjuvant chemotherapy — The use of adjuvant chemotherapy and its timing may affect the cosmetic result of BCT. In one study in women who underwent BCT, the cosmetic results were poorer in women who received radiation therapy and chemotherapy at the same time (concurrent treatment) compared to women receiving chemotherapy followed by radiation therapy (sequential treatment) [7]. This is one of the reasons why chemotherapy is generally given before radiation therapy. (See "Patient information: Adjuvant chemotherapy and trastuzumab (Herceptin) for early stage breast cancer").
Complications following BCT — Following BCT, the following complications may occur: Arm problems — Among women who undergo BCT and axillary lymph node removal, one in five develop arm edema; this is less than the number of women who develop lymphedema after mastectomy [8]. The likelihood of arm swelling is twice as high if the armpit area is radiated after a lymph node dissection. The likelihood of arm edema is also related to the extent of the axillary dissection that is done by the surgeon to evaluate the lymph nodes. (See "Patient information: Lymphedema after breast cancer surgery").
One-half of women may have some temporary loss of shoulder movement, and less than 5 percent of women have damage to the nerves in the armpit (called the brachial plexus) that control arm movement and sensation in the arm. Rib fracture — In less than 5 percent of women who undergo BCT, radiation causes changes in the bones of the chest wall that increase the risk for rib fractures.
MASTECTOMY VERSUS BREAST PRESERVING THERAPY — Numerous studies show that women with localized breast cancer are equally likely to survive their cancer whether they are treated with breast conserving therapy (BCT) or a mastectomy [4,9]. However, it is estimated that fewer than 60 percent of women with early-stage breast cancer are treated with BCT. Some evidence suggests that clinicians encourage women to select mastectomy over BCT, and that women themselves prefer mastectomy to BCT [10]. Furthermore, the selection of BCT is influenced by geographic and socioeconomic factors as well.
Despite the equivalent survival, several factors are taken into consideration when determining whether BCT or mastectomy is a better option for a woman with localized breast cancer.
Medical history and physical examination — A medical history and physical exam are useful to determine a woman's overall health and the presence of other medical conditions. The presence of certain conditions may make BCT or mastectomy a better treatment option. A woman's age alone does not determine if BCT or mastectomy is a better choice.
Results of mammography — A preoperative mammogram is essential for determining the size and extent of the tumor and other tumor features that may affect the choice between BCT or mastectomy.
Microscopic examination of the tumor — Microscopic examination of the tissue removed during a biopsy or during surgery may identify features that affect the recommendation for BCT versus mastectomy. One of these features is the presence of residual cancer cells at the margins. If many residual cancer cells are present after a large amount of tissue has been removed, mastectomy may be preferable.
Individual needs and expectations — Each woman should discuss her expectations and concerns about preserving her breast with her doctor. It is particularly important to consider how the choice of BCT or mastectomy is likely to affect a woman's confidence in the effectiveness of cancer treatment as well as her self-esteem, sexuality, and overall quality of life. The discussion regarding the benefits and risks should include several essential points: The long-term survival after breast cancer The possibility and consequences of a local recurrence The psychological adjustment to treatment (including the fear that cancer will return) The likely cosmetic results Sexuality after treatment
For most women, the likelihood of surviving localized breast cancer is the same with mastectomy or BCT [4,9]; in contrast, the choice of mastectomy versus BCT may have a considerable effect on a woman's quality of life. The overall experience of having breast cancer is equally distressing for women who choose BCT and for those who choose mastectomy. However, compared to women who choose mastectomy, women who choose BCT tend to have a more positive body image and experience fewer changes in their feelings of sexual desirability.
Certain clinical factors clearly favor mastectomy over BCT for medical reasons in individual women. These include: The presence of two or more separate tumors in different areas of the breast Diffuse spread of the tumor in the breast tissue Previous radiation of the breast or chest, which makes future radiation inadvisable Pregnancy in the first or second trimester, which makes radiation inadvisable The presence of many residual cancer cells during breast conserving surgery despite the removal of a large amount of tissue
Certain clinical factors somewhat favor mastectomy over BCT for medical reasons in individual women, although exceptions exist: The presence of certain connective tissue (autoimmune) diseases that are associated with marked side effects from radiation therapy; women with scleroderma and active systemic lupus erythematosus (SLE) are usually advised to select mastectomy over BCT, though women with rheumatoid arthritis can safely undergo radiation therapy and can therefore choose between BCT and mastectomy The presence of several adjacent tumors and the presence of calcium deposits in the same area as the breast tumor A larger tumor size; mastectomy is usually recommended for tumors larger than about two inches and for women who have tumors that are large relative to their breast size The size and shape of the breast; It may be difficult to consistently target radiation in women with very large or pendulous breasts, and these women may be advised to select mastectomy over BCT
Several factors do not play a role in the choice between BCT and mastectomy: The spread of cancer cells to lymph nodes in the armpit The specific location of the tumor within the breast; however, certain tumor locations may reduce the cosmetic results of BCT A family history of breast cancer A high likelihood that cancer will metastasize (recur elsewhere in the body); however, an increased risk of metastases indicates the need for adjuvant therapies
MANAGEMENT OF AXILLARY LYMPH NODES — Although some enlarged lymph nodes can be felt on physical examination, surgery is the only accurate way to determine if the cancer has spread to the lymph nodes in the axilla, or armpit. A complete removal of the axillary lymph nodes, an axillary lymph node dissection (ALND), has traditionally been a routine component of the management of early stage breast cancer for women undergoing both mastectomy and BCT. However, considerable controversy exists regarding whether aggressive treatment of draining nodal areas is indicated. Clearly, the information gained from ALND is prognostic. Furthermore, undertreatment of positive axillary lymph nodes increases the risk of a local recurrence. However, it is unclear if more aggressive treatment of the axillary nodes improves survival. Regardless, more aggressive lymph node treatment (surgery and/or radiation) increases the risk of complications.
The extent of an ALND is determined by the number and location of the nodes removed. The most common complication of ALND is lymphedema, the severity of which depends upon the extent of the ALND. (See "Patient information: Lymphedema after breast cancer surgery"). The desire to accurately identify women who have involved lymph nodes while minimizing the chance of arm swelling has led to the development of the sentinel node biopsy technique.
Sentinel lymph node biopsy — Sentinel node biopsy is an alternative to complete removal of the axillary lymph nodes that has significantly fewer arm complications.
The concept is based on the premise that tumor cells from a breast tumor first involve one or a few lymph nodes before involving lymph nodes in other areas or spreading to distant organs. To identify this sentinel node, the surgeon injects blue dye, a radioactive material, or a combination of both into the area surrounding the tumor, where it enters lymphatic channels and then flows to lymph nodes.
If a SLN is identified, it is removed and examined under the microscope. If this node is does not contain any cancer cells, there is a very small chance that other axillary nodes will be positive and a full ALND is not necessary [11]. In contrast, if the SLN is positive, there is a good chance that other nodes will contain tumor cells, and a full ALND is usually performed.
The main problem with SLN biopsy is that a SLN may be "falsely" negative, meaning that the axillary lymph nodes actually contain tumor cells when the SLN predicts that they do not. The likelihood of a false-negative SLN is related to a surgeon's experience with this procedure. In experienced hands, the risk of a false positive is about 5 percent [12].
Guidelines from the American Society of Clinical Oncology support the use of SLN biopsy as an alternative to full ALND in many patients with early stage breast cancer as long as there is no suspicion from the physical examination that the axillary nodes may be involved with tumor spread [11].
RECURRENCE AFTER BCT — A local recurrence refers to a return of cancer in the breast tissue or the surrounding chest wall. After mastectomy, local recurrences are in the chest wall because there is no remaining breast tissue; following BCT, a recurrence is usually within the remaining breast tissue.
In women with stage I or II breast cancer, local recurrence develops in 7 to 20 percent of women treated with BCT, and in 4 to 14 percent of women treated with mastectomy. However, the time course of recurrence is different. A local recurrence is often delayed for many years in women treated with BCT, whereas a local recurrence usually occurs within three years in women treated with mastectomy.
It is important to note that BCT does not completely prevent new breast cancers from arising in the remaining breast tissue. In women treated with BCT, the risk of a new, unrelated tumor on the same side is about 1 percent per year (eg, 13 percent risk over 15 years following the procedure).
Surveillance — Women who have undergone BCT must continue to perform breast self-exams and undergo screening of both breasts with mammography. A summary of the American Society of Clinical Oncology's recommendations for surveillance after breast cancer treatment is provided in table 2 (show table 2).
Risk factors — The likelihood that breast cancer will recur locally after BCT is influenced by individual factors, tumor factors, and treatment factors.
Individual factors — A woman's age appears to influence the risk of a local recurrence after BCT. Women who are age 40 years or younger at the time of BCT are more likely than older women to have a local recurrence after BCT. Other studies suggest that younger women may also be more likely to have a local recurrence after mastectomy. Thus, young age should not be used as a factor in choosing one treatment over another, but instead should be used as an indicator of a higher risk of a local recurrence.
Tumor factors — The likelihood of a local recurrence after BCT is also influenced by two tumor-related factors: Residual cancer cells at the edge of the wound — The presence of residual cancer cells at the edge of the wound (called the resection margin) increases the likelihood of a local recurrence after BCT. In one study, the rate of local recurrence after BCT was 7 percent in women in whom no residual cells are found, compared to 18 percent in women in whom residual cancer cells were found [13]. Although the surgeon will try to remove all of these cells during surgery, residual cells are sometimes detected after surgery on more detailed microscopic examination. Presence of cancer cells within ducts — The presence of cancer cells within many ducts of the removed breast tissue, termed an extensive intraductal component, is useful for assessing the likelihood of a local recurrence. A local recurrence is more likely when cancer cells are present in many ducts within the tumor or within the normal breast tissue, if tumor cells remain at the margin of resection. Certain findings on mammograms taken before surgery often alert the surgeon to the presence of cancer cells in ducts. In such cases, particular care must be taken by the surgeon to make certain that no remaining tumor cells are present at the surgical margins.
Treatment factors — Three treatment factors influence the likelihood of a local recurrence after BCT: Extent of surgery — Local recurrence of breast cancer after BCT is less likely when a greater amount of breast tissue is removed during surgery. Radiation boost — A radiation boost refers to the delivery of an extra dose of radiation to the area of the breast where the tumor was located. Some, but not all studies suggest that a radiation boost slightly reduces the likelihood of a local recurrence of breast cancer, although this boost may slightly reduce the cosmetic results of BCT. Chemotherapy or hormone therapy — Chemotherapy and/or hormonal therapy are often recommended following surgery for localized breast cancer. The addition of these therapies to BCT further reduces the likelihood of a local recurrence, although not all women will need both of these therapies.
As an example, in one study of women with node-negative, ER-negative breast cancer, women were treated with chemotherapy or no chemotherapy after BCT [14]. Cancer recurred locally within eight years in 2.6 percent of the women treated with chemotherapy and in 13.4 percent of the women who were not treated with chemotherapy.
In a second study in women with node-negative, ER-positive breast cancer, women were treated with tamoxifen or a placebo after BCT [15]. Cancer recurred locally within ten years in 4.3 percent of the women treated with tamoxifen, and in 14.7 percent of the women who were treated a placebo.
Treatment — Many women who have a local recurrence can undergo a "salvage" mastectomy, and still have a chance to be cured from their cancer if there is no further spread.
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Cancer Institute
1-800-4-CANCER
(www.nci.nih.gov)
People Living With Cancer: The official patient information
website of the American Society of Clinical Oncology
(www.plwc.org/portal/site/PLWC)
National Comprehensive Cancer Network
(www.nccn.org/patients/patient_gls.asp)
American Cancer Society
1-800-ACS-2345
(www.cancer.org)
National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
Susan G. Komen Breast Cancer Foundation
(www.komen.org)
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Saslow, D, Boetes, C, Burke, W, et al. American Cancer Society guidelines for breast cancer screening with MRI as an adjunct to mammography. CA Cancer J Clin 2007; 57:75.
2. Lehman, CD, Gatsonis, C, Kuhl, CK, et al. MRI evaluation of the contralateral breast in women with recently diagnosed breast cancer. N Engl J Med 2007; 356:1295.
3. Yamauchi, H, Stearns, V, Hayes, DF. When is a tumor marker ready for prime time? A case study of c-erbB-2 as a predictive factor in breast cancer. J Clin Oncol 2001; 19:2334.
4. Clarke, M, Collins, R, Darby, S, et al. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005; 366:2087.
5. Fisher, B, Anderson, S, Bryant, J, et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med 2002; 347:1233.
6. Vinh-Hung, V, Verschraegen, C. Breast-conserving surgery with or without radiotherapy: pooled-analysis for risks of ipsilateral breast tumor recurrence and mortality. J Natl Cancer Inst 2004; 96:115.
7. Abner, AL, Recht, A, Vicini, FA, et al. Cosmetic results after surgery, chemotherapy, and radiation therapy for early breast cancer. Int J Radiat Oncol Biol Phys 1991; 21:331.
8. Erickson, VS, Pearson, ML, Ganz, PA, et al. Arm edema in breast cancer patients. J Natl Cancer Inst 2001; 93:96.
9. NIH Consensus Development Conference statement on the treatment of early-stage breast cancer. Oncology (Huntingt) 1991; 5:120.
10. Morrow, M, White, J, Moughan, J, et al. Factors predicting the use of breast-conserving therapy in stage I and II breast carcinoma. J Clin Oncol 2001; 19:2254.
11. Lyman, GH, Giuliano, AE, Somerfield, MR, et al. American Society of Clinical Oncology Guideline Recommendations for Sentinel Lymph Node Biopsy in Early-Stage Breast Cancer. J Clin Oncol 2005; 23:7703.
12. Guidelines from the American Society of Breast Surgeons available online at www.breastsurgeons.org/officialstmts/sentinel.shtml (accessed September 13, 2005).
13. Park, CC, Mitsumori, M, Nixon, A, et al. Outcome at 8 years after breast-conserving surgery and radiation therapy for invasive breast cancer: influence of margin status and systemic therapy on local recurrence. J Clin Oncol 2000; 18:1668.
14. Fisher, B, Dignam, J, Mamounas, EP, et al. Sequential methotrexate and fluorouracil for the treatment of node-negative breast cancer patients with estrogen receptor-negative tumors: eight-year results from National Surgical Adjuvant Breast and Bowel Project (NSABP) B-13 and first report of findings from NSABP B-19 comparing methotrexate and fluorouracil with conventional cyclophosphamide, methotrexate, and fluorouracil. J Clin Oncol 1996; 14:1982.
15. Fisher, B, Dignam, J, Bryant, J, et al. Five versus more than five years of tamoxifen therapy for breast cancer patients with negative lymph nodes and estrogen receptor-positive tumors. J Natl Cancer Inst 1996; 88:1529.
Localized breast cancer evaluation, mastectomy, and breast conserving therapy
INTRODUCTION — Breast cancer is the most common female cancer in the United States, the second most common cause of cancer death in women (after lung cancer), and the main cause of death in women ages 45 to 55. Every year, approximately 180,000 American women will be diagnosed with breast cancer, and more than 40,000 will die from it. Early detection and treatment of breast cancer clearly improves survival, by removing the breast tumor before it has a chance to spread (metastasize).
Two surgical options are available for treating localized breast cancer: mastectomy (removal of the breast) and breast preserving therapy. After either surgery, systemic (bodywide) therapy is often recommended to decrease the likelihood that the cancer will return. The options for systemic therapy include chemotherapy, hormone therapy, or antibody therapy. (See "Patient information: Adjuvant chemotherapy and trastuzumab (Herceptin) for early stage breast cancer").
The treatment of localized breast cancer must be individualized and is based upon several factors. Optimal management requires collaboration between surgeons and physicians who specialize in radiation and medical oncology. Each woman should carefully discuss the available treatment options with her doctors to determine which is the best choice for her.
BREAST CANCER STAGING — Treatment and prognosis (outcome) depend upon the stage of the cancer, which is based upon the size of the tumor, involvement of the skin, chest wall or local lymph nodes, and whether the cancer has spread to other organs (called metastasis). In situ carcinomas (eg, ductal carcinoma in situ, lobular carcinoma in situ) are the earliest recognizable breast cancers and rarely spread beyond the breast tissue; more advanced breast cancers, which are referred to as invasive carcinomas, metastasize more often.
The size of the breast tumor, involvement of adjacent lymph nodes, and the presence or absence of spread to other organs are described by the "stage grouping" of a breast cancer, which ranges from stage I to IV. Table 1 summarizes these stages (show table 1). Localized invasive breast cancer generally refers to stage I to IIIA breast cancer. (See "TNM staging classification for breast cancer").
The initial evaluation to determine the stage of a breast cancer usually involves a physical examination, mammogram, chest X-ray, and sometimes CT scans (specialized x-rays) and/or a bone scan. An important component of the staging work-up is an evaluation of the opposite breast. Breast MRI may be recommended to screen the opposite breast for cancer in women who have a breast cancer on one side and who have no abnormalities noted within the opposite breast by either physical examination or mammogram [1,2].
The final stage of the cancer depends upon what is found during microscopic examination of the breast and lymph node tissue after surgery; this is called the pathologic stage, and it is the most accurate indicator of tumor extent and prognosis.
FACTORS AFFECTING TREATMENT — Several factors must be considered when choosing the best treatment for localized breast cancer.
Microscopic findings — There are many different varieties of breast cancer as viewed by the pathologist under the microscope. However, from the standpoint of treatment, the most important distinction is between invasive and noninvasive (in situ) breast cancer. Localized invasive breast cancers are generally approached similarly, whether they are ductal, lobular, or any of the so-called "special types" (tubular, mucinous, colloid, medullary). The surgical treatment of in situ cancers is similar to that of invasive cancers, but postoperative adjuvant systemic therapy is generally not recommended.
Size of the breast tumor — The prognosis of a breast cancer depends upon its size; larger tumors recur more often, and usually require more aggressive treatment. In some cases, chemotherapy may be given before surgery to shrink a large tumor or one that has grown into the chest wall. Inflammatory breast cancer refers to any breast cancer that is associated with an "inflamed" appearance of the breast (show picture 1 and show picture 2); this implies spread of the tumor into the lymph system of the overlying skin. These cancers are treated similarly to large tumors, with chemotherapy preceding surgery or radiation. (See "Patient information: Locally advanced and inflammatory breast cancer").
Spread of cancer cells to the lymph nodes — Fluid from the breast tissue normally drains into lymph nodes located in the armpit (the axilla). These nodes (or glands) are often the first site of spread for breast cancer. If a breast cancer has spread to lymph nodes, it is called node-positive; a cancer that has not spread to the lymph nodes is called node-negative. This is an important distinction because if a breast cancer has spread to the lymph nodes, it is twice as likely to have spread elsewhere, and therefore, to recur over the succeeding years postoperatively.
Most women with node-positive breast cancer should receive adjuvant chemotherapy or hormone therapy after surgery, even if the tumor was completely removed. (See "Patient information: Adjuvant chemotherapy and trastuzumab (Herceptin) for early stage breast cancer").
Tumor markers and prognostic factors — Studies suggest that certain markers or characteristics of the tumor may help determine the prognosis or outcome of breast cancer. Some of these tests are hormone receptors, S phase analysis (a measure of cell proliferation or growth), Her2 status. Levels of plasminogen activators (called uPA and PAI-1) are also measured in certain countries, but not routinely in the United States. All of these tests are performed on the tumor material by the pathologist.
Some of these factors may be associated with a worse outcome and might be used by your doctor to predict the need for further treatment after surgery. Others, such as ER, PgR, and Her2 are associated with a greater likelihood that the cancer may respond to specific types of adjuvant therapy (ie, hormone therapy or antibody therapy) (see below) [3].
Hormone receptors — Some breast cancers have proteins called hormone receptors on their surface; these can be estrogen receptors (ER), progesterone receptors (PgR), or both. If hormone receptors are present in the tumor, women are more likely to benefit from treatments that lower hormone levels or block the actions of these hormones. These treatments are referred to as endocrine or hormone therapies. The test for hormone receptors is usually performed by the pathologist who examines the tumor. (See "Patient information: Adjuvant systemic therapy for hormone-responsive early stage breast cancer in premenopausal women").
Her2 — HER2 is a protein that is present on some breast tumors. Although HER2 is not a very helpful prognostic factor (that is, it does not consistently provide information about whether a tumor is more or less likely to recur), it may help to identify women who are most likely to benefit from specific types of chemotherapy. Furthermore, the presence of HER2 indicates if a woman is likely to benefit from a drug called trastuzumab (Herceptin). (See "Patient information: Adjuvant chemotherapy and trastuzumab (Herceptin) for early stage breast cancer").
Presence of other medical conditions — The presence of other medical conditions may limit the available treatment options for breast cancer.
Personal preferences — Personal preference plays a key role in the treatment of breast cancer. Whenever possible, treatment is individualized to each woman's needs and expectations. Therefore, it is important to meet with a trained medical oncologist to discuss the long term outcomes, benefits of therapy, and risks associated with treatment.
SURGICAL TREATMENT — Surgical removal of the tumor is usually the first step in treating localized breast cancer unless the breast tumor is large or locally invasive. If the cancer is large or locally invasive, another treatment may be recommended before surgery. (See "Patient information: Locally advanced and inflammatory breast cancer", section on "Treatment of locally advanced breast cancer").
There are two options for breast surgery: one involves removing the entire breast (mastectomy) while the other involves removing the tumor and surrounding tissue (lumpectomy). Women who choose lumpectomy usually require additional treatment with radiation to lower the risk of recurrence.
In centers that specialize in breast cancer treatment, approximately 75 percent of women with early stage breast cancer are usually considered appropriate candidates for breast preserving therapy, while the remainder have mastectomy.
MASTECTOMY
Modified radical mastectomy — During a modified radical mastectomy (MRM, show figure 1), the tumor is removed along with all of the breast tissue on the side of the tumor, some of the underlying chest wall tissue, and some of the lymph nodes in the armpit (the axillary lymph nodes). Although the skin of the breast, including the nipple, is removed, the skin covering the chest wall is left intact. The skin is stitched together after removal of the breast. Typically, a draining tube is placed under the skin of the incision for a short time to remove fluid that collects after surgery.
In the United States, modified radical mastectomy is the most common surgery for women with invasive breast cancer.
Total or simple mastectomy — In contrast to MRM, a total or simple mastectomy refers to the removal of the entire breast, not including the arm pit (axillary) lymph nodes. Because the axillary lymph nodes are important for staging and further treatment, total mastectomy has not been considered a standard procedure for women with invasive breast cancer. However, a technique called sentinel node biopsy has allowed total mastectomy to become more popular (see "Sentinel lymph node biopsy" below). Total mastectomy is the treatment of choice for women who are at high risk for a new breast cancer, who therefore decide to have a preventive mastectomy.
Breast reconstruction — Many women choose to have breast reconstruction performed during the same procedure or at a later time. There are several options for reconstruction; frequently, women are evaluated by a plastic or reconstructive surgeon during their initial evaluation to discuss these options prior to the breast surgery.
Complications of mastectomy — Mastectomy is generally a safe surgery, although complications can occur: Collection of fluid (seroma) — Almost all women undergoing mastectomy develop a temporary collection of fluid in the wound, called a seroma. This routine side effect is likely to be more troublesome for women if many lymph nodes must be removed, in obese women, and in women who did not undergo a breast biopsy before the mastectomy. Wound infection — Wound infection occurs in less than 15 percent of women undergoing mastectomy. Infection that occurs soon after mastectomy often appears as an abscess, a collection of pus within the chest wall; infections that occur weeks or months after mastectomy may appear as a cellulitis, an inflammation and infection of the chest wall skin. Arm swelling — Arm swelling (edema) is mostly related to the removal of the axillary lymph nodes, but is also more common in women who undergo mastectomy rather than BCT. Arm edema is more likely to occur in women who undergo removal of the axillary nodes followed by radiation of the armpit area. (See "Patient information: Lymphedema after breast cancer surgery").
Radiation therapy after mastectomy — Radiation therapy of the chest wall after mastectomy may increase the chance of surviving the breast cancer in women who have large tumors (5 cm in size or larger), or who have four or more positive lymph nodes [4]. However, the benefit for women with fewer involved lymph nodes is controversial. The risk of long-term complications of radiation, such as rib fracture or injury to the nerves in the armpit (called the brachial plexus), is less than 5 percent. However, these risks are higher if chemotherapy is given at the same time as radiation or if higher doses of radiation are used.
BREAST CONSERVING THERAPY (BCT) — BCT refers to removal of the part of the breast that contains the tumor, followed by radiation therapy to the remaining breast tissue on the same side.
There are two main types of breast conserving surgery: Lumpectomy — Removal of the tumor and a small amount surrounding breast tissue, show figure 1 Quadrantectomy — Removal of the tumor and about one-fourth of the breast tissue on that side, show figure 1
Lumpectomy is more often used in the United States and Canada, whereas quadrantectomy is more often used in Europe.
Lumpectomy — During lumpectomy, the edges of the removed tissue (called the resection margins) are stained with a special ink and examined under the microscope to check for remaining cancer cells. The surgeon continues to remove additional tissue until no remaining cancer cells are detected by the pathologist (the pathologist examines the tissue while the patient has surgery). During the lumpectomy procedure, lymph nodes in the armpit are usually removed to check for the spread of cancer cells to this area.
Complications of lumpectomy — Lumpectomy is generally a safe surgery, although some complications are possible: Breast cellulitis — Breast cellulitis is an inflammation and infection of the breast tissue. Cellulitis after lumpectomy appears to be related to the presence of bruises after surgery, the collection of fluid in the lymphatic system, and the removal of a large amount of breast tissue. Breast abscess — A breast abscess is a collection of pus within the breast tissue, tends to occur, on average, about five months after BCT. This complication is more common in women following the removal of large amounts of breast tissue.
Radiation therapy
What is radiation therapy? — Radiation therapy (RT) refers to the exposure of a tumor to high-energy x-rays in order to slow or stop its growth. Exposure to x-rays damages cells. Unlike normal cells, cancer cells cannot repair the damage caused by exposure to x-rays, particularly when it is administered over several days. This prevents the cancer cells from growing further and causes them to eventually die.
RT for breast cancer is given as external beam radiation therapy, meaning that the radiation beam is generated by a machine that is outside the patient. The radiation is delivered to the patient, who is usually lying on a table underneath the machine.
Exposure to the beam typically takes only a few seconds (similar to having an x-ray). In general, treatment is repeated five days per week for approximately five to six weeks. Treatment cannot be given over a shorter period because the higher daily doses would cause too many side effects.
Radiation therapy is recommended for the remaining breast tissue on the same side of the tumor after breast conserving surgery. The goal of this radiation therapy is to kill any remaining cancer cells that were not removed during surgery. An extra dose of radiation (called a radiation boost) is often given to the area where the tumor was located.
Benefit of radiation therapy — Studies confirm that radiation plays a critical role in preventing a local recurrence of breast cancer after BCT and in improving survival. In many studies of women undergoing lumpectomy for localized breast cancer, cancer recurred within 20 years in 7 to 14 percent of women who received radiation therapy compared with 26 to 39 percent of women who did not receive this therapy [4-6]. Thus, a local recurrence is approximately three times more likely in women who do not undergo RT. Furthermore, women who receive radiation therapy are also more likely to survive their cancer [4,6].
There is currently no reliable method to identify women who will not have a recurrence if they skip radiation. Therefore, radiation is generally recommended for all women after breast conserving surgery. One possible exception is women over the age of 70 who have small (<2 cm) ER-positive breast cancers; these women are usually initially treated with hormone therapy (eg, tamoxifen) and radiation treatment is not given.
New radiation therapy delivery systems — New ways to give radiotherapy are currently under study. These include short course therapy (giving the treatment over five to ten days instead of four to six weeks), brachytherapy (placing the radiation source directly in the tissues of the breast for a few days), and even intraoperative therapy. Currently, these methods of administering radiation therapy are considered investigational.
Cosmetic results of BCT — With modern surgical techniques, breast conserving therapy has excellent cosmetic results (ie, the treated and untreated breast are almost identical) or good cosmetic results (ie, only slight differences between the treated and untreated breast).
The effects of BCT on the appearance of the breast usually take about three years to stabilize. Factors such as weight gain and the normal age-related sagging of breast tissue may further affect the symmetry of the two breasts.
Several other factors influence the cosmetic results of BCT: Surgical factors — The amount of breast tissue removed during surgery plays a key role in the cosmetic result of BCT. Lumpectomy generally produces a better cosmetic result than quadrantectomy.
Other surgical factors that may affect the cosmetic appearance of the breast after BCT include the size and location of the incision, the postoperative care of the space left by lumpectomy, and the extent of surgery required to remove lymph nodes. Individual factors — Several individual factors also affect the cosmetic result of BCT. These factors include the size of the breast, the size of the tumor, the depth of the tumor within the breast, and the quadrant in which the tumor was located. Use of adjuvant chemotherapy — The use of adjuvant chemotherapy and its timing may affect the cosmetic result of BCT. In one study in women who underwent BCT, the cosmetic results were poorer in women who received radiation therapy and chemotherapy at the same time (concurrent treatment) compared to women receiving chemotherapy followed by radiation therapy (sequential treatment) [7]. This is one of the reasons why chemotherapy is generally given before radiation therapy. (See "Patient information: Adjuvant chemotherapy and trastuzumab (Herceptin) for early stage breast cancer").
Complications following BCT — Following BCT, the following complications may occur: Arm problems — Among women who undergo BCT and axillary lymph node removal, one in five develop arm edema; this is less than the number of women who develop lymphedema after mastectomy [8]. The likelihood of arm swelling is twice as high if the armpit area is radiated after a lymph node dissection. The likelihood of arm edema is also related to the extent of the axillary dissection that is done by the surgeon to evaluate the lymph nodes. (See "Patient information: Lymphedema after breast cancer surgery").
One-half of women may have some temporary loss of shoulder movement, and less than 5 percent of women have damage to the nerves in the armpit (called the brachial plexus) that control arm movement and sensation in the arm. Rib fracture — In less than 5 percent of women who undergo BCT, radiation causes changes in the bones of the chest wall that increase the risk for rib fractures.
MASTECTOMY VERSUS BREAST PRESERVING THERAPY — Numerous studies show that women with localized breast cancer are equally likely to survive their cancer whether they are treated with breast conserving therapy (BCT) or a mastectomy [4,9]. However, it is estimated that fewer than 60 percent of women with early-stage breast cancer are treated with BCT. Some evidence suggests that clinicians encourage women to select mastectomy over BCT, and that women themselves prefer mastectomy to BCT [10]. Furthermore, the selection of BCT is influenced by geographic and socioeconomic factors as well.
Despite the equivalent survival, several factors are taken into consideration when determining whether BCT or mastectomy is a better option for a woman with localized breast cancer.
Medical history and physical examination — A medical history and physical exam are useful to determine a woman's overall health and the presence of other medical conditions. The presence of certain conditions may make BCT or mastectomy a better treatment option. A woman's age alone does not determine if BCT or mastectomy is a better choice.
Results of mammography — A preoperative mammogram is essential for determining the size and extent of the tumor and other tumor features that may affect the choice between BCT or mastectomy.
Microscopic examination of the tumor — Microscopic examination of the tissue removed during a biopsy or during surgery may identify features that affect the recommendation for BCT versus mastectomy. One of these features is the presence of residual cancer cells at the margins. If many residual cancer cells are present after a large amount of tissue has been removed, mastectomy may be preferable.
Individual needs and expectations — Each woman should discuss her expectations and concerns about preserving her breast with her doctor. It is particularly important to consider how the choice of BCT or mastectomy is likely to affect a woman's confidence in the effectiveness of cancer treatment as well as her self-esteem, sexuality, and overall quality of life. The discussion regarding the benefits and risks should include several essential points: The long-term survival after breast cancer The possibility and consequences of a local recurrence The psychological adjustment to treatment (including the fear that cancer will return) The likely cosmetic results Sexuality after treatment
For most women, the likelihood of surviving localized breast cancer is the same with mastectomy or BCT [4,9]; in contrast, the choice of mastectomy versus BCT may have a considerable effect on a woman's quality of life. The overall experience of having breast cancer is equally distressing for women who choose BCT and for those who choose mastectomy. However, compared to women who choose mastectomy, women who choose BCT tend to have a more positive body image and experience fewer changes in their feelings of sexual desirability.
Certain clinical factors clearly favor mastectomy over BCT for medical reasons in individual women. These include: The presence of two or more separate tumors in different areas of the breast Diffuse spread of the tumor in the breast tissue Previous radiation of the breast or chest, which makes future radiation inadvisable Pregnancy in the first or second trimester, which makes radiation inadvisable The presence of many residual cancer cells during breast conserving surgery despite the removal of a large amount of tissue
Certain clinical factors somewhat favor mastectomy over BCT for medical reasons in individual women, although exceptions exist: The presence of certain connective tissue (autoimmune) diseases that are associated with marked side effects from radiation therapy; women with scleroderma and active systemic lupus erythematosus (SLE) are usually advised to select mastectomy over BCT, though women with rheumatoid arthritis can safely undergo radiation therapy and can therefore choose between BCT and mastectomy The presence of several adjacent tumors and the presence of calcium deposits in the same area as the breast tumor A larger tumor size; mastectomy is usually recommended for tumors larger than about two inches and for women who have tumors that are large relative to their breast size The size and shape of the breast; It may be difficult to consistently target radiation in women with very large or pendulous breasts, and these women may be advised to select mastectomy over BCT
Several factors do not play a role in the choice between BCT and mastectomy: The spread of cancer cells to lymph nodes in the armpit The specific location of the tumor within the breast; however, certain tumor locations may reduce the cosmetic results of BCT A family history of breast cancer A high likelihood that cancer will metastasize (recur elsewhere in the body); however, an increased risk of metastases indicates the need for adjuvant therapies
MANAGEMENT OF AXILLARY LYMPH NODES — Although some enlarged lymph nodes can be felt on physical examination, surgery is the only accurate way to determine if the cancer has spread to the lymph nodes in the axilla, or armpit. A complete removal of the axillary lymph nodes, an axillary lymph node dissection (ALND), has traditionally been a routine component of the management of early stage breast cancer for women undergoing both mastectomy and BCT. However, considerable controversy exists regarding whether aggressive treatment of draining nodal areas is indicated. Clearly, the information gained from ALND is prognostic. Furthermore, undertreatment of positive axillary lymph nodes increases the risk of a local recurrence. However, it is unclear if more aggressive treatment of the axillary nodes improves survival. Regardless, more aggressive lymph node treatment (surgery and/or radiation) increases the risk of complications.
The extent of an ALND is determined by the number and location of the nodes removed. The most common complication of ALND is lymphedema, the severity of which depends upon the extent of the ALND. (See "Patient information: Lymphedema after breast cancer surgery"). The desire to accurately identify women who have involved lymph nodes while minimizing the chance of arm swelling has led to the development of the sentinel node biopsy technique.
Sentinel lymph node biopsy — Sentinel node biopsy is an alternative to complete removal of the axillary lymph nodes that has significantly fewer arm complications.
The concept is based on the premise that tumor cells from a breast tumor first involve one or a few lymph nodes before involving lymph nodes in other areas or spreading to distant organs. To identify this sentinel node, the surgeon injects blue dye, a radioactive material, or a combination of both into the area surrounding the tumor, where it enters lymphatic channels and then flows to lymph nodes.
If a SLN is identified, it is removed and examined under the microscope. If this node is does not contain any cancer cells, there is a very small chance that other axillary nodes will be positive and a full ALND is not necessary [11]. In contrast, if the SLN is positive, there is a good chance that other nodes will contain tumor cells, and a full ALND is usually performed.
The main problem with SLN biopsy is that a SLN may be "falsely" negative, meaning that the axillary lymph nodes actually contain tumor cells when the SLN predicts that they do not. The likelihood of a false-negative SLN is related to a surgeon's experience with this procedure. In experienced hands, the risk of a false positive is about 5 percent [12].
Guidelines from the American Society of Clinical Oncology support the use of SLN biopsy as an alternative to full ALND in many patients with early stage breast cancer as long as there is no suspicion from the physical examination that the axillary nodes may be involved with tumor spread [11].
RECURRENCE AFTER BCT — A local recurrence refers to a return of cancer in the breast tissue or the surrounding chest wall. After mastectomy, local recurrences are in the chest wall because there is no remaining breast tissue; following BCT, a recurrence is usually within the remaining breast tissue.
In women with stage I or II breast cancer, local recurrence develops in 7 to 20 percent of women treated with BCT, and in 4 to 14 percent of women treated with mastectomy. However, the time course of recurrence is different. A local recurrence is often delayed for many years in women treated with BCT, whereas a local recurrence usually occurs within three years in women treated with mastectomy.
It is important to note that BCT does not completely prevent new breast cancers from arising in the remaining breast tissue. In women treated with BCT, the risk of a new, unrelated tumor on the same side is about 1 percent per year (eg, 13 percent risk over 15 years following the procedure).
Surveillance — Women who have undergone BCT must continue to perform breast self-exams and undergo screening of both breasts with mammography. A summary of the American Society of Clinical Oncology's recommendations for surveillance after breast cancer treatment is provided in table 2 (show table 2).
Risk factors — The likelihood that breast cancer will recur locally after BCT is influenced by individual factors, tumor factors, and treatment factors.
Individual factors — A woman's age appears to influence the risk of a local recurrence after BCT. Women who are age 40 years or younger at the time of BCT are more likely than older women to have a local recurrence after BCT. Other studies suggest that younger women may also be more likely to have a local recurrence after mastectomy. Thus, young age should not be used as a factor in choosing one treatment over another, but instead should be used as an indicator of a higher risk of a local recurrence.
Tumor factors — The likelihood of a local recurrence after BCT is also influenced by two tumor-related factors: Residual cancer cells at the edge of the wound — The presence of residual cancer cells at the edge of the wound (called the resection margin) increases the likelihood of a local recurrence after BCT. In one study, the rate of local recurrence after BCT was 7 percent in women in whom no residual cells are found, compared to 18 percent in women in whom residual cancer cells were found [13]. Although the surgeon will try to remove all of these cells during surgery, residual cells are sometimes detected after surgery on more detailed microscopic examination. Presence of cancer cells within ducts — The presence of cancer cells within many ducts of the removed breast tissue, termed an extensive intraductal component, is useful for assessing the likelihood of a local recurrence. A local recurrence is more likely when cancer cells are present in many ducts within the tumor or within the normal breast tissue, if tumor cells remain at the margin of resection. Certain findings on mammograms taken before surgery often alert the surgeon to the presence of cancer cells in ducts. In such cases, particular care must be taken by the surgeon to make certain that no remaining tumor cells are present at the surgical margins.
Treatment factors — Three treatment factors influence the likelihood of a local recurrence after BCT: Extent of surgery — Local recurrence of breast cancer after BCT is less likely when a greater amount of breast tissue is removed during surgery. Radiation boost — A radiation boost refers to the delivery of an extra dose of radiation to the area of the breast where the tumor was located. Some, but not all studies suggest that a radiation boost slightly reduces the likelihood of a local recurrence of breast cancer, although this boost may slightly reduce the cosmetic results of BCT. Chemotherapy or hormone therapy — Chemotherapy and/or hormonal therapy are often recommended following surgery for localized breast cancer. The addition of these therapies to BCT further reduces the likelihood of a local recurrence, although not all women will need both of these therapies.
As an example, in one study of women with node-negative, ER-negative breast cancer, women were treated with chemotherapy or no chemotherapy after BCT [14]. Cancer recurred locally within eight years in 2.6 percent of the women treated with chemotherapy and in 13.4 percent of the women who were not treated with chemotherapy.
In a second study in women with node-negative, ER-positive breast cancer, women were treated with tamoxifen or a placebo after BCT [15]. Cancer recurred locally within ten years in 4.3 percent of the women treated with tamoxifen, and in 14.7 percent of the women who were treated a placebo.
Treatment — Many women who have a local recurrence can undergo a "salvage" mastectomy, and still have a chance to be cured from their cancer if there is no further spread.
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Cancer Institute
1-800-4-CANCER
(www.nci.nih.gov)
People Living With Cancer: The official patient information
website of the American Society of Clinical Oncology
(www.plwc.org/portal/site/PLWC)
National Comprehensive Cancer Network
(www.nccn.org/patients/patient_gls.asp)
American Cancer Society
1-800-ACS-2345
(www.cancer.org)
National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
Susan G. Komen Breast Cancer Foundation
(www.komen.org)
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Saslow, D, Boetes, C, Burke, W, et al. American Cancer Society guidelines for breast cancer screening with MRI as an adjunct to mammography. CA Cancer J Clin 2007; 57:75.
2. Lehman, CD, Gatsonis, C, Kuhl, CK, et al. MRI evaluation of the contralateral breast in women with recently diagnosed breast cancer. N Engl J Med 2007; 356:1295.
3. Yamauchi, H, Stearns, V, Hayes, DF. When is a tumor marker ready for prime time? A case study of c-erbB-2 as a predictive factor in breast cancer. J Clin Oncol 2001; 19:2334.
4. Clarke, M, Collins, R, Darby, S, et al. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005; 366:2087.
5. Fisher, B, Anderson, S, Bryant, J, et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med 2002; 347:1233.
6. Vinh-Hung, V, Verschraegen, C. Breast-conserving surgery with or without radiotherapy: pooled-analysis for risks of ipsilateral breast tumor recurrence and mortality. J Natl Cancer Inst 2004; 96:115.
7. Abner, AL, Recht, A, Vicini, FA, et al. Cosmetic results after surgery, chemotherapy, and radiation therapy for early breast cancer. Int J Radiat Oncol Biol Phys 1991; 21:331.
8. Erickson, VS, Pearson, ML, Ganz, PA, et al. Arm edema in breast cancer patients. J Natl Cancer Inst 2001; 93:96.
9. NIH Consensus Development Conference statement on the treatment of early-stage breast cancer. Oncology (Huntingt) 1991; 5:120.
10. Morrow, M, White, J, Moughan, J, et al. Factors predicting the use of breast-conserving therapy in stage I and II breast carcinoma. J Clin Oncol 2001; 19:2254.
11. Lyman, GH, Giuliano, AE, Somerfield, MR, et al. American Society of Clinical Oncology Guideline Recommendations for Sentinel Lymph Node Biopsy in Early-Stage Breast Cancer. J Clin Oncol 2005; 23:7703.
12. Guidelines from the American Society of Breast Surgeons available online at www.breastsurgeons.org/officialstmts/sentinel.shtml (accessed September 13, 2005).
13. Park, CC, Mitsumori, M, Nixon, A, et al. Outcome at 8 years after breast-conserving surgery and radiation therapy for invasive breast cancer: influence of margin status and systemic therapy on local recurrence. J Clin Oncol 2000; 18:1668.
14. Fisher, B, Dignam, J, Mamounas, EP, et al. Sequential methotrexate and fluorouracil for the treatment of node-negative breast cancer patients with estrogen receptor-negative tumors: eight-year results from National Surgical Adjuvant Breast and Bowel Project (NSABP) B-13 and first report of findings from NSABP B-19 comparing methotrexate and fluorouracil with conventional cyclophosphamide, methotrexate, and fluorouracil. J Clin Oncol 1996; 14:1982.
15. Fisher, B, Dignam, J, Bryant, J, et al. Five versus more than five years of tamoxifen therapy for breast cancer patients with negative lymph nodes and estrogen receptor-positive tumors. J Natl Cancer Inst 1996; 88:1529.
Two surgical options are available for treating localized breast cancer: mastectomy (removal of the breast) and breast preserving therapy. After either surgery, systemic (bodywide) therapy is often recommended to decrease the likelihood that the cancer will return. The options for systemic therapy include chemotherapy, hormone therapy, or antibody therapy. (See "Patient information: Adjuvant chemotherapy and trastuzumab (Herceptin) for early stage breast cancer").
The treatment of localized breast cancer must be individualized and is based upon several factors. Optimal management requires collaboration between surgeons and physicians who specialize in radiation and medical oncology. Each woman should carefully discuss the available treatment options with her doctors to determine which is the best choice for her.
BREAST CANCER STAGING — Treatment and prognosis (outcome) depend upon the stage of the cancer, which is based upon the size of the tumor, involvement of the skin, chest wall or local lymph nodes, and whether the cancer has spread to other organs (called metastasis). In situ carcinomas (eg, ductal carcinoma in situ, lobular carcinoma in situ) are the earliest recognizable breast cancers and rarely spread beyond the breast tissue; more advanced breast cancers, which are referred to as invasive carcinomas, metastasize more often.
The size of the breast tumor, involvement of adjacent lymph nodes, and the presence or absence of spread to other organs are described by the "stage grouping" of a breast cancer, which ranges from stage I to IV. Table 1 summarizes these stages (show table 1). Localized invasive breast cancer generally refers to stage I to IIIA breast cancer. (See "TNM staging classification for breast cancer").
The initial evaluation to determine the stage of a breast cancer usually involves a physical examination, mammogram, chest X-ray, and sometimes CT scans (specialized x-rays) and/or a bone scan. An important component of the staging work-up is an evaluation of the opposite breast. Breast MRI may be recommended to screen the opposite breast for cancer in women who have a breast cancer on one side and who have no abnormalities noted within the opposite breast by either physical examination or mammogram [1,2].
The final stage of the cancer depends upon what is found during microscopic examination of the breast and lymph node tissue after surgery; this is called the pathologic stage, and it is the most accurate indicator of tumor extent and prognosis.
FACTORS AFFECTING TREATMENT — Several factors must be considered when choosing the best treatment for localized breast cancer.
Microscopic findings — There are many different varieties of breast cancer as viewed by the pathologist under the microscope. However, from the standpoint of treatment, the most important distinction is between invasive and noninvasive (in situ) breast cancer. Localized invasive breast cancers are generally approached similarly, whether they are ductal, lobular, or any of the so-called "special types" (tubular, mucinous, colloid, medullary). The surgical treatment of in situ cancers is similar to that of invasive cancers, but postoperative adjuvant systemic therapy is generally not recommended.
Size of the breast tumor — The prognosis of a breast cancer depends upon its size; larger tumors recur more often, and usually require more aggressive treatment. In some cases, chemotherapy may be given before surgery to shrink a large tumor or one that has grown into the chest wall. Inflammatory breast cancer refers to any breast cancer that is associated with an "inflamed" appearance of the breast (show picture 1 and show picture 2); this implies spread of the tumor into the lymph system of the overlying skin. These cancers are treated similarly to large tumors, with chemotherapy preceding surgery or radiation. (See "Patient information: Locally advanced and inflammatory breast cancer").
Spread of cancer cells to the lymph nodes — Fluid from the breast tissue normally drains into lymph nodes located in the armpit (the axilla). These nodes (or glands) are often the first site of spread for breast cancer. If a breast cancer has spread to lymph nodes, it is called node-positive; a cancer that has not spread to the lymph nodes is called node-negative. This is an important distinction because if a breast cancer has spread to the lymph nodes, it is twice as likely to have spread elsewhere, and therefore, to recur over the succeeding years postoperatively.
Most women with node-positive breast cancer should receive adjuvant chemotherapy or hormone therapy after surgery, even if the tumor was completely removed. (See "Patient information: Adjuvant chemotherapy and trastuzumab (Herceptin) for early stage breast cancer").
Tumor markers and prognostic factors — Studies suggest that certain markers or characteristics of the tumor may help determine the prognosis or outcome of breast cancer. Some of these tests are hormone receptors, S phase analysis (a measure of cell proliferation or growth), Her2 status. Levels of plasminogen activators (called uPA and PAI-1) are also measured in certain countries, but not routinely in the United States. All of these tests are performed on the tumor material by the pathologist.
Some of these factors may be associated with a worse outcome and might be used by your doctor to predict the need for further treatment after surgery. Others, such as ER, PgR, and Her2 are associated with a greater likelihood that the cancer may respond to specific types of adjuvant therapy (ie, hormone therapy or antibody therapy) (see below) [3].
Hormone receptors — Some breast cancers have proteins called hormone receptors on their surface; these can be estrogen receptors (ER), progesterone receptors (PgR), or both. If hormone receptors are present in the tumor, women are more likely to benefit from treatments that lower hormone levels or block the actions of these hormones. These treatments are referred to as endocrine or hormone therapies. The test for hormone receptors is usually performed by the pathologist who examines the tumor. (See "Patient information: Adjuvant systemic therapy for hormone-responsive early stage breast cancer in premenopausal women").
Her2 — HER2 is a protein that is present on some breast tumors. Although HER2 is not a very helpful prognostic factor (that is, it does not consistently provide information about whether a tumor is more or less likely to recur), it may help to identify women who are most likely to benefit from specific types of chemotherapy. Furthermore, the presence of HER2 indicates if a woman is likely to benefit from a drug called trastuzumab (Herceptin). (See "Patient information: Adjuvant chemotherapy and trastuzumab (Herceptin) for early stage breast cancer").
Presence of other medical conditions — The presence of other medical conditions may limit the available treatment options for breast cancer.
Personal preferences — Personal preference plays a key role in the treatment of breast cancer. Whenever possible, treatment is individualized to each woman's needs and expectations. Therefore, it is important to meet with a trained medical oncologist to discuss the long term outcomes, benefits of therapy, and risks associated with treatment.
SURGICAL TREATMENT — Surgical removal of the tumor is usually the first step in treating localized breast cancer unless the breast tumor is large or locally invasive. If the cancer is large or locally invasive, another treatment may be recommended before surgery. (See "Patient information: Locally advanced and inflammatory breast cancer", section on "Treatment of locally advanced breast cancer").
There are two options for breast surgery: one involves removing the entire breast (mastectomy) while the other involves removing the tumor and surrounding tissue (lumpectomy). Women who choose lumpectomy usually require additional treatment with radiation to lower the risk of recurrence.
In centers that specialize in breast cancer treatment, approximately 75 percent of women with early stage breast cancer are usually considered appropriate candidates for breast preserving therapy, while the remainder have mastectomy.
MASTECTOMY
Modified radical mastectomy — During a modified radical mastectomy (MRM, show figure 1), the tumor is removed along with all of the breast tissue on the side of the tumor, some of the underlying chest wall tissue, and some of the lymph nodes in the armpit (the axillary lymph nodes). Although the skin of the breast, including the nipple, is removed, the skin covering the chest wall is left intact. The skin is stitched together after removal of the breast. Typically, a draining tube is placed under the skin of the incision for a short time to remove fluid that collects after surgery.
In the United States, modified radical mastectomy is the most common surgery for women with invasive breast cancer.
Total or simple mastectomy — In contrast to MRM, a total or simple mastectomy refers to the removal of the entire breast, not including the arm pit (axillary) lymph nodes. Because the axillary lymph nodes are important for staging and further treatment, total mastectomy has not been considered a standard procedure for women with invasive breast cancer. However, a technique called sentinel node biopsy has allowed total mastectomy to become more popular (see "Sentinel lymph node biopsy" below). Total mastectomy is the treatment of choice for women who are at high risk for a new breast cancer, who therefore decide to have a preventive mastectomy.
Breast reconstruction — Many women choose to have breast reconstruction performed during the same procedure or at a later time. There are several options for reconstruction; frequently, women are evaluated by a plastic or reconstructive surgeon during their initial evaluation to discuss these options prior to the breast surgery.
Complications of mastectomy — Mastectomy is generally a safe surgery, although complications can occur: Collection of fluid (seroma) — Almost all women undergoing mastectomy develop a temporary collection of fluid in the wound, called a seroma. This routine side effect is likely to be more troublesome for women if many lymph nodes must be removed, in obese women, and in women who did not undergo a breast biopsy before the mastectomy. Wound infection — Wound infection occurs in less than 15 percent of women undergoing mastectomy. Infection that occurs soon after mastectomy often appears as an abscess, a collection of pus within the chest wall; infections that occur weeks or months after mastectomy may appear as a cellulitis, an inflammation and infection of the chest wall skin. Arm swelling — Arm swelling (edema) is mostly related to the removal of the axillary lymph nodes, but is also more common in women who undergo mastectomy rather than BCT. Arm edema is more likely to occur in women who undergo removal of the axillary nodes followed by radiation of the armpit area. (See "Patient information: Lymphedema after breast cancer surgery").
Radiation therapy after mastectomy — Radiation therapy of the chest wall after mastectomy may increase the chance of surviving the breast cancer in women who have large tumors (5 cm in size or larger), or who have four or more positive lymph nodes [4]. However, the benefit for women with fewer involved lymph nodes is controversial. The risk of long-term complications of radiation, such as rib fracture or injury to the nerves in the armpit (called the brachial plexus), is less than 5 percent. However, these risks are higher if chemotherapy is given at the same time as radiation or if higher doses of radiation are used.
BREAST CONSERVING THERAPY (BCT) — BCT refers to removal of the part of the breast that contains the tumor, followed by radiation therapy to the remaining breast tissue on the same side.
There are two main types of breast conserving surgery: Lumpectomy — Removal of the tumor and a small amount surrounding breast tissue, show figure 1 Quadrantectomy — Removal of the tumor and about one-fourth of the breast tissue on that side, show figure 1
Lumpectomy is more often used in the United States and Canada, whereas quadrantectomy is more often used in Europe.
Lumpectomy — During lumpectomy, the edges of the removed tissue (called the resection margins) are stained with a special ink and examined under the microscope to check for remaining cancer cells. The surgeon continues to remove additional tissue until no remaining cancer cells are detected by the pathologist (the pathologist examines the tissue while the patient has surgery). During the lumpectomy procedure, lymph nodes in the armpit are usually removed to check for the spread of cancer cells to this area.
Complications of lumpectomy — Lumpectomy is generally a safe surgery, although some complications are possible: Breast cellulitis — Breast cellulitis is an inflammation and infection of the breast tissue. Cellulitis after lumpectomy appears to be related to the presence of bruises after surgery, the collection of fluid in the lymphatic system, and the removal of a large amount of breast tissue. Breast abscess — A breast abscess is a collection of pus within the breast tissue, tends to occur, on average, about five months after BCT. This complication is more common in women following the removal of large amounts of breast tissue.
Radiation therapy
What is radiation therapy? — Radiation therapy (RT) refers to the exposure of a tumor to high-energy x-rays in order to slow or stop its growth. Exposure to x-rays damages cells. Unlike normal cells, cancer cells cannot repair the damage caused by exposure to x-rays, particularly when it is administered over several days. This prevents the cancer cells from growing further and causes them to eventually die.
RT for breast cancer is given as external beam radiation therapy, meaning that the radiation beam is generated by a machine that is outside the patient. The radiation is delivered to the patient, who is usually lying on a table underneath the machine.
Exposure to the beam typically takes only a few seconds (similar to having an x-ray). In general, treatment is repeated five days per week for approximately five to six weeks. Treatment cannot be given over a shorter period because the higher daily doses would cause too many side effects.
Radiation therapy is recommended for the remaining breast tissue on the same side of the tumor after breast conserving surgery. The goal of this radiation therapy is to kill any remaining cancer cells that were not removed during surgery. An extra dose of radiation (called a radiation boost) is often given to the area where the tumor was located.
Benefit of radiation therapy — Studies confirm that radiation plays a critical role in preventing a local recurrence of breast cancer after BCT and in improving survival. In many studies of women undergoing lumpectomy for localized breast cancer, cancer recurred within 20 years in 7 to 14 percent of women who received radiation therapy compared with 26 to 39 percent of women who did not receive this therapy [4-6]. Thus, a local recurrence is approximately three times more likely in women who do not undergo RT. Furthermore, women who receive radiation therapy are also more likely to survive their cancer [4,6].
There is currently no reliable method to identify women who will not have a recurrence if they skip radiation. Therefore, radiation is generally recommended for all women after breast conserving surgery. One possible exception is women over the age of 70 who have small (<2 cm) ER-positive breast cancers; these women are usually initially treated with hormone therapy (eg, tamoxifen) and radiation treatment is not given.
New radiation therapy delivery systems — New ways to give radiotherapy are currently under study. These include short course therapy (giving the treatment over five to ten days instead of four to six weeks), brachytherapy (placing the radiation source directly in the tissues of the breast for a few days), and even intraoperative therapy. Currently, these methods of administering radiation therapy are considered investigational.
Cosmetic results of BCT — With modern surgical techniques, breast conserving therapy has excellent cosmetic results (ie, the treated and untreated breast are almost identical) or good cosmetic results (ie, only slight differences between the treated and untreated breast).
The effects of BCT on the appearance of the breast usually take about three years to stabilize. Factors such as weight gain and the normal age-related sagging of breast tissue may further affect the symmetry of the two breasts.
Several other factors influence the cosmetic results of BCT: Surgical factors — The amount of breast tissue removed during surgery plays a key role in the cosmetic result of BCT. Lumpectomy generally produces a better cosmetic result than quadrantectomy.
Other surgical factors that may affect the cosmetic appearance of the breast after BCT include the size and location of the incision, the postoperative care of the space left by lumpectomy, and the extent of surgery required to remove lymph nodes. Individual factors — Several individual factors also affect the cosmetic result of BCT. These factors include the size of the breast, the size of the tumor, the depth of the tumor within the breast, and the quadrant in which the tumor was located. Use of adjuvant chemotherapy — The use of adjuvant chemotherapy and its timing may affect the cosmetic result of BCT. In one study in women who underwent BCT, the cosmetic results were poorer in women who received radiation therapy and chemotherapy at the same time (concurrent treatment) compared to women receiving chemotherapy followed by radiation therapy (sequential treatment) [7]. This is one of the reasons why chemotherapy is generally given before radiation therapy. (See "Patient information: Adjuvant chemotherapy and trastuzumab (Herceptin) for early stage breast cancer").
Complications following BCT — Following BCT, the following complications may occur: Arm problems — Among women who undergo BCT and axillary lymph node removal, one in five develop arm edema; this is less than the number of women who develop lymphedema after mastectomy [8]. The likelihood of arm swelling is twice as high if the armpit area is radiated after a lymph node dissection. The likelihood of arm edema is also related to the extent of the axillary dissection that is done by the surgeon to evaluate the lymph nodes. (See "Patient information: Lymphedema after breast cancer surgery").
One-half of women may have some temporary loss of shoulder movement, and less than 5 percent of women have damage to the nerves in the armpit (called the brachial plexus) that control arm movement and sensation in the arm. Rib fracture — In less than 5 percent of women who undergo BCT, radiation causes changes in the bones of the chest wall that increase the risk for rib fractures.
MASTECTOMY VERSUS BREAST PRESERVING THERAPY — Numerous studies show that women with localized breast cancer are equally likely to survive their cancer whether they are treated with breast conserving therapy (BCT) or a mastectomy [4,9]. However, it is estimated that fewer than 60 percent of women with early-stage breast cancer are treated with BCT. Some evidence suggests that clinicians encourage women to select mastectomy over BCT, and that women themselves prefer mastectomy to BCT [10]. Furthermore, the selection of BCT is influenced by geographic and socioeconomic factors as well.
Despite the equivalent survival, several factors are taken into consideration when determining whether BCT or mastectomy is a better option for a woman with localized breast cancer.
Medical history and physical examination — A medical history and physical exam are useful to determine a woman's overall health and the presence of other medical conditions. The presence of certain conditions may make BCT or mastectomy a better treatment option. A woman's age alone does not determine if BCT or mastectomy is a better choice.
Results of mammography — A preoperative mammogram is essential for determining the size and extent of the tumor and other tumor features that may affect the choice between BCT or mastectomy.
Microscopic examination of the tumor — Microscopic examination of the tissue removed during a biopsy or during surgery may identify features that affect the recommendation for BCT versus mastectomy. One of these features is the presence of residual cancer cells at the margins. If many residual cancer cells are present after a large amount of tissue has been removed, mastectomy may be preferable.
Individual needs and expectations — Each woman should discuss her expectations and concerns about preserving her breast with her doctor. It is particularly important to consider how the choice of BCT or mastectomy is likely to affect a woman's confidence in the effectiveness of cancer treatment as well as her self-esteem, sexuality, and overall quality of life. The discussion regarding the benefits and risks should include several essential points: The long-term survival after breast cancer The possibility and consequences of a local recurrence The psychological adjustment to treatment (including the fear that cancer will return) The likely cosmetic results Sexuality after treatment
For most women, the likelihood of surviving localized breast cancer is the same with mastectomy or BCT [4,9]; in contrast, the choice of mastectomy versus BCT may have a considerable effect on a woman's quality of life. The overall experience of having breast cancer is equally distressing for women who choose BCT and for those who choose mastectomy. However, compared to women who choose mastectomy, women who choose BCT tend to have a more positive body image and experience fewer changes in their feelings of sexual desirability.
Certain clinical factors clearly favor mastectomy over BCT for medical reasons in individual women. These include: The presence of two or more separate tumors in different areas of the breast Diffuse spread of the tumor in the breast tissue Previous radiation of the breast or chest, which makes future radiation inadvisable Pregnancy in the first or second trimester, which makes radiation inadvisable The presence of many residual cancer cells during breast conserving surgery despite the removal of a large amount of tissue
Certain clinical factors somewhat favor mastectomy over BCT for medical reasons in individual women, although exceptions exist: The presence of certain connective tissue (autoimmune) diseases that are associated with marked side effects from radiation therapy; women with scleroderma and active systemic lupus erythematosus (SLE) are usually advised to select mastectomy over BCT, though women with rheumatoid arthritis can safely undergo radiation therapy and can therefore choose between BCT and mastectomy The presence of several adjacent tumors and the presence of calcium deposits in the same area as the breast tumor A larger tumor size; mastectomy is usually recommended for tumors larger than about two inches and for women who have tumors that are large relative to their breast size The size and shape of the breast; It may be difficult to consistently target radiation in women with very large or pendulous breasts, and these women may be advised to select mastectomy over BCT
Several factors do not play a role in the choice between BCT and mastectomy: The spread of cancer cells to lymph nodes in the armpit The specific location of the tumor within the breast; however, certain tumor locations may reduce the cosmetic results of BCT A family history of breast cancer A high likelihood that cancer will metastasize (recur elsewhere in the body); however, an increased risk of metastases indicates the need for adjuvant therapies
MANAGEMENT OF AXILLARY LYMPH NODES — Although some enlarged lymph nodes can be felt on physical examination, surgery is the only accurate way to determine if the cancer has spread to the lymph nodes in the axilla, or armpit. A complete removal of the axillary lymph nodes, an axillary lymph node dissection (ALND), has traditionally been a routine component of the management of early stage breast cancer for women undergoing both mastectomy and BCT. However, considerable controversy exists regarding whether aggressive treatment of draining nodal areas is indicated. Clearly, the information gained from ALND is prognostic. Furthermore, undertreatment of positive axillary lymph nodes increases the risk of a local recurrence. However, it is unclear if more aggressive treatment of the axillary nodes improves survival. Regardless, more aggressive lymph node treatment (surgery and/or radiation) increases the risk of complications.
The extent of an ALND is determined by the number and location of the nodes removed. The most common complication of ALND is lymphedema, the severity of which depends upon the extent of the ALND. (See "Patient information: Lymphedema after breast cancer surgery"). The desire to accurately identify women who have involved lymph nodes while minimizing the chance of arm swelling has led to the development of the sentinel node biopsy technique.
Sentinel lymph node biopsy — Sentinel node biopsy is an alternative to complete removal of the axillary lymph nodes that has significantly fewer arm complications.
The concept is based on the premise that tumor cells from a breast tumor first involve one or a few lymph nodes before involving lymph nodes in other areas or spreading to distant organs. To identify this sentinel node, the surgeon injects blue dye, a radioactive material, or a combination of both into the area surrounding the tumor, where it enters lymphatic channels and then flows to lymph nodes.
If a SLN is identified, it is removed and examined under the microscope. If this node is does not contain any cancer cells, there is a very small chance that other axillary nodes will be positive and a full ALND is not necessary [11]. In contrast, if the SLN is positive, there is a good chance that other nodes will contain tumor cells, and a full ALND is usually performed.
The main problem with SLN biopsy is that a SLN may be "falsely" negative, meaning that the axillary lymph nodes actually contain tumor cells when the SLN predicts that they do not. The likelihood of a false-negative SLN is related to a surgeon's experience with this procedure. In experienced hands, the risk of a false positive is about 5 percent [12].
Guidelines from the American Society of Clinical Oncology support the use of SLN biopsy as an alternative to full ALND in many patients with early stage breast cancer as long as there is no suspicion from the physical examination that the axillary nodes may be involved with tumor spread [11].
RECURRENCE AFTER BCT — A local recurrence refers to a return of cancer in the breast tissue or the surrounding chest wall. After mastectomy, local recurrences are in the chest wall because there is no remaining breast tissue; following BCT, a recurrence is usually within the remaining breast tissue.
In women with stage I or II breast cancer, local recurrence develops in 7 to 20 percent of women treated with BCT, and in 4 to 14 percent of women treated with mastectomy. However, the time course of recurrence is different. A local recurrence is often delayed for many years in women treated with BCT, whereas a local recurrence usually occurs within three years in women treated with mastectomy.
It is important to note that BCT does not completely prevent new breast cancers from arising in the remaining breast tissue. In women treated with BCT, the risk of a new, unrelated tumor on the same side is about 1 percent per year (eg, 13 percent risk over 15 years following the procedure).
Surveillance — Women who have undergone BCT must continue to perform breast self-exams and undergo screening of both breasts with mammography. A summary of the American Society of Clinical Oncology's recommendations for surveillance after breast cancer treatment is provided in table 2 (show table 2).
Risk factors — The likelihood that breast cancer will recur locally after BCT is influenced by individual factors, tumor factors, and treatment factors.
Individual factors — A woman's age appears to influence the risk of a local recurrence after BCT. Women who are age 40 years or younger at the time of BCT are more likely than older women to have a local recurrence after BCT. Other studies suggest that younger women may also be more likely to have a local recurrence after mastectomy. Thus, young age should not be used as a factor in choosing one treatment over another, but instead should be used as an indicator of a higher risk of a local recurrence.
Tumor factors — The likelihood of a local recurrence after BCT is also influenced by two tumor-related factors: Residual cancer cells at the edge of the wound — The presence of residual cancer cells at the edge of the wound (called the resection margin) increases the likelihood of a local recurrence after BCT. In one study, the rate of local recurrence after BCT was 7 percent in women in whom no residual cells are found, compared to 18 percent in women in whom residual cancer cells were found [13]. Although the surgeon will try to remove all of these cells during surgery, residual cells are sometimes detected after surgery on more detailed microscopic examination. Presence of cancer cells within ducts — The presence of cancer cells within many ducts of the removed breast tissue, termed an extensive intraductal component, is useful for assessing the likelihood of a local recurrence. A local recurrence is more likely when cancer cells are present in many ducts within the tumor or within the normal breast tissue, if tumor cells remain at the margin of resection. Certain findings on mammograms taken before surgery often alert the surgeon to the presence of cancer cells in ducts. In such cases, particular care must be taken by the surgeon to make certain that no remaining tumor cells are present at the surgical margins.
Treatment factors — Three treatment factors influence the likelihood of a local recurrence after BCT: Extent of surgery — Local recurrence of breast cancer after BCT is less likely when a greater amount of breast tissue is removed during surgery. Radiation boost — A radiation boost refers to the delivery of an extra dose of radiation to the area of the breast where the tumor was located. Some, but not all studies suggest that a radiation boost slightly reduces the likelihood of a local recurrence of breast cancer, although this boost may slightly reduce the cosmetic results of BCT. Chemotherapy or hormone therapy — Chemotherapy and/or hormonal therapy are often recommended following surgery for localized breast cancer. The addition of these therapies to BCT further reduces the likelihood of a local recurrence, although not all women will need both of these therapies.
As an example, in one study of women with node-negative, ER-negative breast cancer, women were treated with chemotherapy or no chemotherapy after BCT [14]. Cancer recurred locally within eight years in 2.6 percent of the women treated with chemotherapy and in 13.4 percent of the women who were not treated with chemotherapy.
In a second study in women with node-negative, ER-positive breast cancer, women were treated with tamoxifen or a placebo after BCT [15]. Cancer recurred locally within ten years in 4.3 percent of the women treated with tamoxifen, and in 14.7 percent of the women who were treated a placebo.
Treatment — Many women who have a local recurrence can undergo a "salvage" mastectomy, and still have a chance to be cured from their cancer if there is no further spread.
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Cancer Institute
1-800-4-CANCER
(www.nci.nih.gov)
People Living With Cancer: The official patient information
website of the American Society of Clinical Oncology
(www.plwc.org/portal/site/PLWC)
National Comprehensive Cancer Network
(www.nccn.org/patients/patient_gls.asp)
American Cancer Society
1-800-ACS-2345
(www.cancer.org)
National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
Susan G. Komen Breast Cancer Foundation
(www.komen.org)
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Saslow, D, Boetes, C, Burke, W, et al. American Cancer Society guidelines for breast cancer screening with MRI as an adjunct to mammography. CA Cancer J Clin 2007; 57:75.
2. Lehman, CD, Gatsonis, C, Kuhl, CK, et al. MRI evaluation of the contralateral breast in women with recently diagnosed breast cancer. N Engl J Med 2007; 356:1295.
3. Yamauchi, H, Stearns, V, Hayes, DF. When is a tumor marker ready for prime time? A case study of c-erbB-2 as a predictive factor in breast cancer. J Clin Oncol 2001; 19:2334.
4. Clarke, M, Collins, R, Darby, S, et al. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005; 366:2087.
5. Fisher, B, Anderson, S, Bryant, J, et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med 2002; 347:1233.
6. Vinh-Hung, V, Verschraegen, C. Breast-conserving surgery with or without radiotherapy: pooled-analysis for risks of ipsilateral breast tumor recurrence and mortality. J Natl Cancer Inst 2004; 96:115.
7. Abner, AL, Recht, A, Vicini, FA, et al. Cosmetic results after surgery, chemotherapy, and radiation therapy for early breast cancer. Int J Radiat Oncol Biol Phys 1991; 21:331.
8. Erickson, VS, Pearson, ML, Ganz, PA, et al. Arm edema in breast cancer patients. J Natl Cancer Inst 2001; 93:96.
9. NIH Consensus Development Conference statement on the treatment of early-stage breast cancer. Oncology (Huntingt) 1991; 5:120.
10. Morrow, M, White, J, Moughan, J, et al. Factors predicting the use of breast-conserving therapy in stage I and II breast carcinoma. J Clin Oncol 2001; 19:2254.
11. Lyman, GH, Giuliano, AE, Somerfield, MR, et al. American Society of Clinical Oncology Guideline Recommendations for Sentinel Lymph Node Biopsy in Early-Stage Breast Cancer. J Clin Oncol 2005; 23:7703.
12. Guidelines from the American Society of Breast Surgeons available online at www.breastsurgeons.org/officialstmts/sentinel.shtml (accessed September 13, 2005).
13. Park, CC, Mitsumori, M, Nixon, A, et al. Outcome at 8 years after breast-conserving surgery and radiation therapy for invasive breast cancer: influence of margin status and systemic therapy on local recurrence. J Clin Oncol 2000; 18:1668.
14. Fisher, B, Dignam, J, Mamounas, EP, et al. Sequential methotrexate and fluorouracil for the treatment of node-negative breast cancer patients with estrogen receptor-negative tumors: eight-year results from National Surgical Adjuvant Breast and Bowel Project (NSABP) B-13 and first report of findings from NSABP B-19 comparing methotrexate and fluorouracil with conventional cyclophosphamide, methotrexate, and fluorouracil. J Clin Oncol 1996; 14:1982.
15. Fisher, B, Dignam, J, Bryant, J, et al. Five versus more than five years of tamoxifen therapy for breast cancer patients with negative lymph nodes and estrogen receptor-positive tumors. J Natl Cancer Inst 1996; 88:1529.
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