Zanmbeel

Friday, October 12, 2007

Screening for breast cancer

INTRODUCTION — Cancer screening refers to the use of tests to detect cancer at an early stage, before it causes symptoms and hopefully at a time when it is curable. More than 200,000 women in the United States are newly diagnosed with breast cancer each year. About 40,000 women die each year of breast cancer, making it second only to lung cancer in cancer deaths among women.

The death rate from breast cancer has declined about 20 percent over the past decade [1]. This is due, in part, to the ability of increased screening to find the disease at earlier stages when the chances of successful recovery are higher. In fact, there is more scientific evidence supporting the use of screening tests for breast cancer than for any other type of cancer.

The information presented here is for women at usual risk of breast cancer. Women with a known genetic mutation, like BRCA1 and BRCA2, or who have several close relatives with breast cancer should see "Patient information: Genetic testing for breast and ovarian cancer" for information about screening recommendations.

SCREENING METHODS — There are three main methods of screening for breast cancer: mammography, clinical breast examination, and breast self-examination.

Mammography — A mammogram is a breast x-ray that is the best screening test for reducing the risk of dying from breast cancer. Early concerns about the radiation exposure from mammograms have lessened with the use of modern mammography equipment that exposes the breast to extremely low levels of radiation. The current level of radiation exposure is unlikely to significantly increase the risk of developing breast cancer.

The cost of mammograms is covered by most private insurances, Medicare, and Medicaid. The American Cancer Society has information about low cost mammograms that are available in most communities (1-800-ACS-2345).

Technique — Before the mammogram, patients are asked to undress from the waist up and wear a hospital gown. Each breast is x-rayed individually. The breast is flattened between two panels, which allows the radiologist to more easily see abnormalities. This can be uncomfortable, though the discomfort lasts for only a few seconds. Mammograms are most uncomfortable when done just before or at the beginning of the menstrual period; women should try to avoid scheduling their mammogram at these times, if possible.

Findings — The mammogram is interpreted by a radiologist. Sometimes the radiologist is present at the time of the mammogram; in these cases, a patient may be asked to wait a few minutes while the radiologist determines if anything requires further evaluation. So, a woman may be asked to have additional x-rays. All mammography facilities are required to send results within 30 days; patients must be contacted within five days if the mammogram is abnormal.

Breast cancer cannot be diagnosed by mammography alone. Women usually require further testing (eg, ultrasound or biopsy) if the mammogram shows a mass, new calcium deposits, or other abnormal findings. These findings do not always mean that a cancer has been found. One study found that 11 percent of mammograms performed in the United States require additional evaluation; the area in question was not cancer in more than 90 percent of these cases [2].

The abnormalities that radiologists typically look for on mammograms are calcifications and masses (show figure 1 and show figure 2). Macrocalcifications are large calcium deposits that most often represent degenerative changes in the breast such as might occur with aging or with previous trauma or inflammation. Macrocalcifications are common, particularly in women over the age of 50, and generally do not require a biopsy. Microcalcifications are small specks of calcium that sometimes suggest the presence of breast cancer. Depending upon the shape and pattern of microcalcifications, the radiologist may recommend a biopsy of the affected area or a repeat mammogram in three to six months. Masses that appear on mammograms may represent cancer or a variety of benign disorders such as cysts or fibroadenomas. Ultrasound or needle aspiration is often recommended to determine if a mass is a cyst. If it is not a cyst, biopsy may be necessary.

Clinical breast examination — Clinical breast examination is the visual and manual examination of the breasts by a health care provider. Both clinical breast examination and mammography appear to be important; studies show that about 50 percent of breast cancers found on screening were detected by both examination and mammography. Five to 10 percent are detected with examination and missed by mammography, and about 40 percent are detected by mammography and missed by examination.

Clinical breast examination is typically performed at the yearly physical examination. Healthcare providers usually inspect the breasts for any changes in size or shape and then palpate (feel) the breasts and the area under both arms for any change in texture or the presence of lumps.

Breast self-examination — Breast self-examination is a means of detecting changes in your breasts. It typically is performed at the same time each month. For women who are menstruating, this may be about one week after the menstrual period ends, when the breasts are least lumpy. In postmenopausal women who are not menstruating, this may be on the same day each month.

Most studies have not found breast self-examination to be beneficial. One large randomized trial found breast self-examination did not reduce the risk of dying from breast cancer but did result in women undergoing more breast biopsies for benign lumps [3]. Nevertheless, some women feel that practicing breast self-examination regularly improves their ability to detect subtle changes that would otherwise not have been appreciated. Breast self-examination is not a substitute for mammography or clinical breast examination by a health care professional.

The studies that have been performed to date suggest that performing breast self-examination correctly is important. Patients who want to perform self-examinations should ask their health care provider to demonstrate how to do it and how to tell the difference between normal tissue and suspicious lumps.

Breast MRI — Magnetic resonance imaging (MRI) uses a strong magnet rather than x-rays or radiation to create a detailed image of a part of the body. Breast MRI may be recommended to aid in the diagnosis of breast cancer in selected situations (show radiograph 1) [4]. MRI is not recommended to detect breast cancer in women who do not have a high risk of breast cancer because of the increased risk of a falsely positive result (when the MRI shows a suspicious mass that is not cancer). In addition, MRI is not as good as mammogram in detecting certain breast conditions, such as ductal carcinoma in situ.

RECOMMENDATIONS — All major North American groups that make recommendations about breast cancer screening recommend routine screening with both mammography and clinical breast examination for women ages 50 years and older. There is controversy about routine screening among women in their 40s, although over time, more and more groups are recommending screening for women in their 40s as well. The American Cancer Society, American College of Radiology, American Medical Association, United States Preventive Services Task Force, and American College of Obstetrics and Gynecology all recommend starting routine screening at age 40 years. The US Preventive Services Task Force and American Academy of Family Physicians recommends screening mammography every one to two years for women ages 40 and older [5]. The American College of Physicians and The Canadian Task Force on the Periodic Health Examination recommend beginning routine screening at age 50 years. A 1997 National Institutes of Health Consensus Development Conference Panel Report on breast cancer screening in women ages 40 to 49 years recommended that women in this age group decide individually about breast cancer screening with their health care provider [6]. A 2007 guideline from the American College of Physicians makes a similar recommendation [7].

Defining routine screening — Most North American expert groups suggest that women over age 50 be screened every year. Groups that recommend screening for women in their 40s have tended to shift from recommending every one to two years to recommending every year because of the evidence of more rapid tumor growth in younger women.

There are no clear data on the effectiveness of routine screening mammography in women over age 70 years. Some researchers believe that mammography is less useful in these women because they have a reduced life expectancy and tumor growth is usually slower in older women. However, most expert groups recommend that because the risk for breast cancer increases as women age, routine screening should be continued as long as a woman has a life expectancy of at least 10 years. The recommended interval for women over the age of 70 is one to two years, depending upon a woman's individual risk of breast cancer. (See "Patient information: Risk factors for breast cancer").

The bottom line — All women should discuss mammograms with their clinician starting at age 40. Mammograms have the highest rate of detecting breast cancer. Virtually every well-performed study to date has found that screening mammography in women ages 50 and older reduces the risk of dying from breast cancer. A summary of trials found a 22 percent reduction in mortality in women in this age group who had regular mammography compared with women who did not [8]. For women in their 40s, the protection is somewhat less, both because breast cancer is less common and because it is harder to find with screening (examination and imaging tests) in younger women.

There are trade-offs between the benefits and risks of mammography in detecting: Breast cancers (that may end a woman's life prematurely) Precancerous lesions such as ductal carcinoma in situ (DCIS) (that often do not progress) False-positive results (that cause anxiety and potentially require unnecessary testing)

All women, especially those in their 40s, should discuss their situation with a health care provider and decide together when to start screening. Some useful information when considering mammography screening is presented in the figures (show figure 3A-3B). This figure shows what happens when 1000 women ages 40, 50, or 60 get annual mammograms for 10 years. It is possible to compare the number of women saved from death from breast cancer with the number of false-positive mammograms or diagnosis with DCIS.

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)
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. Chu, KC, Tarone, RE, Kessler, LG, et al. Recent trends in U.S. breast cancer incidence, survival, and mortality rates. J Natl Cancer Inst 1996; 88:1571.
2. Brown, ML, Houn, F, Sickles, EA, et al. Screening mammography in community practice: positive predictive value of abnormal findings and yield of follow-up procedures. AJR Am J Roentgenol 1995; 165:1373.
3. Thomas, DB, Gao, DL, Ray, RM, et al. Randomized trial of breast self-examination in shanghai: final results. J Natl Cancer Inst 2002; 94:1445.
4. 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.
5. U.S. Preventive Services Task Force. Guide to Clinical Preventive Services, Third Edition. www.ahrq.gov/clinic/uspstfix.htm (Accessed 3/7/05).
6. National Institutes of Health Consensus Development Conference Statement Jan 21-23,1997. 103. Breast cancer screening for women ages 40-49. consensus.nih.gov/cons/103/103_intro.htm (Accessed October 26, 2005).
7. Qaseem, A, Snow, V, Sherif, K, et al. Screening mammography for women 40 to 49 years of age: a clinical practice guideline from the American College of Physicians. Ann Intern Med 2007; 146:511.
8. Humphrey, LL, Helfand, M, Chan, BK, Woolf, SH. Breast cancer screening: A summary of the evidence for the US Preventive Services Task Force. Ann Intern Med 2002; 137:347.

Screening for breast cancer

Risk factors for breast cancer

INTRODUCTION — About 200,000 women in the United States are diagnosed with breast cancer each year. However, not all women have the same risk of developing breast cancer during their lifetime. Studies have shown that certain factors, called risk factors, increase the likelihood that a woman will develop breast cancer (show table 1). Many of these risk factors are not reversible, but some can be modified.

Not all factors increase a woman's chance of developing breast cancer equally. Some factors (such as inheriting a breast cancer-related gene) increase a woman's risk of breast cancer more than others (see "Strong risk factors" below).

The presence of breast cancer risk factors does not mean that cancer is inevitable: many women with risk factors never develop breast cancer. Instead, risk factors help to identify women who may benefit most from screening or other preventive measures. Individual women should work with their clinicians to determine their own personal risk of breast cancer. based upon their own circumstances.

It is important to remember that breast cancer can also occur in women who have no identifiable risk factors. The average woman has about a 10 to 15 percent chance of developing breast cancer if she lives into her 90s. On the other hand, the risk of developing breast cancer in a woman with a strong family history of the disease who has inherited one of the genes that predispose her to breast cancer is over 50 percent. All women should discuss guidelines for breast cancer screening with their clinicians, even if they have a low risk for breast cancer based upon their risk factor profile.

This topic review discusses the individual factors that increase a woman's risk of developing breast cancer, and also reviews those factors that are thought to protect against the development of breast cancer.

STRONG RISK FACTORS — Unlike lung cancer, for which smoking is the biggest and most powerful risk factor, there is no single factor that is responsible for the majority of breast cancers in women. Nevertheless, there are three factors which strongly increase a woman's risk of developing this disease: advancing age, family history of the disease, and a personal history of breast cancer (show table 1).

Increasing age — The primary risk factor for breast cancer in most women is older age (show table 2). Overall, 85 percent of cases occur in women 50 years of age and older, while only 5 percent of breast cancers develop in women younger than age 40. Most North American expert groups suggest that women over age 50 be screened for breast cancer every year. Although the benefit of breast cancer screening of women in their 40s is controversial, most groups also recommend yearly screening; others recommend screening only every other year in women of this age group. Women over the age of 70 may choose to have mammography every other year because tumor growth is typically slower in older women. (See "Patient information: Screening for breast cancer").

Family history — Women who have a family history of breast or ovarian cancer are at a higher risk for breast cancer than those who lack such a history (show table 3). Women who have an especially strong family history (eg, two or more first-degree relatives [a mother, daughter, or sister] with breast or ovarian cancer, particularly before menopause), have a greater than 50 percent chance of developing breast cancer. This represents an approximately five to 10-fold increase in a woman's baseline risk of developing breast cancer (show table 3).

One of the main factors responsible for this elevated risk has been identified: an inherited genetic mutation in one of two genes, called BRCA1 and BRCA2. Although women who inherit these mutations have a particularly high lifetime risk of breast cancer, only about 1 in 1000 women have a BRCA mutation, and BRCA1 and 2 mutations are responsible for only about 5 percent of all breast cancers. Women of certain ethnic backgrounds (in particular Ashkenazi Jewish women of Eastern European descent) are at a higher risk of inheriting BRCA mutations than are women of other ethnic backgrounds. About 2 percent (2 in every 100 women) have inherited a BRCA mutation, and between 12 and 30 percent of breast cancers in this group are thought to be caused by BRCA mutations.

It is possible to test for the presence of mutations in these genes in families who are at high risk of having them. Family history as a risk factor for breast cancer and genetic testing for the BRCA mutations is discussed in detail elsewhere. (See "Patient information: Genetic testing for breast and ovarian cancer").

Previous breast cancer — Women who have had cancer in one breast have an increased risk of developing cancer in the other breast. This is especially true if a woman has an inherited BRCA mutation. This fact underscores the need for close surveillance after treatment of a breast cancer, particularly in a woman who has inherited a BRCA mutation.

MODERATE RISK FACTORS — Five factors can modestly increase a woman's risk of developing breast cancer (with the presence of each factor increasing the relative risk by 1.5 to 2-fold) (show table 1):

Density of the breasts on mammogram — Women whose mammograms show many dense areas of tissue have an increased risk of breast cancer compared to women whose mammograms reveal mainly fat tissue. A woman who is told that her mammogram has areas of increased density should ask her healthcare provider to explain what this means.

Biopsy abnormalities — Women who have had a prior breast biopsy that revealed a proliferative abnormality (excessive growth of the glandular breast tissue, also called hyperplasia) have an increased risk for breast cancer, particularly if the cells appear abnormal (atypical hyperplasia, show figure 1). Otherwise, benign breast conditions that are not proliferative (eg, fibrocystic change, or a noncomplex fibroadenoma) do not increase the risk of a woman developing breast cancer. Any woman who undergoes a biopsy of a breast abnormality needs to fully understand the results, particularly if they impact the frequency of breast cancer screening.

Exposure to radiation — Women who have undergone high-dose radiation therapy to the chest region, usually as part of cancer treatment, have an increased risk for breast cancer compared to women who have never had radiation therapy.

OTHER RISK FACTORS — Several other factors can increase a woman's risk of developing breast cancer. Many of these factors are related to exposure to a hormone, estrogen. None are very powerful risk factors.

Age at time of reproductive events — During a woman's reproductive years, estrogen stimulates cells of the breast's glandular tissue to divide. The longer a woman is exposed to estrogen, the greater her risk for breast cancer. Estrogen exposure is increased if a woman began menstruating at or before 11 years of age, or if she experiences menopause at age 55 years or older.

Pregnancy and breastfeeding — Women who have never given birth are more likely to develop breast cancer after menopause than women who have given birth multiple times. The timing of a first pregnancy also appears to play a role; women who have their first full-term pregnancy at the age of 30 years or older have an increased risk of breast cancer as compared to women who give birth before age 30.

Hormone replacement therapy (HRT) — As a woman ages, the breast's glandular tissue, the tissue in which breast cancer arises, is gradually replaced by fat. HRT includes estrogen, which slows or reverses this process. A large clinical trial has found that long-term use of combined estrogen-progestin (approximately five years) in women ages 50 to 79 increases a woman's risk of breast cancer, as well as heart disease, stroke, and clots in the legs (show figure 2). The risk of breast cancer when estrogen is used alone does not appear to be increased, especially when used for a short time. (See "Patient information: Postmenopausal hormone therapy and breast cancer").

Each woman should discuss the pros and cons of this therapy with her clinician before deciding if it is right for her. Alternatives to estrogen therapy may be preferable for some women, while others may choose to use estrogen for some period of time.

Height and weight — Tall women are more likely than short women to develop breast cancer. Weight also plays a role, possibly because body fat alters a woman's estrogen metabolism. Obese women are more likely than thin women to develop breast cancer after menopause (show table 1).

Alcohol consumption — Women who consume alcohol have an increased risk of breast cancer, perhaps due to elevated levels of estrogen in the body (show table 1). The more alcohol a woman drinks, the greater her risk. However, moderate alcohol intake may protect against other diseases. There is evidence that women can protect themselves against the alcohol-breast cancer link by consuming an adequate amount of folic acid with a daily multivitamin and by eating leafy green vegetables. Women should discuss the benefits and risks of alcohol consumption with their healthcare provider. (See "Patient information: Risks and benefits of alcohol consumption").

Presence of other cancers — Women who have been diagnosed with cancer of the endometrium, ovary, or colon are more likely to develop breast cancer than women who do not have these cancers.

Miscellaneous factors — Several other factors are linked to breast cancer risk for reasons that are unknown. Women of high socioeconomic status are more likely than women of low socioeconomic status to develop breast cancer, and women who live in urban settings are more likely than women who live in rural settings to develop breast cancer. Some studies support an association between exposure to light at night (such as with night shift work) and the risk of breast cancer, but the strength of the association has been variable (show table 1).

Race/ethnicity and religion also appear to play a role in breast cancer risk. Black women are more likely than Asian women to develop breast cancer before the age of 40 years, whereas White (non-Hispanic) women are more likely than Asian women to develop breast cancer at the age of 40 years and older. Women of Ashkenazi (Eastern European) Jewish heritage are more likely to develop breast cancer because they are more likely to carry a genetic mutation associated with breast cancer (BRCA1 or BRCA2). Women who smoke also appear to have an increased risk of breast cancer.

There are some factors that have no impact or an unknown impact on the risk of breast cancer (show table 4)

DECREASING THE RISK — Several factors can decrease the risk of breast cancer (show table 5).

Removal of the ovaries — Most women retain their ovaries throughout their reproductive years, but certain conditions may necessitate surgical removal of the ovaries at a very young age. Women whose ovaries have been removed before age 35 are at lower risk of breast cancer later in life than whose ovaries have not been removed. However, removal of the ovaries places women at higher risk for more common diseases such as coronary heart disease and osteoporosis, and oophorectomy is not recommended for breast cancer prevention in most women (show table 6); women with the BRCA1 or BRCA2 gene mutation may be encouraged to have their ovaries removed (See "Patient information: Genetic testing for breast and ovarian cancer").

Lifestyle changes — A number of lifestyle changes may reduce breast cancer risk: Minimize the use of postmenopausal hormones. Consider non-estrogenic alternatives (eg, bisphophonates for treatment of osteoporosis rather than hormones, see "Patient information: Osteoporosis prevention and treatment" and see "Patient information: Alternatives to postmenopausal hormone therapy"). Although this may not necessarily be a lifestyle choice, having a first child at an earlier age may decrease risk Breast feeding for at least six months may decrease breast cancer risk. Avoiding adult weight gain and maintaining a healthy weight may reduce postmenopausal breast cancer risk. Limiting alcohol consumption may also reduce risk. For those who drink, adding the vitamin folic acid to the diet may reduce this increased risk. Regular physical activity may also decrease risk.

Medication — For women who are already at higher than average risk, their risk of developing breast cancer can be reduced by at least 50 percent or more by taking tamoxifen or raloxifene for five years. Tamoxifen is the only drug approved by the United States Food and Drug Administration (FDA) for the prevention of breast cancer.

The common side effects of tamoxifen are not serious (eg, hot flashes, menstrual irregularities, vaginal discharge), but the uncommon ones (eg, blood clots, pulmonary embolus, stroke and uterine cancer) can be life threatening and are predominantly seen in women over 50 years of age.

Raloxifene is associated with a lower risk of thromboembolic events, and probably uterine cancer as well, but is not yet approved as a chemopreventive agent. These topics are discussed in detail elsewhere. (See "Patient information: Tamoxifen and raloxifene for the prevention of breast cancer").

Early detection — Even if breast cancer incidence cannot be substantially reduced for some women who are at high risk for developing the disease, the risk of death from breast cancer can be reduced with regular mammography screening. (See "Patient information: Screening for breast cancer").

ESTIMATING RISK — Many factors can affect a woman's risk for breast cancer. The relative importance of each of these factors can be confusing.

In most cases, a woman and her clinician can use a scoring system from the National Cancer Institute to estimate personal risk. Calculation of the score entails multiplying a woman's baseline risk (based upon her age and race/ethnicity) and the risks associated with five key factors. The individual's risk is compared with a woman the same age who has an "average risk" of developing breast cancer. The tool is available from the NCI by calling 1-800-4CANCER or on their web site at www.cancer.gov/bcrisktool/.

Another useful source for estimating personal risk of breast cancer is the Harvard Center for Cancer Prevention Web site, "Your Disease Risk" (at www.yourdiseaserisk.harvard.edu). After answering a few questions about age, history of cancer, height, weight, reproductive history, medical history and family history, a calculation is made of breast-cancer risk.

A healthcare provider can explain what the numbers actually mean, discuss guidelines for screening based upon personal risk, and possibly recommend steps for reducing the risk of breast cancer.

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)

[1-5]

Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Hulka, BS, Stark, AT. Breast cancer: Cause and prevention. Lancet 1995; 346:883.
2. Olsen, O, Gotzsche, PC. Cochrane review on screening for breast cancer with mammography. Lancet 2001; 358:1340.
3. Freedman, DA, Petitti, DB, Robins, JM. On the efficacy of screening for breast cancer. Int J Epidemiol 2004; 33:43.
4. National Cancer Institute. Breast Cancer (PDQ®): Screening. Available at: cancer.gov/cancertopics/pdq/screening/breast/healthprofessional (Accessed November 21, 2005).
5. Kosters, JP, Gotzsche, PC. Regular self-examination or clinical examination for early detection of breast cancer. Cochrane Database Syst Rev 2003; :CD003373.

Risk factors for breast cancer

Postmenopausal hormone therapy and breast cancer

INTRODUCTION — Hormone replacement therapy (HRT) refers to the use of hormones, including estrogen and progesterone, during and after the menopause. Estrogen levels fall at the time of menopause, producing well-known symptoms such as hot flashes and vaginal dryness. In addition, lower levels of estrogen are believed to increase a woman's risk for both bone thinning (osteoporosis) and heart disease after menopause. Many women use estrogen and progestin replacement to relieve bothersome symptoms of menopause.

This topic review provides information about the link between hormone replacement and breast cancer. Detailed discussions of the risks and benefits of HRT, available preparations, recommendations for who should or should not take estrogen, and alternatives to estrogen are found elsewhere. (See "Patient information: Postmenopausal hormone therapy" and see "Patient information: Alternatives to postmenopausal hormone therapy").

ESTROGEN AND BREAST CANCER — Estrogen is produced by the ovaries, although the amount of estrogen that is produced varies over a lifetime. Evidence from numerous studies indicate that exposure to naturally occurring estrogen can affect a woman's risk of breast cancer. The risk appears to increase with prolonged exposure (for women who have their first menstrual periods at an early age or menopause at a late age). The risk may also increase if she is exposed to high levels of estrogen. A full discussion of risk factors for breast cancer is available separately. (See "Patient information: Risk factors for breast cancer").

HRT AND BREAST CANCER — Estrogen and progesterone can stimulate breast cells to proliferate (grow and multiply). Proliferating cells are more likely to develop the genetic damage that leads to breast cancer. Furthermore, estrogen and progesterone can stimulate the growth of breast cancers that have already developed. Therefore, one of the main concerns for women thinking about taking HRT is the risk of developing breast cancer.

The best information about HRT and the risk of breast cancer is from the Women's Health Initiative (WHI), a large clinical trial comparing the risk of breast cancer in women who took HRT versus women who took a placebo (sugar pill). The WHI also examined the risk of other conditions, such as heart disease, bone thinning, and colon cancer. Women who did not have a uterus (eg, after hysterectomy) were randomly assigned to receive estrogen (Premarin) or placebo; women with a uterus received combined estrogen-progestin (Prempro) or placebo.

Estrogen plus progestin — Researchers expected to see a decreased risk of heart disease and a slightly increased risk of breast cancer in women who took hormones. Instead, they found that women who took combined estrogen-progestin had an increased risk of breast cancer and cardiovascular complications (heart attacks, strokes, blood clots). There were 38 cases of breast cancer per 10,000 women/year taking hormones versus 30 per 10,000 women taking placebo (sugar pills). This means that 8 additional women per year per 10,000 women developed breast cancer because of their use of estrogen-progestin. Similar findings have been noted in a number of other studies.

For these reasons, the estrogen plus progestin part of the trial was stopped in July 2002. Although there are other benefits of HRT (lower risk of osteoporotic fracture and colon cancer), the overall risks outweigh the benefits for many women if HRT is taken long-term. HRT is an effective short-term treatment for the relief of menopausal symptoms, but is no longer recommended long-term treatment (greater than five years).

One criticism of the WHI was that the average age of women who enrolled was 63 years. Thus, the results of the study may be different for peri- and newly postmenopausal women, who are typically 10 to 15 years younger. Therefore, the risks of HRT may be less concerning for women in their 50's compared to women in their 60's, especially if HRT is taken for less than five years.

Effects of progestins — There is good evidence that use of estrogen and a progestin increases the risk of breast cancer more than if estrogen is used alone. However, women who have a uterus should not take estrogen alone because of the increased risk of developing endometrial hyperplasia or uterine cancer; these conditions can develop after as little as six months of estrogen alone. Thus, women who have a uterus must take a progestin if estrogen is taken. For women who have had a hysterectomy, estrogen alone is preferred.

Estrogen alone — The results of the WHI trial of unopposed estrogen were different than those of combination estrogen and progestin: it showed an increased risk of stroke and blood clots, but no increase in breast cancer or heart attack risk. (See "Patient information: Postmenopausal hormone therapy").

Duration of use — All of these studies suggest that the major increase in breast cancer risk occurs after a woman has used estrogen-progestin for four to five years. Again, in the WHI, there was no increased risk of breast cancer in the women who took only estrogen.

Effects of past use — The risk of breast cancer associated with HRT decreases after a woman stops using HRT, even if she has taken HRT for a long time. In one study, the risk of breast cancer in women who had stopped using HRT more than five years ago was the same as the risk in women who had never been on HRT. Ongoing studies will help clarify the long-term effects of past HRT use on breast cancer risk.

Other factors that increase risk of breast cancer

Alcohol — Postmenopausal women on HRT who also drink alcohol (more than 1.5 to 2 drinks per day) appear to be at greater risk of breast cancer than HRT users who do not drink alcohol.

Family history of breast cancer — Some studies suggest that HRT further increases the risk of breast cancer in women who have a family history of this cancer. However, other studies have found that HRT does not increase the risk of breast cancer in women with a family history of breast cancer any more than in women without a family history of this cancer.

Personal history of breast cancer — Many women are now surviving for long periods of time after the diagnosis of a breast cancer because of earlier detection and improvements in treatment. As these women age, they are facing menopause (sometimes as a result of treatment-induced early menopause) and other health conditions such as osteoporosis.

The effects of HRT on the risk of a recurrence of breast cancer have been uncertain. However, in the HABITS trial, women with breast cancer who received HRT were at increased risk for a breast cancer recurrence.

Therefore, we do not recommend using estrogen or estrogen plus progestin in women with a personal history of breast cancer. Instead, alternatives to HRT should be tried. (See "Patient information: Alternatives to postmenopausal hormone therapy").

It was previously thought that women who developed breast cancer while taking HRT had a better chance of cure compared to women with breast cancer who were not taking HRT. Based upon the results of the WHI, this does not appear to be true.

SCREENING FOR BREAST CANCER — Regular breast cancer screening is essential for all women, especially those who decide to use HRT. Screening includes a combination of breast self-exams, annual breast exams with a healthcare provider, and an annual mammogram. (See "Patient information: Screening for breast cancer").

WHEN TO USE HORMONE REPLACEMENT THERAPY — Data from the Women's Health Initiative, as well as other trials, have led to changes in the recommendations for estrogen therapy [1,2]. Continuous estrogen-progestin therapy appears to increase the risks of cardiovascular events and breast cancer in women over age 60. Medications other than hormones are available to prevent and treat osteoporosis. As a result, long-term hormone replacement therapy to prevent heart disease or osteoporosis is not recommended. Most experts recommend avoiding hormone replacement therapy or using it for the shortest possible duration to control menopausal symptoms.

However, hormone replacement therapy is the most effective treatment for relief of menopausal symptoms. HRT is a reasonable option for most peri- or postmenopausal women, with the exception of those with a history of breast cancer, heart disease, a previous blood clot or stroke, or those at high risk for these complications. In otherwise healthy women, the risk of these complications is small.

In women being treated with HRT for symptoms, the goal is to eventually taper and stop the hormones (unless there is a compelling reason, such as quality of life, to continue it long-term). After the planned treatment interval, the hormones should be discontinued gradually, for example, by omitting one pill per week, to minimize recurrence of the menopausal symptoms.

After stopping HRT, there are several alternatives to HRT for treatment of menopausal symptoms and prevention of osteoporosis. (See "Patient information: Alternatives to postmenopausal hormone therapy").

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)
The Hormone Foundation

(www.hormone.org/public/menopause.cfm, available in English and Spanish)

[1-3]

Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Clemons, M, Goss, P. Mechanisms of disease: estrogen and the risk of breast cancer. N Engl J Med 2001; 344:276.
2. Rossouw, JE, Anderson, GL, Prentice, RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA 2002; 288:321.
3. Rutter, CM, Mandelson, MT, Laya, MB, Taplin, S. Changes in breast density associated with initiation, discontinuation, and continuing use of hormone replacement therapy. JAMA 2001; 285:171.

Lymphedema after breast cancer surgery

INTRODUCTION — Lymphedema is one of the most troubling complications after breast cancer surgery (specifically after axillary lymph node surgery). It is caused by interruption of the lymph drainage in the axilla, which produces swelling of the arm, discomfort and an abnormal appearance of the arm. Many women find that lymphedema can worsen the physical and emotional strain of dealing with breast cancer.

The overall incidence of lymphedema after treatment for breast cancer is 25 percent, although this varies depending upon the extent of surgery, the time since surgery, and whether radiation therapy was used. Generally, patients who undergo more extensive surgery, have many lymph nodes removed, or have radiation therapy to the axilla after surgery are more likely to develop lymphedema. Most women who develop lymphedema do so within four years after their operation.

CAUSES — Lymph is a clear fluid that contains mostly white blood cells (the blood cells that fight infection). The lymphatic system drains the body's tissues and organs into a series of tubes or ducts. The fluid is filtered through lymph nodes (also called glands) and eventually drains into the blood stream.

Lymphedema that develops after treatment for breast cancer is called secondary lymphedema. It develops because there is a disruption in the normal lymphatic drainage. This interruption can be caused by: Surgery, particularly removal of the lymph glands in the armpit (also called the axilla) Trauma or injury to the arm Infection caused by insect bites or scratches after breast cancer surgery Tumor-related obstruction of the lymph drainage Radiation treatment to the axilla

As expected, women who require axillary lymph node dissection because of a positive sentinel lymph node have more arm symptoms than those who undergo only sentinel lymph node biopsy. In one trial that compared women who underwent sentinel lymph node biopsy alone versus women who had sentinel lymph node biopsy followed by axillary lymph node dissection, the sentinel lymph node biopsy alone group had lower rates of arm edema (4 versus 19 percent), impaired shoulder range of motion (4 versus 11 percent), shoulder/arm pain (8 versus 21 percent), and numbness (11 versus 38 percent) [1].

Patients who develop lymphedema many years after surgery, or who have lymphedema that is increasing, should be evaluated for a possible recurrence of the breast cancer.

SYMPTOMS — Initially, patients may experience a heavy sensation in the affected limb, accompanied by an aching discomfort. The swelling may be soft and pitting at first. Typically this swelling becomes firm and nonpitting, and the skin becomes dry. Patients may have restricted movement, numbness, or a sense of stiffness in the arm.

Lymphedema has a different appearance than other types of edema. Edema caused by excessive fluid usually develops in the legs, and is caused by conditions such as cirrhosis or congestive heart failure. Edema causes pitting, which leaves an imprint for several seconds when a finger is pressed into the swelling. In contrast, lymphedema is non-pitting. (See "Patient information: Edema").

IMPACT OF LYMPHEDEMA — While lymphedema is not a life-threatening condition, it can have a major impact on a person's lifestyle and quality of life. A change in cosmetic appearance often leads to concerns about body image.

After breast cancer surgery, many women are already self-conscious about their appearance, and the edema can worsen this concern. Psychologic symptoms such as anxiety, depression, social avoidance, and sexual dysfunction can result. A decreased ability to use the affected arm can impact quality of life, particularly if it is the patient's dominant arm. Lymphedema can reduce tissue healing and occasionally causes chronic pain. For these reasons, prevention strategies and early treatment of lymphedema are strongly recommended.

PREVENTION STRATEGIES — A number of recommendations for the prevention of lymphedema have been proposed, although the effectiveness of those recommendations is variable. Early identification and treatment can help to minimize the severity of lymphedema. Patients should report any symptoms of pain or swelling to a healthcare provider as soon as possible; do not wait for symptoms to worsen.

Some possible preventive strategies include: Avoid trauma and injury to the affected arm. Injections should not be done in the affected arm, if at all possible. Blood drawing and placement of intravenous lines may occur but caution is needed to minimize pressue and avoid infection. Avoid constriction in the affected arm. Tight fitting clothing, blood pressure monitoring or any activity that could interfere with lymph flow should be avoided. Try to prevent infection. Practice careful skin and nail hygiene to prevent an entry point for infection. Use skin moisturizes to prevent dry, cracked skin. Use topical antibiotics on small skin breaks or abrasions, such as a paper cut. Avoid heavy exercise and lifting heavy objects with the affected arm immediately after surgery. Moderate to heavy exercise of the limb may increase blood flow, which can increase edema. Check with a healthcare provider before resuming exercise or heavy activities. Gentle stretching and range of motion exercises, provided by the surgeon, may be used immediately after surgery. Avoid extreme temperature changes during bathing or washing dishes. Hot tubs and saunas should be avoided or used with caution. Avoid resting the arm below the heart or sleeping on the arm for prolonged periods Contact a healthcare provider if the affected arm develops a rash, becomes red, blistered, or warm, or if a fever develops (temperature greater than 100.4ºF or 38ºC). These symptoms could signal the beginning or worsening of lymphedema.

MONITORING — In a woman with lymphedema, the size of the arm is often monitored over time to detect changes and measure response to treatment. The standard way to estimate size is by taking measurements of the circumference of the arm at several pre-determined points.

An alternate way to measure is by using the water displacement method. This appears to be more accurate and sensitive to small changes in arm size, and is often used for clinical trials. However, it is not clear if there is any advantage of monitoring arm size at home by this more complicated method, as compared to a simple measurement of arm circumference.

A water displacement arm volumeter device has been developed for home use (show figure 1) [2]. The device can be made at home using widely available polyvinyl chloride (PVC) pipes that are sold in hardware stores. Instructions for building the home volumeter, as well as the appropriate technique for using the device, are provided by the author (show table 1).

TREATMENT — The underlying cause of lymphedema cannot be corrected. The main goals of treatment are optimizing preventive strategies to limit the amount of edema, provide symptom relief and prevent worsening of edema. Because drugs and surgery have shown little benefit and can sometimes be harmful, the main therapeutic approaches are non-surgical and nonpharmacologic (non-drug).

Treatment should encompass the range of symptoms a woman is experiencing. Eliminating discomfort, improving range of motion in the arm, and decreasing psychologic distress are important outcomes of therapy. Patients are often referred to clinicians or programs with expertise in treating lymphedema.

General measures — Careful skin and nail care should be performed to prevent infection, which may result in cellulitis and worsening of lymphedema. Women should avoid cuts, pinpricks, hangnails, insect bites, contact allergens or irritants, pet scratches, and burns to the affected arm. Patients should be encouraged to use skin moisturizers and topical antibiotic ointments after small breaks in the skin that occur as a result of a paper cut or abrasion. Protective gloves for household work and gardening also may be helpful. Use an electric razor rather than a razor blade to remove hair in the axilla.

Whenever possible, patients should avoid medical procedures, such as vaccination, blood pressure monitoring, acupuncture, and venography in the affected arm. (See "Prevention strategies" above).

Lymphedema may be worsened by saunas, steam baths, or hot tubs; spending time in hot climates; or travel. Many patients report worsening of their lymphedema during air flight, suggesting that patients who use compression sleeves should probably wear them in flight.

Patients are encouraged to maintain an ideal body weight. Obesity is a contributory factor for the development of lymphedema, and may limit the effectiveness of compression pumps or sleeves.

Nonpharmacologic therapy — Several nonpharmacologic treatment modalities are effective.

Arm elevation — Although elevation of the arm is not an effective treatment by itself, it may be recommended in conjunction with other therapies [3].

Exercise — After the immediate recovery phase, moderate exercise is recommended. If the arm starts to hurt, a patient should lie down and elevate the arm. Nonfatiguing exercises can enhance muscle contraction, which can improve lymph flow and reduce swelling. Walking, swimming, light aerobics, bike riding, and yoga are all recommended. Avoid repetitive movements against resistance with the affected arm, such as scrubbing or pushing/pulling heavy objects.

Some clinicians recommend avoiding certain forms of exercise, including rowing, tennis, golf, skiing, squash, racquetball, or other vigorous repetitive movements. However, there is no published evidence to suggest that these activities promote or worsen lymphedema.

Compression garments — Applying pressure to the arm can encourage fluid movement and ultimately reduce swelling. Compression can be achieved by using an elastic lymphedema sleeve (show picture 1A-1B), or by wrapping the arm in elastic bandages (if a sleeve does not fit). Some people require a custom-made garment if a standard size sleeve does not fit.

Use of a lymphedema sleeve is preferred to bandaging because it provides increased pressure at the wrist, which gradually lessens towards the axilla; this helps to move fluid better than bandages, which have equal pressure at all points along the arm. Whichever method is used, proper fit is important to avoid worsening edema in any one area of the arm. People who have lymphedema should wear a compression sleeve when flying.

Massage therapy — Another method to mobilize lymph fluid is massage or manual lymphedema therapy (MLT). MLT applies light pressure to the arm and torso to mobilize edema fluid from the fingers and hand to the upper arm and chest. It is thought that MLT of the skin and subcutaneous tissue may help open gaps or collateral channels between lymphatic ducts, enhancing the flow of fluid through the lymphatic system.

Massage is usually used in conjunction with compression garments and therapeutic exercise. Whenever possible, patients should be referred to practitioners trained in MLT. Patients and family members can also be trained in massage techniques, allowing the patient to continue therapy after finishing formal treatment with a therapist. Mild lymphedema may resolve in two to three weeks, but more severe cases will require a longer time. Patients with active infection or inflammation (redness) of the affected limb, a blood clot, active cancer, or congestive heart failure may not be good candidates for massage therapy.

Complex physical therapy — This is a multimodality approach that uses massage, skin care, exercise and compression garments. It is considered an effective treatment for lymphedema that is unresponsive to compression therapy alone.

External pneumatic compression — When patients do not respond to massage or pressure garments, external pneumatic compression may be used. This treatment uses a sleeve that is intermittently inflated, beginning at the lower end of the arm and working up towards the shoulder.

Currently, pneumatic compression is recommended only for patients treated in a formal lymphedema treatment program who have not improved with other therapies (massage, compression garments, exercise).

Drug treatment — Drug therapy is usually ineffective and, in some cases, can be harmful. Diuretics — Diuretics eliminate excess fluid from the body. Although they are often used to treat edema that develops in individuals with heart failure, they are not effective for lymphedema. Antibiotics — Antibiotics are used to treat infection. Antibiotic treatment should be discontinued after an infection has resolved; continued or preventive antibiotic therapy does not improve lymphedema. However, oral antibiotics may rarely be recommended for extended periods of time (ie, preventively) in patients who have chronic or recurrent infections.

Surgery — Surgery is rarely performed for the treatment of lymphedema following mastectomy. If indicated, the primary surgical approach is to remove subcutaneous fat and fibrous tissue with liposuction. The effectiveness of this approach has not been studied, and there is concern that lymphedema will eventually return following surgery.

Some specialized centers have performed lymphatic microsurgery that involves draining lymph fluid into the venous circulation. A newer technique, microsurgical lymph node transplantation, is under study.

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)
National Lymphedema Network

(www.lymphnet.org)

[3-5]

Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Langer, I, Guller, U, Berclaz, G, et al. Morbidity of Sentinel Lymph Node Biopsy (SLN) Alone Versus SLN and Completion Axillary Lymph Node Dissection After Breast Cancer Surgery: A Prospective Swiss Multicenter Study on 659 Patients. Ann Surg 2007; 245:452.
2. Lette, J. A simple and innovative device to measure arm volume at home for patients with lymphedema after breast cancer. J Clin Oncol 2006; 24:5434.
3. Brennan, MJ, Miller, LT. Overview of treatment options and review of the current role and use of compression garments, intermittent pumps, and exercise in the management of lymphedema. Cancer 1998; 83:2821.
4. Bertelli, G, Venturini, M, Forno, G, et al. An analysis of prognostic factors in response to conservative treatment of postmastectomy lymphedema. Surg Gynecol Obstet 1992; 175:455.
5. Rockson, SIG, Miller, LT, Senie, R, et al. American Cancer Society Lymphedema Workshop. Workgroup III: Diagnosis and management of lymphedema. Cancer 1998; 83:2882.

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Friday, October 12, 2007