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)


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