Risk Factors
Experts estimate that about 211,240 new cases of invasive female breast cancer will be diagnosed in the United States in 2005. About 1,690 breast cancer cases will be diagnosed in men during the year. Although breast cancer in men is rare, the incidence has been increasing, and men are diagnosed at a later stage than women. An estimated 40,410 women and 460 men will die from breast cancer in 2005. The earlier breast cancer is diagnosed, the earlier the opportunity for treatment. According to the American Cancer Society, over 2 million women who have been treated for breast cancer are alive today.
Age is a major identifiable risk factor. More than 80% of breast cancer cases occur in women over age 50. The odds by age are as follows:
- Cancer in women younger than 30 is very rare, accounting for only 1.5% of all breast cancer cases.
- At age 40, a woman's chances for breast cancer are 1 in 217.
- At age 50, they are 1 in 50.
- If a woman lives to be 85, the odds of her having breast cancer are 1 in 8.
Ethnicity and Race
Breast cancer is more prevalent among Jewish women of Eastern European (Ashkenazi) descent. In terms of race, African-American women tend to get breast cancer at an earlier age than Caucasians. Although African-American women have lower overall rates of breast cancer, they represent the highest proportion of women who are diagnosed with the disease before age 45 years. Comparative studies of breast cancer rates among sub-Saharan Africans suggest a genetic component, as African women are diagnosed most frequently between age 35 and 45 years.
The mortality rate in African-Americans is twice that of Caucasians, although it is declining. Social and economic factors make it less likely that African American women will be screened, so they are more likely to be diagnosed at a later stage. They are also less likely to have access to effective treatments. When they do have equal treatment, outcomes are the same as in Caucasian patients.
Inherited Genetic Factors and Family History
An estimated 10% of all women with breast cancer have a very strong family history of the disease. Inherited forms of breast cancer often appear in young women under the age of 50. In such families, some members may also be at higher risk for ovarian cancer. These mutations can be inherited from either a mother or father.
BRCA Genes. Inherited mutations in genes known as BRCA1 or BRCA2 are responsible for 30 - 50% of hereditary breast cancers, ovarian cancers, or both in families with a history of these cancers. According to some studies, the risk each gene carries is:
- Between 25 - 35% of BRCA1 carriers develop breast cancer by age 70.
- Between 35 - 50% of BRCA2 carriers develop the disease. BRCA2 genes also increase the lifetime risk of breast cancer in men.
These mutations are present in only about 0.5% of the overall population. However, certain ethnic groups -- such as Jewish women of Eastern European (Ashkenazi) descent -- have a higher prevalence (2.5%) of BRCA gene mutations.
Screening Guidelines for BRCA Genes. In 2005, the U.S. Preventive Services Task Force (USPSTF) released updated guidelines for BRCA testing. While women at high risk should be tested, the USPSTF does not recommend routine genetic counseling or testing for BRCA genes in low-risk women (no family history of BRCA 1 or 2 genetic mutations).
ESR Genes. Genetic variations in estrogen receptor genes (ESRs) may increase the risk for some women but offer protection to others. Mutations in the ESR1 and ESR2 genes may be associated with breast cancer susceptibility for Ashkenazi women over age 50 years.
Other Genetic Factors. Mutations in the tumor suppressor gene p53 are more common in the breast cancer tumors of African-American women than Caucasian women. Researchers have also identified other defective genes that contribute to breast cancer, such as NOEY2 (which is inherited from the father), CHEK2, and a mutant gene for the rare disorder ataxia-telangiectasia. (The disease itself is rare, but 1% of the population carries a single copy -- enough to increase the risk for breast cancer.) Finally, Cowden's syndrome is an inherited disorder caused by a defective PTEN gene that is associated with a higher risk of breast cancer.
Over-Exposure to Estrogen
Because growth of breast tissue is highly sensitive to estrogens, the more a woman is exposed to estrogen over her lifetime, the higher the risk for breast cancer.
Role of Estrogen Metabolism. A 2000 study suggested that the chance of estrogen increasing breast cancer risk in premenopausal women is related to how it is metabolized. In some women, very powerful estrogen products, or metabolites, are generated when metabolism takes place at a site on the estrogen molecule called C-16. These metabolites appear to pose a higher risk for breast cancer. (This metabolic effect does not appear to occur in postmenopausal women.) Fortunately, the study suggested that healthy diet and exercise may be able to alter this process.
Timing of Estrogen Exposure. Women's risk for breast cancer appears to be greater at specific times of estrogen exposure. For example, there is some evidence that starting one's period at an early age may be protective, in spite of the fact that this indicates a longer lifetime duration of estrogen exposure. Higher exposure in the womb (perhaps suggested by high birth weight), during pregnancy, or at menopause, however, does appear to increase risk.
Pregnancy and Abortion. Over the long term, women who have given birth even once have a lower risk than those who have not given birth. (Additional births do not seem to have any added impact.) However, there may be a higher risk for breast cancer in the immediate years after birth, particularly in older women.
Although a few studies have suggested a slightly increased risk for breast cancer in women who have had abortions, the weight of evidence does not support an association between abortion and breast cancer. However, interrupting a pregnancy does reduce the protective features of a full-term pregnancy.
Oral Contraception. Studies have been conflicting about whether estrogen in oral contraception increases the chances for breast cancer. A 2002 study supported an earlier major study, with both finding no evidence that OC use increases the risk for breast cancer, even in women who have taken them for 15 years of more or had taken them at young ages. In contrast, other studies have reported a higher risk in women who are current or recent users and in women who take them for more than four years before a first full-term pregnancy. Still, the risk for women taking OCs around menopause is unclear. Earlier research found a higher risk in women who used earlier forms of the pill containing high-dose estrogens and progestins (before 1975) and who had a family history of breast cancer.
Hormone Replacement Therapy. Several studies have reported a higher risk for breast cancer in postmenopausal women taking hormone replacement therapy (HRT), particularly with prolonged use and with formulations containing both estrogen and progestin. The longer a woman uses HRT, the higher her risk for breast cancer. HRT increases breast cancer density, making mammograms more difficult to read. This can cause cancer to be diagnosed at a later stage.
Progestin has been more strongly associated with risk for breast cancer than estrogen. However, some studies suggest that estrogen-alone HRT can pose a risk for breast cancer when women use it for longer than 10 years. A 2006 study also indicated that combined estrogen and testosterone therapy can double a woman’s risk for breast cancer.
At this time, most experts recommend that women use HRT only for short-term relief of menopausal symptoms. [For more information, see In-Depth Report #40: Menopause]
Breast Abnormalities
Abnormalities or Breast Conditions Suggesting a Higher Risk. Some breast formations or abnormalities should be watched and include the following:
- Dense breast tissue is associated with a higher risk for breast cancer. Studies suggest that in women with highly dense tissue have two to six times the risk of women with the least dense tissue. Genetic factors play a large role in breast density. Hormone replacement therapy also increases breast density.
- Benign proliferative breast disease or atypical cell growth, known as atypical hyperplasia, is a significant risk factor for breast cancer.
Benign Breast Conditions. Benign breast conditions are much more commonly seen on mammograms than cancer. And in the great majority of cases they pose no risk. Some common benign breast abnormalities that pose few or no risks include the following:
- Cysts. These mostly occur in women in their middle to late reproductive years and can be eliminated simply by aspirating fluid from them.
Click the icon to see an image of cysts in the breast.
- Fibroadenoma. These are solid benign lumps that occur in women between the ages of 15 and 30.
- Breast abscesses during breastfeeding.
Click the icon to see an image of a breast abscess.
- Nipple discharge. Discharge from the nipple is worrisome to patients, but is unlikely to be a sign of cancer. Unexplained discharge still warrants evaluation, however.
Click the icon to see an image of nipple discharge.
- Mastalgia. This is breast pain that occurs in association with or independently from the menstrual cycle. About 8 - 10% of women experience moderate to severe breast pain associated with their menstrual cycle. In general, breast pain does not need assessment unless it is severe and prolonged.
Physical Characteristics
The following physical characteristics have been associated with increased risk:
- Obesity increases the risk for all types of estrogen receptor-positive breast cancers. Women who gain weight after menopause are most at risk. (On a positive note, losing weight after menopause decreases breast cancer risk.) In postmenopausal women, estrogen is produced in fat tissue. High amounts of fatty tissue increase levels of estrogen in the body, leading to faster growth of estrogen-sensitive cancers.
- Estrogen is involved in building bone mass. Therefore, women with heavy, dense bones are likely to have higher estrogen levels and to be at greater risk for breast cancer.
- Some studies have found a greater risk for breast cancer in taller women, possibly due to the higher estrogen levels associated with greater bone growth. In one study, regardless of their actual height, women who reached their full height at age 13 or younger had a higher risk than those who attained maximum height at age 18, reflecting higher estrogen levels at an earlier age.
Environmental Factors
Exposure to Estrogen-like Industrial Chemicals. Chemicals with estrogen-like effects, called xenoestrogens, have been under suspicion for years. There has been particular concern with pesticides containing organochlorines (DDT and its metabolites, such as dieldrin) and pyrethroids (permethrin), but at this time evidence of any causal association is very weak.
Exposure to Diethylstilbestrol (DES). Women who took diethylstilbestrol (DES) to prevent miscarriage have a slightly increased risk for breast cancer. To date, this risk has not been seen in their daughters (commonly called "DES daughters"), who were exposed to the drug when their mothers took it during pregnancy.
Radiation Exposure. Heavy exposure to radiation is a significant risk factor for breast cancer. Children receiving high-dose radiation therapy face an increased risk for breast cancer in adulthood. Low-dose radiation exposure before age 20 may increase the risk for women with BRCA genetic mutations.
Viruses
Researchers theorize that viruses may be involved in some types of breast cancers. A study of breast cancer samples taken from Tunisian women in North Africa found similarities with a virus known to cause breast cancer in mice. The samples were compared with those taken from women living in other global regions. The researchers suggested that a human breast cancer virus may be more prevalent in specific parts of the world.
Insulin-Like Growth Factor
Insulin-like growth factor 1 is an important growth hormone during development in the womb and childhood. It has powerful properties that increase cell proliferation, and high concentrations have now been linked to cancers, including premenopausal breast cancer. In fact, it may be one of the factors that are responsible for the association between height and breast cancer. More research is needed to verify a possible role of insulin-like growth factor 1 in breast cancer development.
