Breast Cancer

Description

Alternative Names

Risk Factors

Experts estimate that about 211,300 new cases of invasive female breast cancer and 55,700 cases of in situ breast cancer will be diagnosed in 2003. About 1,300 breast cancers will be diagnosed in men during the year.

At this time, age is a major identifiable risk factor. More than 80% of breast cancer cases occur in women over 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 one in 217.
• At age 50, they are one in 50.
• If a woman lives to be 85, the odds of her having breast cancer are one in eight.

Ethnicity

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 also are less likely to have access to effective treatments. (It should be noted that 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, which often appears in young women under the age of 50. In such families, some members may also have developed ovarian cancer as well.

Prior to menopause, a mass on the ovary that is smaller than 2 centimeters is probably a follicle cyst that will go away on its own. However, if the growth is larger and doesn't go away over the course of a few menstrual cycles, then it may need to be removed.

Certain known genes predispose women to this cancer are as follows:

BRCA Genes. Inherited mutations in genes known as BRCA1 or BRCA2 are now believed to be responsible for 30% to 50% of hereditary breast cancers, ovarian cancers, or both in families with a history of these cancers. According to some studies, the risk each carries appears to be as follows:

• Between 25% and 35% of BRCA1 carriers will develop breast cancer by age 70.
• Between 35% and 50% of BRCA2 carriers develop the disease. BRCA2 genes may confer an increased risk of breast cancer in men as well as in women (which is extremely low).

These mutations can be passed down to the daughter by either the mother or the father.

These mutations are present in only about 0.5% of the U.S. or U.K. population overall but occur in about 2.5% of all Jewish women of Eastern European (Ashkenazi) descent. This prevalence in a relatively large population makes mutations to BRCA1 and BRCA2 the most common serious genetic disease known in any population group. These mutations are not restricted to the Ashkenazi population and may occur in women of any ethnicity, including women of Asian and African descent. It should be noted, however, that these mutations still account for a minority of breast cancer cases overall -- only 7% of all breast cancer cases in Eastern European Jewish women, and far fewer in the general population.

Other Genetic Factors. Researchers have also identified other defective genes that contribute to breast cancer, such as NOEY2 (which is inherited from the father) and a mutant gene for the rare disorder ataxia-telangiectasia. (The disease itself is rare, but 1% of the population carries a single copy, which is 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 suggests 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.) It should be noted that 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 (ages 45 to 64) 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. A number of studies have now 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. (Progestin has been more strongly implicated in the risk for breast cancer than estrogen.) Prolonged use increases the risk. A major study on HRT was stopped because of a slightly higher risk for breast cancer, although it should be noted the absolute risk is still quite small. There was no effect on mortality rates from breast cancer in HRT users. There has been some evidence to suggest that breast cancer in HRT users may have a more favorable outlook, including a lower recurrence rate, than nonusers. Breast tissue density increases with HRT, making mammograms more difficult to read.

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% to 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 greater or lesser risk:

• A number of studies have linked obesity to breast cancer after (but not before) menopause. The risk appears to be greater in women who began to gain weight after age 18. One study, in fact, suggested that being heavier as a child conferred a lower risk for breast cancer after menopause. (Estrogen levels are lower in the presence of high fat levels in premenopausal women.)
• Estrogen is involved in building bone mass. Therefore, women with heavy, dense bones are likely to have higher estrogen levels and 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 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 (e.g., DDT and its metabolites, such as dieldrin) and pyrethroids (e.g., 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.

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.