[MOL] Risks for Breast Cancer [01865] Medicine On Line

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[MOL] Risks for Breast Cancer


Celia Byrne, Ph.D.*

Breast cancer is the most common form of cancer (other than skin) and a leading cause of cancer mortality among women in the United States. Breast cancer rates in the United States are among the highest in the world. White women in the San Francisco Bay area experienced the highest incidence among 162 areas reporting incidence data to the IARC, with an annual rate of 104.2 per 100,000, adjusted to the world standard population (Parkin et al., 1992).

Incidence rates increase dramatically with age. While the rate of increase in breast cancer incidence is greatest in women under age 50, the majority of cases occur after age 50. Incidence rates in women before the age of 45 are higher among blacks; after the age of 45, they are higher for whites. Women of higher socioeconomic status, married women, women living in urban versus rural areas, and women in northern states have the highest rates.

From 1973 to 1991, invasive breast cancer incidence in the United States increased 25.8 percent in whites and 30.3 percent in blacks, or roughly 2 percent per year (Ries et al., 1994). The reason for the increase in breast cancer incidence is not clearly understood, but may be explained, in part, by a 75 percent rise in use of mammography (MMWR, 1990), since much of the increase in invasive breast cancer has been for the lowest-stage tumors. However, the increased rates cannot be completely explained by increased use of mammography, suggesting that changes in other breast cancer risk factors may also be occurring. Based on the 1983-90 statistics, the five-year relative survival rates of breast cancer were 81.6 percent for white women and 65.8 percent for black women in the United States (Ries et al., 1994). The racial disparity in survival persisted for each stage of disease.

Both genetic and environmental factors are believed to play a role in a woman's risk of developing breast cancer. If either a woman's mother or sister has breast cancer, the woman's risk increases about two to three times. Having both a mother and a sister with breast cancer increases a woman's risk up to six-fold. If that relative had bilateral breast cancer or was diagnosed at an early age, the risk may be further increased (Kelsey and Gammon, 1990). In small groups of families, the patterns of breast cancer incidence seems to be consistent with known patterns of genetic inheritance (Wright, 1990). Miki et al. reported the first cloning of a breast cancer gene (BRCA-1) in 1994. It is estimated that 86 percent of the women with a mutation in the BRCA-1 gene will develop breast cancer by age 70. However, only between 5 and 10 percent of all breast cancers seem to be attributable to an inherited genetic mutation. A second breast cancer gene (BRCA-2) has been located but not yet identified. Studies of migrants who immigrate from low-incidence areas to high-incidence areas have found that the rates of breast cancer increase to that of the new country, reflecting changes in lifestyle and environmental factors, showing that international differences in rates are not due to genetic factors.

It is well recognized that certain reproductive events, and the age at which they occur, are strong determinants of subsequent breast cancer risk. The most consistent determinant of risk in various populations is the woman's age at first full-term pregnancy. Women with a first full-term pregnancy after age 30, and women who have never borne a child have about a two- to three-fold increased risk of breast cancer compared to women having a full-term pregnancy before age 20.

The greater number of women who are delaying childbirth or remaining childless may explain some of the recent increased incidence of breast cancer. Early menarche and late menopause increase a woman's risk, while removal of both ovaries, before menopause, reduces risk. Several recent studies suggest that subsequent births are associated with a further reduction in the risk of breast cancer, even after considering correlated effects of the age at first pregnancy. The effect of lactation is still not clear, although there is the suggestion of a protective effect the greater the number of months a woman breast-feeds (Kelsey et al., 1993). These reproductive factors are often thought to affect the risk of breast cancer by their effects on a woman's hormonal status.

Because of the relationship between endogenous hormones and breast cancer risk, much concern has been raised about the use of exogenous hormones. Most studies suggest no effect from oral contraceptive use on breast cancer incidence. However, some recent studies suggest a possible increase in breast cancer at an early age (before age 45) among long-term oral contraceptive users, and those who started taking oral contraceptives at a young age. There is also evidence that use of estrogen replacement therapy may slightly increase the risk of breast cancer, particularly among long-term users and those who used high doses of estrogen (Brinton and Schairer, 1993). Little is known about risk from the frequently prescribed estrogen/progestin combination. Further study of the effects of oral contraceptives and hormone replacement therapy is needed, as any associated increases in risk could affect many women.

A history of biopsy-confirmed benign breast disease is also recognized as a risk factor for breast cancer. However, the risk is not uniform for all types of benign breast disease. Atypical hyperplasia apparently indicates an especially high risk (Bodian, 1993). Women with a high degree of dense breast tissue (Dy and P2 patterns), visible on mammography, have a three to four times increased risk of breast cancer (Oza and Boyd, 1993). A diagnosis of breast, ovarian, or endometrial cancer has also been shown to be associated with an increased risk of subsequent breast cancer.

Among postmenopausal women, breast cancer risk increases with weight and body mass. Two recent studies suggest that not only is body mass positively associated with postmenopausal breast cancer, but the distribution of weight may also be a factor (Kelsey and Gammon, 1990). Lean women appear to be at increased risk of premenopausal onset breast cancer, perhaps in part reflecting difficulties of disease detection at early ages in obese women.

Disparate levels of dietary fat consumption have been a major focus in attempting to explain some of the international and geographical differences in breast cancer incidence (the high rates in Western industrialized nations and the low rates in Asia, Latin America, and Africa). However, the results of epidemiologic studies reported to date do not resolve this issue. A few studies reported a weak increase in breast cancer risk among women consuming high fat diets, while several large prospective studies that evaluated effects of adult dietary fat intake show little if any association with breast cancer risk (Hunter and Willett, 1993).

Recent studies have shown a fairly consistent though small effect of alcohol consumption on breast cancer risk. In a summary analysis of epidemiologic studies, breast cancer risk increased between 40 and 70 percent with about two drinks daily (Longnecker et al., 1988).

Exposure to high doses of radiation, from puberty through the childbearing years--when breast tissue undergoes rapid proliferation--is known to increase the risk of breast cancer. Recent findings indicate that exposure to high doses of radiation, even in infancy, increases the risk of breast cancer in later life. The effects of low-dose radiation from mammography are considered minimal. Studies have shown that the benefits from mammography in reducing the rate of breast cancer deaths for women over 50 outweigh any possible risks (Kelsey and Gammon, 1990). However, further research is needed on the risks/benefits of mammography for women under the age of 50.

While many factors have been associated with the risk of breast cancer, most of the "established" risk factors for breast cancer are associated with only a moderate two to three times increased risk, suggesting that multiple factors may play a role in each woman's disease and that unrecognized factors may exist. In addition, only a small proportion of the cases are accounted for by known risk factors (Kelsey and Gammon, 1990), indicating the need for further research.

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