Identification of risk factors is important in explaining the variation in breast cancer incidence across different populations. Risk factors can also identify women who may benefit from increased surveillance or preventive treatments.

Table 33.2 outlines the major established risk factors for breast cancer, which include family history of breast cancer, early age at menarche, late age at birth of first child, nulliparity, late age at menopause, benign breast disease with proliferative changes, radiation exposure, and hormone replacement therapy. Given the heightened risk of breast cancer with age, all older women should be considered at increased risk.

The relationship between exogenous hormone therapy and breast cancer risk may be of particular concern to older women and their physicians. Recent meta-analyses reveal small but statistically significant increases in risk (relative risks ranging from 1.02 to 1.35) of breast cancer among women exposed to hormone replacement therapy.

Risk appears to increase with current use and longer duration of use; it also appears to be reduced after cessation of hormone replacement therapy. These findings are consistent with the evidence that postmenopausal women with higher concentration of endogenous estrogen levels have a greater risk of developing breast cancer than women with lower estrogen levels. Recent studies have also found statistically significant increases in risk in women taking both estrogen and progestin compared to those taking estrogen alone for hormone replacement therapy. The decision to use hormone replacement therapy is complex and should entail careful consideration of the risks, including baseline breast cancer risk in an individual and potential benefits.

There are several other less well established risk factors for breast cancer that have also been studied extensively, including obesity, height, alcohol consumption, and oral contraceptive use. Of these, moderate alcohol consumption has most consistently been associated with increased breast cancer risk. The influence of diet on breast cancer risk has attracted great interest. The large variation in international breast cancer incidence rates suggests a possible relationship between breast cancer and diet.

Many studies have examined the effects of specific dietary components on breast cancer risk. Despite the lack of evidence that specific components such as fiber or individual vitamins and minerals confer any significant protective effect, a diet high in fruits and vegetables may decrease breast cancer risk. Although national per capita fat consumption correlates with incidence and mortality from breast cancer, investigators have been unable to detect any relation between risk of breast cancer and total fat intake or consumption of specific types of fats.

Studies of the relationship between energy balance and breast cancer have been more revealing. Although being overweight during early adult life has been associated with a lower incidence of premenopausal breast cancer, weight gain after age 18 is associated with a significantly increased risk of postmenopausal breast cancer. The increased risk associated with weight gain and obesity in later adult life has been hypothesized to be due to the increased estrogen levels in these women secondary to increased production in adipose tissue. Furthermore, these findings would appear to be consistent with the possible influence of physical activity on breast cancer risk. Limited evidence suggests that physical activity is protective against breast cancer. This benefit may occur because exercise influences body fat stores, the principal source of estrogen in postmenopausal women. However, to date, the association of physical activity and decreased breast cancer risk is more pronounced among premenopausal women.

With the exception of inherited susceptibility genes (see following), all the identified risk factors are associated with only weak to moderate increases in risk. Women without any identifiable risk factors till have a considerable lifetime risk of breast cancer (approximately 7% through age 80). All women may improve their overall health, perhaps decreasing breast cancer risk, by maintaining a healthy weight, avoiding cigarettes, limiting alcohol consumption, getting regular exercise, and avoiding nondiagnostic ionizing radiation. Nevertheless, no lifestyle modifications have been proven to prevent or definitively lower the risk of breast cancer.