Epidemiology of endocrine-related risk factors for breast cancer.

Ovarian and other hormones are major determinants of breast cancer risk. Particularly important is the accumulative exposure of the breast to circulating levels of the ovarian hormones estradiol and progesterone. A number of breast cancer risk factors can be understood in light of how they affect women's hormone profiles. Age is a marker for the onset and cessation of ovarian activity. Racial differences in hormone profiles correlate with breast cancer incidence patterns. Age at menarche not only serves as the chronological indicator of the onset of ovarian activity, but as a predictor of ovulatory frequency during adolescence and hormone levels in young adults, and has a long-lasting influence on risk. Age at menopause, another established breast cancer risk factor, marks the cessation of ovarian activity. Pregnancy history and lactation experience also are hormonal markers of breast cancer risk. Postmenopausal obesity, which is associated with higher levels of estrogen following cessation of ovarian activity, increases breast cancer risk, whereas physical activity, which can limit menstrual function, reduces risk. A relatively recent area of investigation is prenatal exposures like preeclampsia and low birth weight; both may be associated with lower in utero exposure to estrogen and also may predict lower breast cancer risk as an adult. Improved understanding of these exposures and their potential interactions with breast cancer susceptibility genes may, in the future, improve our prospects for breast cancer prevention.