The etiology of breast cancer--from epidemiology to prevention.

Breast cancer is likely caused by the interaction of exposure to environmental carcinogens at an early age, resulting in initiation of neoplastic transformation and growth factors that determine the likelihood of progression to clinical disease. The environmental carcinogens are numerous (each contributing relatively little to overall risk) and probably interact with genetic "host susceptibility". Most women probably have subclinical breast cancer. The growth of the breast cancer is related to sex-hormone levels at the breast and stimulation of local growth factors. Genetic factors (i.e. host susceptibility including polymorphisms related to the enzymes that affect hormone levels, estrogen/progesterone receptors, and protein synthesis) are probably very important. Reproductive and menstrual patterning during the premenopause, especially related to pregnancy, menstrual cycling and lactation are very important determinants of the risks of breast cancer. More attention needs to be placed on the determinants of menstrual cycling and hormone levels in premenopausal women, especially the relationship of obesity, fat distribution and exercise. The degree of obesity, age at onset of obesity, weight gain (peri- to postmenopausal), and possibly body fat distribution are the major determinants of postmenopausal estrogen levels are key risk factors for postmenopausal breast cancer. Dietary fat, fiber, and perhaps other nutrients, also contribute to blood estrogen levels. Other hormones, especially insulin and insulin-like growth factors, and possibly testosterone and androgens, may also contribute to the increased risk of breast cancer. The reduction of breast cancer incidence and mortality will depend, primarily, on modifications of women's lifestyles which would move them from higher to lower estrogen characteristics.