Background: More than three decades of epidemiologic studies have identified numerous risk factors for breast cancer. These factors have been estimated to account for only 20-25% of disease occurrence. However, among these factors, several are related to sex steroid hormones: sex of the affected individuals (women), early age of menarche and late age of menopause, parity, late age at first pregnancy, and obesity in postmenopausal women.
Methods: Theoretical models and laboratory data support hormonal mechanisms of carcinogenesis, particularly as they relate to proliferation of breast ductal epithelium and terminal end bud growth and differentiation in the lobules of the breast. The recent introduction of biologic markers and molecular epidemiology allows for studies that use laboratory technology in the context of epidemiologic research.
Results: This paper summarizes the epidemiologic literature on exogenous hormones, addresses the issue of endogenous steroid hormone levels and estrogen metabolism in serum and breast tissue in premenopausal and postmenopausal women with and without cancer, speaks to the cellular mechanisms of action of estrogen and progesterone, and highlights some of the biologic markers relevant to studies of breast cancer and precursor lesions, with particular emphasis on those that may be hormonally induced or altered.
Conclusions: These markers must be better defined in terms of breast cancer pathogenesis. Studies are needed to evaluate the direct effects of behavioral/environmental risk factors on relevant biomarkers as well as to assess the interactions of epidemiologic factors and biomarkers on risk of breast cancer.