Hormone alterations in breast cancer: examining the hypotheses.

Many of the epidemiologic risk factors for breast cancer offer clinicians little help in anticipating who is likely to be struck with the disease or how to prevent it. There are only a handful of clinically significant risk factors for breast cancer. These include being a woman, growing older, already having breast cancer in 1 breast, and having a first-degree relative (mother, sister, or daughter) who has been diagnosed with breast cancer. Most risk factors have a weak association with breast cancer, occur too infrequently, or are physiologic events not amenable to intervention. In recent years, the search for breast cancer causes has led to the identification of genetic markers that seem to predispose some women to breast cancer. For decades, however, researchers have been assessing and analyzing hormonal changes in the hope of finding a predictable breast cancer marker or cause that can easily be manipulated to prevent or more effectively treat the disease. Nearly a dozen hormonal hypotheses of breast cancer causes have been proposed -- among them estrogen excess, low luteal-phase progestational activity, adrenal androgen deficiency, ovarian androgen excess, melatonin deficiency, prolactin excess, and thyroid insufficiency. For most, the data are equivocal and inconclusive. The androgen deficiency hypotheses, however, may have some bearing on premenopausal breast cancer, and the ovarian dysfunction hypothesis may have some bearing on postmenopausal breast cancer.