Do female sex hormones initiate breast cancer? A review of the evidence.

Over the past 2 years, the media have highlighted a number of epidemiological articles which suggest that estrogen therapy, with or without progestogens, is responsible for initiating breast cancer in postmenopausal women. However, the essential biological mutations necessary to induce a new breast cancer suggest that the increase in diagnosis is due to promotion of an already existing, but undiagnosed, oncogenic change, rather than to sex hormones initiating malignant mutations. In this review, anomalies in the hypothesis that hormonal therapy causes breast cancer are identified, the sequence of mutations which must occur prior to development of an invasive breast cancer are defined and the influence of the sex hormones on these changes is briefly reviewed. The conclusion is that sex hormones are mitogenic but not oncogenic.