Replacement estrogens and risk of gynecologic cancers and breast cancer

The two cancers specific to women for which substantial research on their relationship to exogenous estrogens has been reported are endometrial cancer and breast cancer. With the former, the link to estrogen use is well established. The estrogen use patterns associated with increased risk of endometrial cancer are characteristic of a promotional agent. The example serves as a prototype model for the study of an adverse health effect subsequent to a prescribed medication. However, modification in estrogen prescribing patterns have lowered significantly the endometrial cancer risk for patients. A relationship between estrogen replacement therapy and breast cancer is difficult to assess. Despite biologic plausibility, large epidemiologic studies have shown no association between estrogen use and breast cancer occurrence. Those studies suggesting a relationship find it concentrated in the high dose estrogen products and possibly among women who have had a prior bilateral oophorectomy. A convincing resolution to the current uncertainty is likely to require new approaches in laboratory, clinical, and epidemiologic research. Larger studies investigating more refined hypotheses within the same conceptual confines are unlikely to be productive.