Hormone prevention strategies for breast, endometrial and ovarian cancers

The development of effective prevention strategies for breast, endometrial and ovarian cancers (CA), based on hormonal responsiveness, is a paramount opportunity in the care of women at risk for these malignancies. Breast CA prevention, utilizing Selective Estrogen Receptor Modulators (SERMs) is a well-established paradigm in the management of high risk women. Aromatase inhibitors (AI) and prophylactic bilateral salpingo-oophorectomy are presently under investigation for that same purpose. Endometrial carcinoma (EC), specifically Type 1, is the most common gynecologic malignancy in the United States. Its positive association with excess estrogen exposure provides significant opportunity for hormonal chemoprevention. Population-based studies have established that oral contraceptives (OC) significantly decrease the incidence of this malignancy. This risk reduction lasts up to 20 years after discontinuation of OCs. The association between elevated BMI and risk of developing EC (due to increased peripheral estrogen exposure) has prompted investigation into the role of weight reduction in EC prevention. The prevention of epithelial ovarian cancer (EOC) is of particular interest given its high mortality rate and the lack of a cost-effective screening program. OC usage significantly diminishes the incidence of EOC, in both the general population, as well as in patients with BRCA 1 or 2 mutations. Risk reduction is greatest with prolonged usage and persists for more than 30 years after OC use, but diminishes over time. Prospective, randomized trials, designed to control for all known variables, are mandatory to fully assess the potential for hormonal chemoprevention in breast, endometrial and ovarian cancers.