Chemoprevention of endometrial cancer in Lynch syndrome: a step forward

Lynch syndrome is one of the most common hereditary cancer syndromes. Although Lynch syndrome is associated with increased risk for developing colorectal, endometrial, and other cancers specialized screening, risk-reducing surgery, and chemoprevention offer promise for reducing morbidity and mortality. Frequent colonoscopic surveillance has proven effective for early detection and prevention of Lynch syndrome-associated colorectal cancer; however, the optimal strategy for managing endometrial cancer risks in women with germline mutations in DNA mismatch repair genes has yet to be determined. In this issue of Cancer Prevention Research, Lu and colleagues report their findings of a phase II prospective, multicenter randomized trial comparing the effects of oral contraceptive pills and Depo-Provera on endometrial proliferation in women with Lynch syndrome. Although short-term hormonal treatment with either modality altered endometrial proliferation indices, it remains unknown whether hormonal suppression actually reduces endometrial cancer risk in women with Lynch syndrome. This trial represents the first of its kind in evaluating agents which might offer protection against Lynch syndrome-associated endometrial cancer and provides preliminary data regarding potential biomarkers for early detection of endometrial neoplasia. The investigators' experience with this trial also offers insights regarding the various technical and scientific challenges inherent in chemoprevention research.