Hormone Therapy in Preventing Endometrial Cancer in Patients With a Genetic Risk For Hereditary Nonpolyposis Colon Cancer

PRIMARY OBJECTIVES: I. The primary objective is to evaluate the effect of progesterone therapy versus combination estrogen and progesterone therapy on potential surrogate endpoint biomarkers (SEBs) relevant to endometrial carcinogenesis. II. To evaluate changes in histology and ultrasound appearance of the endometrium in women with HNPCC after 3 months of progesterone therapy versus combination estrogen and progesterone therapy compared with baseline. III. To establish a point estimate of the baseline frequency of endometrial abnormalities looking at histological and molecular markers in a cohort of females carrying an HNPCC gene mutation. OUTLINE: Patients are randomized to 1 of 2 arms. All patients undergo a baseline transvaginal ultrasound and endometrial biopsy. Arm I: Patients receive medroxyprogesterone intramuscularly once on day 1. Approximately 90 days after the injection, patients undergo a repeat transvaginal ultrasound and endometrial biopsy. Arm II: Patients receive oral contraceptive pills (OCP) comprising ethinyl estradiol and norgestrel once daily on days 1-21. Treatment repeats every 28 days for 3-4 courses (3-4 packs of OCP) in the absence of unacceptable toxicity. Approximately 1 week after starting the fourth pack of OCP, patients undergo a repeat transvaginal ultrasound and endometrial biopsy. Patients are followed at 6 weeks and are encouraged to return in 6 months to participate in continued endometrial screening.