Eva Szabo

Pilot Study of Daily Exemestane in Women with Endometrial Intraepithelial Neoplasia or Low-Grade Endometrial Cancer

Abstract Purpose: To evaluate exemestane, an aromatase inhibitor, as a preventive intervention for endometrial cancer. Experimental Design: This is a multicenter, single-arm, “window of opportunity” pilot study of exemestane (25 mg daily for 21–42 days) in postmenopausal individuals undergoing hysterectomy for endometrial intraepithelial neoplasia (EIN) or low-grade endometrial cancer. The primary objective is to determine the change in proliferation, measured by Ki-67 expression, in pre- and posttreatment endometrial tissue specimens. Secondary outcomes include measurement of circulating serum estradiol and progesterone levels, pathologic response, tissue biomarkers, safety, and adverse effects. Results: Forty participants were accrued to the study. The mean body mass index was 40.3 (range, 22.8–60.5, SD = 9.8). Preoperative diagnoses included EIN (n = 11, 27.5%), grade 1 endometrial cancer (n = 26, 65%), and grade 2 endometrial cancer (n = 3, 7.5%). Median Ki-67 score decreased from 40.7% [IQR (33.9, 50.3)] at baseline to 18.1% [IQR (8.8, 31.8)] at surgery, representing a median absolute change from baseline of 20.4% [IQR (−29.9, −6.7), P < 0.001]. In a matched historic control cohort, participants also had a decrease in Ki-67 score with a median absolute change from baseline of −6.7% [IQR (−12.7, −1.3), P< 0.001]. However, the decrease in Ki-67 was greater in the study participants than the historic controls, with a median difference between the groups of −13.4% [IQR (−23.3, 6.9), P ≤ 0.01]. Both tissue estrogen receptor and progesterone receptor expression declined significantly with exemestane treatment (P < 0.001). However, serum estradiol levels did not change between baseline and after treatment (P = 0.16). Conclusions: In this pilot study, exemestane demonstrated antiproliferative effects in EIN and low-grade endometrial cancer. This agent warrants further evaluation for the prevention of endometrial cancer.

Cancer Prevention in Primary Care: Perception of Importance, Recognition of Risk Factors and Prescribing Behaviors

Acceptability and uptake of cancer preventive interventions is associated with physician recommendation, which is dependent on physician familiarity with available preventive options. The goal of this study is to evaluate cancer prevention perceptions, understanding of breast and ovarian cancer risk factors, and prescribing behaviors of primary care physicians. We conducted cross-sectional. Web-based survey of 750 primary care physicians (250 each for obstetrics/gynecology, internal medicine, and family medicine) in the United States. Survey respondents were recruited from an opt-in health care provider panel. Perception of importance and the practice of recommending general and cancer-specific preventive screenings and interventions significantly differed by provider type. These perceptions and behaviors reflected the demographics of the population that the primary care physicians see within their respective practices. The majority of respondents recognized genetic/hereditary risk factors for breast or ovarian cancer, while epidemiologic or clinical risk factors were less frequently recognized. Prescribing behaviors were related to familiarity with the interventions, with physicians indicating that they more frequently reinforced a specialist's recommendation rather than prescribed a preventive intervention. Cancer prevention perceptions, recognition of cancer risk factors, and prescribing behaviors differ among practice types and were related to familiarity with preventive options. Cancer prevention education and risk assessment resources should be more widely available to primary care physicians.