Background: Although oral contraceptive (OC) use is ubiquitous in the United States, the influence of OCs on the development of cancers is not fully understood. In 2013, an Agency for Healthcare Research and Quality Evidence Report identified several data gaps with regard to OC use and its associations with cancer, including a need to understand if associations are consistent across subpopulations of users, including smokers and obese women. Methods: To address this data gap, we used Cox proportional hazards models to examine duration of OC use (never/less than 1 year [reference], 1 to 4, 5 to 9, 10+ years) and subsequent development of incident ovarian or endometrial cancer among participants in the NIH-AARP Diet and Health Study. We further examined effect modification by a variety of modifiable risk factors, including body mass index (BMI), cigarette smoking, alcohol consumption, and physical activity, via interaction terms and a likelihood ratio test. Models were adjusted for age, race, age at menarche and the modifiers of interest. Results: For ovarian cancer (n=1,241 cases, 149,502 non-cases), a reduction in risk was conferred by OC use that linearly decreased with duration of use (hazard ratios [HR] ranging from 0.83 to 0.60 across categories of duration). We also identified linear, inverse associations between increasing duration of OC use and ovarian cancer risk across most potential modifiers. Some of the most pronounced reductions were observed among long-term OC users (10+ years) who were current smokers (HR compared to non-users of 0.44, 95% confidence interval [CI] 0.20, 0.97) or who engaged in moderate physical activity (0.44, CI 0.23, 0.85). For endometrial cancer (n=2,337 cases, n=112,132 non-cases), we observed pronounced reductions in risk associated with long-term OC use among women with obese BMIs (0.36, CI 0.25, 0.52) and those who exercised rarely (0.40, CI 0.29, 0.56) or moderately (0.50, CI 0.33, 0.75). However, long-term use was not associated with risk reductions among women with BMIs of less than 25 or among women who exercised at least three times per week. Conclusions: OC use is consistently associated with reduced risks of ovarian cancer across most strata of modifiable risk factors. For endometrial cancer risk, OC use seems to offer the greatest risk reduction among women in previously identified high-risk categories (i.e., overweight/obese BMI, physically inactive), findings which merit further discussion as these women may be more likely to have comorbid conditions that would contraindicate OC use (e.g., hypertension, diabetes).

Citation Format: Kara A. Michels, Louise A. Brinton, Ruth M. Pfeiffer, Britton Trabert. Duration of oral contraceptive use and the prevention of gynecologic cancers: Modification by modifiable factors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3013. doi:10.1158/1538-7445.AM2017-3013