Abstract B33: Reproductive and hormonal risk factors in relation to ovarian cancer survival and platinum resistance.

Introduction: Ovarian cancer survival is poor particularly for women with platinum-resistant disease. Therefore evaluating pre-diagnostic risk factors that are associated with ovarian cancer survival and platinum resistance in particular may help identify women who will not benefit from standard therapy. However, limited research has assessed pre-diagnostic reproductive and hormonal factors in relation to ovarian cancer survival and no studies have assessed these factors with platinum resistance. Objective: To evaluate the association of pre-diagnostic reproductive and hormonal factors with both ovarian cancer survival and platinum resistance among ovarian cancer patients. Methods: We included 1,648 cases of invasive epithelial ovarian cancer from a population-based case-control study with cases and controls recruited in Eastern Massachusetts and New Hampshire from 1992-2008. Reproductive and hormonal factors, including oral contraceptive use, parity, tubal ligation and endometriosis, were assessed during in-person interviews. Invasive ovarian cancer cases who received platinum chemotherapy and had medical record follow-up data (n=610) were included in the analyses on platinum resistance, which was defined as a recurrence within the first six months after the end of platinum-based chemotherapy. We used Cox proportional hazards models to calculate overall ovarian cancer survival and platinum resistance controlling for age, enrollment wave, reproductive factors, and tumor histology and stage. The same reproductive and hormonal factors were assessed for ovarian cancer survival and platinum resistance. As the cause of death was not known for all cases, we also restricted follow-up to the first five years when the vast majority of deaths should be from ovarian cancer in a secondary analysis. Results: We observed 906 deaths during 13,920 person-years of follow-up. Self-report of a physician diagnosis of endometriosis was associated with a 28% (95% CI: 0.55-0.95; p=0.02) decreased risk of death from ovarian cancer. We observed no association between oral contraceptive use, parity, age at first birth, and ovulatory years and ovarian cancer survival (p>0.17). Restricting analyses to the first five years did not substantially change the results. In preliminary analyses, 162 of the 610 women with platinum-based therapy had a disease recurrence within six months of ending treatment over 3,216 person-months of follow-up. Ever having a spontaneous or induced abortion was associated with a 44% (95% CI: 1.00-2.07; p=0.05) increased risk of platinum resistance but was not associated with overall ovarian cancer survival (p=0.18). Additionally, there was a suggestion that increasing age at menarche (Hazard ratio (HR): 1.13; 95% CI: 0.99-1.29 per year; p=0.07) and physician-diagnosed endometriosis (HR: 0.45; 95% CI: 0.19-1.05; p=0.06) were associated with platinum resistance. No association was observed for oral contraceptive use, parity, age at first birth, and ovulatory years (p>0.53), although the results were based on a small sample size. Conclusion: Increasing age at menarche and ever having a spontaneous or induced abortion were associated with an increased risk of platinum chemotherapy resistance. Additionally, physician-diagnosed endometriosis was associated with a reduced risk of ovarian cancer death and a suggestion of a reduced risk of platinum-resistance after adjusting for various factors including tumor histology. Although endometriosis increases the risk of endometrioid and clear cell tumors, which tend to have a more favorable prognosis, our data suggest endometriosis may improve survival through pathways other than tumor histology. Citation Format: Amy L. Shafrir, Ana Babic, Rulla M. Tamimi, Bernard A. Rosner, Shelley S. Tworoger, Kathryn L. Terry. Reproductive and hormonal risk factors in relation to ovarian cancer survival and platinum resistance. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr B33.