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Author(s): Lee, Alice W; Rosenzweig, Stacey; Wiensch, Ashley; Australian Ovarian Cancer Study Group; Ramus, Susan J; Menon, Usha; Gentry-Maharaj, Aleksandra; Ziogas, Argyrios; Anton-Culver, Hoda; Whittemore, Alice S; Sieh, Weiva; Rothstein, Joseph H; McGuire, Valerie; Wentzensen, Nicolas; Bandera, Elisa V; Qin, Bo; Terry, Kathryn L; Cramer, Daniel W; Titus, Linda; Schildkraut, Joellen M; Berchuck, Andrew; Goode, Ellen L; Kjaer, Susanne K; Jensen, Allan; Jordan, Susan J; Ness, Roberta B; Modugno, Francesmary; Moysich, Kirsten; Thompson, Pamela J; Goodman, Marc T; Carney, Michael E; Chang-Claude, Jenny; Rossing, Mary Anne; Harris, Holly R; Doherty, Jennifer Anne; Risch, Harvey A; Khoja, Lilah; Alimujiang, Aliya; Phung, Minh Tung; Brieger, Katharine; Mukherjee, Bhramar; Pharoah, Paul DP; Wu, Anna H; Pike, Malcolm C; Webb, Penelope M; Pearce, Celeste Leigh | Abstract: BackgroundParity is associated with decreased risk of invasive ovarian cancer; however, the relationship between incomplete pregnancies and invasive ovarian cancer risk is unclear. This relationship was examined using 15 case-control studies from the Ovarian Cancer Association Consortium (OCAC). Histotype-specific associations, which have not been examined previously with large sample sizes, were also evaluated.MethodsA pooled analysis of 10 470 invasive epithelial ovarian cancer cases and 16 942 controls was conducted. Odds ratios (ORs) and 95% confidence intervals (CIs) for the association between incomplete pregnancies and invasive epithelial ovarian cancer were estimated using logistic regression. All models were conditioned on OCAC study, race and ethnicity, age, and education level and adjusted for number of complete pregnancies, oral contraceptive use, and history of breastfeeding. The same approach was used for histotype-specific analyses.ResultsEver having an incomplete pregnancy was associated with a 16% reduction in ovarian cancer risk (OR = 0.84, 95% CI = 0.79 to 0.89). There was a trend of decreasing risk with increasing number of incomplete pregnancies (2-sided Ptrend l .001). An inverse association was observed for all major histotypes; it was strongest for clear cell ovarian cancer.ConclusionsIncomplete pregnancies are associated with a reduced risk of invasive epithelial ovarian cancer. Pregnancy, including incomplete pregnancy, was associated with a greater reduction in risk of clear cell ovarian cancer, but the result was broadly consistent across histotypes. Future work should focus on understanding the mechanisms underlying this reduced risk.

BACKGROUND: Ovarian cancer is associated with reproductive and hormonal factors including parity, breastfeeding, and use of oral contraceptives. However, the effect of incomplete pregnancies, including both induced and spontaneous abortions, is unclear. The most recent assessments of this association include analyses of two Australian case-control studies and the European Prospective Investigation into Cancer and Nutrition (EPIC) study in which both report no significant association between incomplete pregnancies and risk of ovarian cancer. However, a review of these findings and those included in a systematic review are suggestive of an overall protective effect among women who have had an incomplete pregnancy compared to those who have not. METHODS: To study the incomplete pregnancy-ovarian cancer association in detail, we pooled epidemiologic data from 16 population-based case-control studies from the Ovarian Cancer Association Consortium (OCAC). An incomplete pregnancy was defined as any pregnancy lasting fewer than six months in duration that did not result in a live birth. The effects of ever having an incomplete pregnancy as well as the number of incomplete pregnancies were evaluated using conditional logistic regression after considering potential confounders. Histotype-specific analyses were also conducted to determine the association between incomplete pregnancies and high-grade serous, low-grade serous, mucinous, endometrioid, and clear cell ovarian cancer. RESULTS: A total of 11,217 ovarian cancer cases and 18,588 controls was included in our analysis. We found that women who ever had an incomplete pregnancy had a 17% decreased risk of ovarian cancer compared to those who had not (95% CI 0.78-0.87). Risk of ovarian cancer also decreased with increasing number of incomplete pregnancies (p-trend CONCLUSIONS: Incomplete pregnancies appear to be associated with a decreased risk of ovarian cancer, particularly for the clear cell histotype. Full births are more protective than incomplete pregnancies. However, these findings suggest that the hormonal milieu during pregnancies of short gestation may be sufficient to confer some protection against ovarian carcinogenesis. Citation Format: Alice W. Lee, Stacey Rosenzweig, Penelope Webb, Malcolm C. Pike, Celeste Leigh Pearce on behalf of the Ovarian Cancer Association Consortium.. FULL-TERM BIRTHS ARE PROTECTIVE FOR OVARIAN CANCER – WHAT ABOUT INCOMPLETE PREGNANCIES? [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr DP-009.