what is known already: Shared molecular alterations and candidate precursor lesions suggest that tumor histology and grade may be used to classify ovarian tumors into likely etiologic pathways.design: This case -control study included 1571 women diagnosed with invasive EOC and 2100 population-based controls that were enrolled from 1992 to 2008. Reproductive risk factors as well as other putative risk factors for ovarian cancer were assessed through in-person interviews.participants/materials, setting, methods: Eligible cases were diagnosed with incident ovarian cancer, were aged 18 and above and resided in eastern Massachusetts or New Hampshire, USA. Controls were identified through random digit dialing, drivers' license and town resident lists and were frequency matched with the cases based on age and study center.main results and the role of chance: We used polytomous logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for type I/II EOC or using a pathway-based grouping of histologic subtypes. In multivariate analyses, we observed that having a history of endometriosis (OR ¼ 1.92, 95% CI: 1.36 -2.71) increased the risk for a type I tumor. Factors that were strongly inversely associated with risk for a type I tumor included parity (≥3 versus 0 children, OR ¼ 0.15, 95% CI: 0.11 -0.21), having a previous tubal ligation (OR ¼ 0.40, 95% CI: 0.26-0.60) and more weakly hysterectomy (OR ¼ 0.71, 95% CI: 0.45-1.13). In analyses of histologic pathways, parity (≥3 versus 0 children, OR ¼ 0.13, 95% CI: 0.10 -0.18) and having a previous tubal ligation (OR ¼ 0.41, 95% CI: 0.28-0.60) or hysterectomy (OR ¼ 0.54, 95% CI: 0.34-0.86) were inversely associated with risk of endometrioid/clear cell tumors. Having a history of endometriosis strongly increased the risk for endometrioid/clear cell tumors (OR ¼ 2.41, 95% CI: 1.78 -3.26). We did not observe significant differences in the risk associations across these tumor classifications for age at menarche, menstrual cycle length or infertility.limitations, reasons for caution: A potential limitation of this study is that dividing the cases into subgroups may limit the power of these analyses, particularly for the less common tumor types. Since cases were enrolled after their diagnosis, it is possible that the most aggressive cases were not included in the study.wider implications of the findings: This study provides insights about the role of reproductive factors in relation to risk of pathway-based subgroups of ovarian cancer that with further confirmation may assist with the development of improved strategies for the prevention of these different tumor types.

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Ovarian cancer is the fifth leading cause of cancer death for women in the U.S. and the 7th most fatal worldwide. Reproductive and hormonal exposures are known to influence risk of ovarian cancer. We therefore investigated whether these exposures also influence ovarian cancer survival. We studied survival in relation to hormonal and reproductive history in invasive epithelial ovarian cancer cases and controls from the New England based Case-Control Studies (NECC, 1,642 cases and 2,100 controls). Cases and controls were identified between 1992 and 2008 in New Hampshire and eastern Massachusetts. At the time of enrollment, participants were interviewed in person on a wide range of known and suspected risk factors, including hormone use, childbearing, lifestyle habits and anthropometric characteristics. Polytomous logistic regression was applied to evaluate whether a risk factor was associated differently with fatal (those that died within 3 years of diagnosis) versus non-fatal cases while controlling for other covariates and P-values for heterogeneity (comparing the Odds Ratios (ORs) for fatal ovarian cancer to the ORs for non-fatal ovarian cancer) were calculated based on the maximum likelihood estimates. A total of 360 of the 1642 women with ovarian cancer (22%) died within 3 years. We found that fatal ovarian cancer was associated with increasing age (multivariate OR 1.05 per 1 year increase in age, 95% CI 1.04 − 1.07, P-value < 0.0001), post-menopausal status (multivariate OR 1.31 vs pre-/dubious menopause, 95% CI 0.97 − 1.77, P-value < 0.0001) and oral contraceptive pill use was consistently more protective across all duration of use categories (P-value = 0.01) as compared with the non-fatal cases. Associations with tubal ligation, total number of ovulatory years, body mass index and family history of breast/ ovarian cancer did not differ significantly between fatal and non-fatal ovarian cancer cases. These results suggest that the most aggressive subset of invasive epithelial ovarian cancer exhibits important differences in its reproductive and hormonal risk factor profile as compared with non-fatal cases, and that selected protective factors such as oral contraceptive pill use may be especially important for the prevention of the most aggressive subgroup of disease. Citation Information: Cancer Prev Res 2011;4(10 Suppl):A108.