Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer deaths in women. Compared to non- Hispanic white (NHW) women, African American (AA) women have much poorer survival after an EOC diagnosis, which, as we have found, may be in part due to AA women being less likely to receive standard-of- care therapy, and more likely to have chemotherapy dose reduction, even within an equal-access healthcare system. However, these factors do not completely explain survival disparities among AAs, and furthermore, little is known about other groups (e.g., Hispanics and Asians/Pacific Islanders (API)), although there is some evidence that Hispanic women also experience worse survival. Moreover, emerging evidence suggests racial differences in molecular subtype distribution. We propose to conduct the first integrative, cells-to-society evaluation of the interplay among multilevel factors on disparities in EOC treatment and survival outcomes. We will assemble a cohort of ~4,600 EOC cases, including ~280 AA, ~520 Hispanic, ~730 API, and ~2,980 NHW women diagnosed at Kaiser Permanente Northern California (KPNC) between 2000 and 2023. KPNC has longstanding electronic clinical databases, complete pathology specimen storage, long-term retention of members, and substantial variability in sociodemographic, clinical, and neighborhood characteristics among races/ethnicities. We will perform centralized pathology review to classify histotypes by the recent gold standard WHO criteria, and will conduct chart review to capture data that are not available electronically. We will examine determinants of racial/ethnic differences in treatment received, recurrence, and survival (overall and EOC-specific), including neighborhood social stressors through linkage to data on segregation, structural racism, ethnic enclaves, and geographic medical accessibility, health care system and patient-level factors. In 800 women (200 each of NHW, AA, Hispanic, and API) with high grade serous EOC, we will also characterize gene expression subtypes (to date studied almost exclusively in NHW women), to identify whether the relative distribution of aggressive subtypes contributes to the observed survival disparities. We will examine these factors in the context of both self-reported race/ethnicity and genetic ancestry. Our comprehensive integrative approach to examine the interplay among patient, health care, social contextual, and biological factors will provide unique insights into the persistent racial disparities in EOC survival. The KPNC setting provides the opportunity to examine these factors while minimizing confounding by the known contribution of insurance status, leveraging rich clinical databases to investigate and control for detailed prognostic variables, and avoiding survival bias. For EOC, this proposed study is unprecedented in its transdisciplinary nature, sample size, and multi-ethnic population, and will serve as a unique resource for future research related to multilevel factors to reduce EOC survival disparities.
Ovarian cancer is a deadly disease, but survival varies widely by race/ethnicity. We propose to examine whether differences in neighborhood characteristics, patient and clinical factors including receipt of recommended treatments, or molecular features of the tumors can account for these disparities, at least in part. Ovarian cancer is understudied in diverse populations, and the proposed work is one of the largest to search for potentially modifiable factors that can reduce disparities in survival.
