Abstract 1186: Contraception and ovarian cancer risk by tumor immune profiles
Authors: Mongiovi Jennifer , Babic Ana , Sasamoto Naoko , Townsend Mary , Vitonis Allison , Hecht Jonathan , Conejo-Garcia Jose , Fridley Brooke , Tworoger Shelley , Terry Kathryn 
Published: June 2023

Abstract
Introduction: An estimated 38 million US women currently use contraception, a critical component of women’s health. Yet, the impact of changing contraceptive types and patterns of use on ovarian cancer incidence is unclear and the biologic pathway through which contraception influences ovarian cancer risk is not well understood. Using multiplex immunofluorescence (mIF) technology, we evaluated how contraception influences the tumor immune microenvironment (e.g., T cells) to better understand the association of intrauterine device (IUD) and oral contraception (OC) use on ovarian cancer risk.
Methods: We measured tumor immune profiles via mIF on tissue microarrays including tumor cores from 214 women with ovarian cancer (85% high grade serous) and 414 population-based controls frequency matched on age who participated in the New England Case Control Study. T cell types were defined by expression of CD3+ (total T cells), CD3+CD4+ (helper), CD3+CD8+ (cytotoxic), CD3+CD4+FoxP3+ (regulatory), CD3+CD4+CD69+ or CD3+CD8+CD69+ (recently activated), or CD3+Tim3+ or CD3+Lag3+(exhausted). The average immune cell density across 3 cores per tumor was used to categorize tumors as high or low abundance based on the median across all tumors. Contraception use was self-reported and included having ever used an IUD and/or OCs and duration of use. Polytomous logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for ovarian cancer defined by tumor immune cell abundance adjusted for age at diagnosis or interview, parity, and family history of breast or ovarian cancer in first degree relative.
Results: Overall, ever use of IUD or OC was not differentially associated with ovarian cancer risk by T cell tumor immune profiles. However, for OC use of 5 years or longer, we observed a significant reduction in risk for low-abundance total T cell (ORlow=0.44, 95% CI 0.21-0.94), cytotoxic T cell (ORlow=0.44, 95% CI:0.21-0.94), regulatory T cell (ORlow=0.31, 95% CI: 0.14-0.68), and recently activated T cell (CD3+CD4+CD69+ ORlow=0.34, 95% CI: 0.17-0.68) tumors with significant trends with longer duration. There was no significant decrease in risk of tumors with high abundance of these T cell types, although statistically significant heterogeneity was only observed in the association for duration of OC use and risk by low and high abundance of recently activated helper T cells (CD3+CD4+CD69+, p-het=0.006).
Conclusion: These results suggest that ever use of IUD and OCs are not associated with risk of ovarian tumors by immune phenotype, though risk by T cell abundance may vary with longer duration. Analyses are ongoing and will be expanded to include types and patterns of contraception, other immune markers, and additional studies.
Citation Format: Jennifer Mongiovi, Ana Babic, Naoko Sasamoto, Mary Townsend, Allison Vitonis, Jonathan Hecht, Jose Conejo-Garcia, Brooke Fridley, Shelley Tworoger, Kathryn Terry. Contraception and ovarian cancer risk by tumor immune profiles [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1186.