Abstract 3017: Breastfeeding and ovarian cancer risk by tumor immune profiles
Authors: Mongiovi Jennifer , Townsend Mary , Vitonis Allison , Babic Ana , Hecht Jonathan , Conejo-Garcia Jose , Fridley Brooke , Tworoger Shelley , Terry Kathryn , Sasamoto Naoko 
Published: April 2023

Abstract
Introduction: Breastfeeding is associated with decreased ovarian cancer risk, yet the biological mechanisms are not fully understood. We conducted an agnostic investigation of tumor immune profiles to better understand the role of the tumor microenvironment in the protective association between breastfeeding and ovarian cancer risk.
Methods: Multiplex immunofluorescence was used to measure the abundance of T cells and B cells in ovarian tumor samples on tissue microarrays from the Nurses’ Health Study (NHS; n=337), NHSII (n=127), and New England Case Control Study (NECC; n=214). We averaged the percent of cells within the tumor epithelium that were positive for the immune cell of interest across 3 cores per tumor and categorized tumors as having high or low immune cell abundance based on the median value across all tumors. Controls were non-cases and did not provide tissue samples (n=2,045). Self-reported history of breastfeeding was used to define ever/never and total duration of breastfeeding. Polytomous logistic regression models adjusted for age, birth cohort, race, parity, oral contraception use, and study, was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for breastfeeding and ovarian cancer risk by immune cell level.
Results: Overall, breastfeeding was associated with a reduced risk of tumors with low, but not high, subtypes of T cell abundance. Among parous women, history of ever breastfeeding decreased the risk of tumors with low helper T cells (CD3+CD4+; ORlow: 0.56, 95% CI: 0.41-0.77), but not high helper T cells (ORhigh: 0.85, 95% CI: 0.63-1.35; p-het=0.06). For total B cells (CD19+), having ever breastfed was associated with decreased risk of both low (ORlow: 0.64, 95% CI: 0.47-0.87) and high abundance in the tumor (ORhigh: 0.70, 95% CI: 0.62-0.96, p-het=0.67) among parous women. Similar results were observed for CD138+ plasma cells (ORlow:0.76, 95% CI: 0.56-0.99; ORhigh: 0.59, 95% CI: 0.37-0.94; p-het=0.34). Longer duration of breastfeeding was associated with decreased risk of developing tumors with low abundance of total B cells (CD19+, p-trend=0.02) and regulatory B cells (CD19+TNFR2+, p-trend=0.05), but not high abundance of CD19+ or CD19+TNFR2+ (p-het=0.01 and 0.03, respectively).
Conclusion: These results indicate that among parous women breastfeeding is associated with reduced risk of ovarian tumors with low infiltration of helper T cells while no heterogeneity was observed for risk by total B cells or plasma cells. Longer breastfeeding duration was associated with reduced risk of tumors low in regulatory B cells (CD19+TNFR+) with a dose-dependent response. Together, these results suggest breastfeeding may play a role in the activation of the tumor immune response. Further efforts are ongoing to disentangle the relationships between breastfeeding and parity with the tumor immune microenvironment.
Citation Format: Jennifer Mongiovi, Mary Townsend, Allison Vitonis, Ana Babic, Jonathan Hecht, Jose Conejo-Garcia, Brooke Fridley, Shelley Tworoger, Kathryn Terry, Naoko Sasamoto. Breastfeeding 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 3017.