Abstract C063: Risk of subsequent uterine or ovarian cancers in breast cancer survivors by cancer subtype and race-ethnicity

Abstract Introduction/Objectives: Breast cancer (BC) survivors face elevated risks of subsequent uterine (UC) and ovarian cancers (OC), but whether these risks differ by cancer subtypes is not clear. We evaluated whether BC subtypes defined by histology and hormone receptor status have a different risk of subsequent UC or OC overall and by cancer histology. Methods: Using SEER22 cancer registry data from 2000–2019, we estimated standardized incidence ratios (SIRs) for UC and OC among >1.6 million BC survivors aged ≥20 years. Analyses were stratified by BC histology, hormone receptor status (available only from 2010–2019), and subsequent cancer (UC/OC) histology. All cancer diagnoses were microscopically confirmed and excluded autopsy or death certificate diagnoses. Results: In this analysis, we included 10,645 eligible UC cases and 4,363 OC cases. Risks of UC and OC were elevated among BC survivors, with SIR of 1.3 (95% CI: 1.2-1.3) for both cancers, with the highest UC risk in Non-Hispanic (NH)-Asian/Pacific Islanders (PI) (SIR=1.9, 95% CI 1.8-2.1) and NH-Native American/Alaska Natives (NA/AN) (SIR=1.7, 1.2-2.4), and highest OC risk in NH-NA/AN (SIR=2.4, 1.5-3.6), Non-Hispanic (NH)-Asian/PI (SIR=1.7, 1.5-2.0) and Hispanic women (SIR=1.7, 1.6-1.9). Notably, the risk of more aggressive, non-endometrioid UC subtypes was substantially elevated overall (SIR=2.1, 2.0-2.2), particularly among survivors of invasive ductal carcinoma (SIR=2.2, 2.1-2.3) and those with triple-negative BC (SIR=2.1, 1.7-2.6). In contrast, the endometrioid UC subtype showed only slight elevation (Overall SIR=1.1, 1.0-1.1), with slightly increased risks among ER/PR+ (SIR=1.2, 1.2-1.3) and HER2- (SIR=1.2, 1.2-1.3) BC survivors. OC risk was primarily driven by the serous subtype (SIR=2.0, 2.0-2.1), with notably elevated risks among invasive ductal BC survivors (SIR=2.2, 2.1-2.3), those with ER-/PR- tumors (SIR=4.8, 4.2-5.5), and HER2- disease (SIR=3.1, 2.8-3.3). Triple-negative BC survivors had the highest risk for serous OC (SIR=5.7, 4.9-6.7). Conclusions: Our findings confirm that BC survivors have an increased risk of both UC and OC. The greatest risks are seen for aggressive subtypes such as non-endometrioid UC and serous OC, especially among triple-negative and invasive ductal BC survivors. The risk of subsequent UC and OC was highest among NH-API and NH-NA/AN. Further investigation is needed to clarify the potential role of confounding, treatment-related effects, and gaps in second cancer surveillance among BC survivors. Citation Format: Akemi T. Wijayabahu, Nicolas Wentzensen. Risk of subsequent uterine or ovarian cancers in breast cancer survivors by cancer subtype and race-ethnicity [abstract]. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr C063.