Abstract PO3-27-05: Racioethnic and Ancestral Differences in Risk of Cardiometabolic Conditions and Cardiovascular Disease in Women Treated for Breast Cancer: the Pathways Heart Study

Abstract Background: Despite the established literature of racioethnic disparities in cardiovascular disease (CVD) in the general population, few studies have examined such differences in women after BC treatment, who are at higher risk due to cardiotoxic cancer treatment. Moreover, few prior studies have considered genetic similarity among the participants in the analyses, which can be objectively inferred to delineate the ancestral background of an individual. Methods: The Pathways Heart Study was established to investigate the incidence of cardiometabolic risk factors and CVD events in women with a history of BC at Kaiser Permanente Northern California (KPNC). The main study endpoints for this analysis were cardiometabolic risk factors (hypertension, diabetes, and dyslipidemia) and CVD events, identified by ICD and CPT codes from EHR. Prevalent conditions were identified within 3 years prior to the date of BC diagnosis, and incident conditions were from the date of BC diagnosis to December 31, 2021. Ethnicity was self-reported and classified as non-Hispanic White (NHW), non-Hispanic Black (NHB), Asian, Hispanic, other, or unknown. Global genetic ancestry was estimated to capture the proportion of continental ancestries genetically similar to the reference populations in Africa, Americas, Asia, and Europe from the 1000 Genome Project and Human Genome Diversity Project (HGDP), which, with the current lack of universally accepted labeling, are herein referred to as African, Native American, Asian, and European ancestry, respectively. Multivariable logistic and Cox proportional hazards regression models with all-cause mortality considered as competing risk were used to analyze the associations of race and ethnicity and genetic similarity with prevalent and incident cardiometabolic risk factors and CVD events. Results: Of the 4,071 women with BC in this analysis, 2,713 (66.6%) self-reported as NHW, 305 (7.5%) as NHB, 512 (12.6) as Asian, 447 (11.0%) as Hispanic, and 94 (2.3%) as other or unknown. NHB, Asian, and Hispanic women were more like to have prevalent diabetes than NHW women, the pattern of which persisted after BC diagnosis. Adjusted OR (95% CI) of risk of incident diabetes was 1.74 (1.21-2.49) for NHB, 3.63 (2.59-5.08) for Asian, and 2.19 (1.58-3.04) for Hispanic women, as compared to NHW. Analysis of genetic similarity revealed results consistent with self-reported race and ethnicity (sHR [95% CI] per 25% increment of African ancestry 1.19 [1.07-1.34], Asian ancestry 1.57 [1.44-1.72], and Native American ancestry 1.60 [1.29-2.00]), in comparison to European ancestry. For CVD risk, NHB women were more like to develop any prevalent and incident CVD than NHW women, particularly for ischemic heart disease (incident risk sHR=1.80 [1.10-2.94]). Genetic similarity analyses also showed higher risk of ischemic heart disease associated with African ancestry (incident risk per 25% increment, sHR=1.23 [1.06-1.43]). In contrast, Hispanic women were at lower risk of any incident CVD, serious CVD, arrhythmia, heart failure or cardiomyopathy, and ischemic heart disease. Similarly, lower risk of these CVD conditions was associated with Native American ancestry. Conclusions: Compared with women who self-reported as NHW, those self-reported as NHB, Asian, and Hispanic were at higher risk of diabetes prior to BC diagnosis and the elevated risk persisted after BC diagnosis. Moreover, Black women had higher risk of prevalent and incident CVD, whereas Hispanic women had lower risk of CVD, the latter of which might be related to the admixture of Native American ancestry. To our knowledge, this is the largest multi-ethnic study of disparities in CVD health in women post BC treatment, demonstrating corroborating findings between self-reported race and ethnicity and genetic similarity. The results highlight disparities in cardiometabolic risk factors and CVD among BC survivors that may warrant more research and clinical attentions. Citation Format: Song Yao, Haiyang Sheng, Peter Fiorica, Richard Cheng, Lucas Mendicino, Angela Omilian, Qianqian Zhu, Janise Roh, Cecile Laurant, Valerie Lee, Isaac Ergas, Carlos Iribarren, Jamal Rana, Mai Nguyen-Huynh, Eileen Rillamas-Sun, Dawn Hershman, Christine Ambrosone, Lawrence Kushi, Heather Greenlee, Marilyn Kwan. Racioethnic and Ancestral Differences in Risk of Cardiometabolic Conditions and Cardiovascular Disease in Women Treated for Breast Cancer: the Pathways Heart Study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-27-05.