Purpose: Both African American (AA) race and obesity are associated with worse survival in early stage breast cancer. Obesity disproportionately affects AA women, and may further racial disparities in breast cancer. Prior work investigating the intersection of race, BMI, and outcome in the large adjuvant trial E1199 found obesity to be prognostic of worse survival in White patients, with no significant impact on the disparately inferior survival outcomes seen in Black patients. However, this analysis was based on self-reported race, which neglects underlying genetic ancestry that may drive biologic differences. Here, we investigate the impact of BMI on outcomes in patients of African or European ancestry in the phase III adjuvant breast cancer trial E5103. Methods: E5103 enrolled patients with high risk, HER2 negative, early stage breast cancer to receive adjuvant doxorubicin and cyclophosphamide for 4 cycles, followed by 12 weeks of weekly paclitaxel, with or without bevacizumab. Genetic ancestry was determined on the 3,373 patients with available germline DNA, BMI, and outcome data using principal components from a genome-wide array. The primary objective was to assess the impact of BMI on disease free survival (DFS) and overall survival (OS) by ancestry. A univariate Cox proportional hazard model was used to evaluate the correlation between continuous or binary BMI and survival in AA or European Americans (EA). Results: 11.6% (n=390) of patients were genetically classified as AA and 74.6% (n=2517) as EA. Higher BMI (increment of every 5 kg/m2) was significantly associated with worse DFS (HR=1.24, p=0.006) and OS (HR=1.38, p=0.005) only in AAs, but not in EAs (DFS p=0.76, OS p=0.35). Exploring BMI categories in AAs, survival differences were most significant between patients who had morbid obesity (BMI ≥40) and those who did not (DFS HR= 2.01, p=0.009; OS HR=2.19, p=0.045). However, in EAs, even morbid obesity was not associated with survival (DFS p=0.89, OS p=0.31). In the ER+ sub-population, BMI was associated with both DFS (HR=1.29, p=0.032) and OS (HR=1.60, p=0.017) in AAs, but only with OS in EAs (HR=1.15, p=0.049). In the triple negative sub-population, there was a trend toward worse survival with increasing BMI in AAs (p=0.098), but not in EAs (p=0.62). Conclusion: In contrast to prior work based on self-reported race, we found BMI to be significantly associated with worse survival in women of African ancestry in E5103, a large adjuvant trial that reflects our current approach to curative systemic therapy in breast cancer. Categorically, this association was significant only for morbid obesity, suggesting the relationship between BMI, race, and outcome may depend on the degree of obesity. Genetic ancestry may explain biologic differences driving both higher BMI and worse outcomes resulting in racial disparities in breast cancer.

Citation Format: Tarah J. Ballinger, Guanglong Jiang, Fei Shen, Kathy D. Miller, Bryan P. Schneider. Impact of African ancestry on the relationship between body mass index (BMI) and survival in early stage breast cancer: Retrospective analysis from E5103 [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-172.