Abstract PO-219: The implications of genetic ancestry and allostatic load on clinical outcomes in the ECOG-ACRIN adjuvant breast cancer trial E5103
Authors: Obeng-Gyasi Samilia , ONeill Anne , Miller Kathy D. , Schneider Bryan P. , Patridge Ann H. , Timsina Lava R. , Sledge George W. , Wagner Lynne , Carlos Ruth C. 
Published: January 2022

Abstract
Introduction: Elevated allostatic load (AL) has been associated with poor tumor prognostic features in Black breast cancer patients and worse disease specific and overall survival among cancer patients. To date, there are no studies evaluating the relationship between genetic ancestry, allostatic load and clinical trial endpoints such as completion of chemotherapy per protocol or overall survival. Prior evaluations of the ECOG-ACRIN adjuvant breast cancer trial E5103 suggests African ancestry is associated with a worse invasive disease-free survival and lower odds of chemotherapy completion. The objective of this study is to evaluate the association of genetic ancestry and AL with trial completion per protocol and with overall survival among patients in E5103. Methods: ECOG-ACRIN E5103 was a clinical trial that compared doxorubicin and cyclophosphamide (AC) for four cycles, followed by 12 weeks of weekly paclitaxel with placebo (Arm A) to the same chemotherapy with either concurrent bevacizumab (Arm B) or with concurrent plus sequential bevacizumab (Arm C) among women with node positive or high-risk node negative HER2 negative disease. Genetic ancestry groups of African ancestry (AA), European ancestry (EA) and other ancestry (OA) were determined using genome-wide single nucleotide polymorphisms. AL, at trial entry, was comprised of the biomarkers body mass index, systolic blood pressure, diastolic blood pressure, creatinine, IL6, IL10, and TNF alpha. To calculate AL, patients were awarded a point if their biomarker value was above the 75 percentile of the study sample. Logistic regression and Cox-Proportional Hazard models (odds ratio(OR) and hazard ratio (HR) estimates with corresponding 95% confidence intervals (CI)) were used to assess association with chemotherapy completion and with overall mortality. Estimates for AL were adjusted for genetic ancestry. Results: There were 348 patients in the study. The majority of the sample was of EA (EA 80%, AA 10%, OA 10%). Median (range) of AL was 2(0-6). Patients of AA (2.1(1.3)) and EA (1.88(1.4)) had a higher mean (SD) AL score compared to OA patients (0.91(1.1). On adjusted analysis, a 1 unit increased in AL was associated with a 15% reduction in the odds of completing chemotherapy per protocol (OR 0.85, 95% CI 0.72-0.99). Additionally, a 1 unit increase in AL was associated with a 14% increase in the hazard of death (HR 1.14, 95%CI 1.02-1.29). There was no association between ancestry and chemotherapy completion (AA OR 0.95, 95%CI 0.47-1.93; OA 1.82, 95%CI 0.78-4.23; ref EA) or survival (AA HR 1.40, 95% CI 0.85-2.31), OA 0.89 (0.46-1.73; ref EA). Moreover, there was no interaction between AL and ancestry. Conclusion: Among patients enrolled in E5103, AL appeared to be a better predictor of chemotherapy completion and overall survival than genetic ancestry. These results suggest life course exposure to chronic stress has implication in clinical outcomes even within the context of equivalent access to and quality of care.
Citation Format: Samilia Obeng-Gyasi, Anne ONeill, Kathy D. Miller, Bryan P. Schneider, Ann H. Patridge, Lava R. Timsina, George W. Sledge, Lynne Wagner, Ruth C. Carlos. The implications of genetic ancestry and allostatic load on clinical outcomes in the ECOG-ACRIN adjuvant breast cancer trial E5103 [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-219.