Black Race Is Associated with a Worse Outcome in Patients with Hormone Receptor Positive, HER2-Normal Breast Cancer Treated with Adjuvant Chemohormonal Therapy.

Abstract

Abstract Background: Black race has been associated with worse outcome in operable breast cancer, which has been attributed to a higher incidence of “triple negative” (TN) disease, disparities in care, and comorbidities. We evaluated the effect of black race on outcomes by hormone receptor (HR) and HER2 expression in patients treated with standard adjuvant therapy in trial E1199 (N Eng J Med 2008; 358: 1663)Methods: This study included 4950 eligible women with axillary lymph node positive or high-risk node-negative breast cancer, all of whom received doxorubicin and taxane-containing chemotherapy, plus standard endocrine therapy if HR-positive (but not trastuzumab if HER2-positive). Endocrine therapy included tamoxifen alone (38%) or followed by an AI (57%), or an AI alone (5%). The effect of black race was evaluated using Cox's proportional hazards model method (1) as a single variable, (2) in a model that included race, phenotype (TN vs. HER2-pos vs. HR-pos, HER2-neg/unknown [HR+]) and their interaction, and (3) in a multivariate model considering age, tumor size, number of positive lymph nodes, body mass index (BMI), and treatment arm. The stepwise method was used for model selection. The endpoints evaluated included disease free survival (DFS) and overall survival (OS). Results are expressed as hazard ratios (HR), with a HR > 1 indicating a worse outcome for black race. All p-values are two sided.Results: Of 4950 eligible patients, 416 (8.4%) were black. Black race was associated with significantly higher rates of TN disease (34% vs. 19%; p<0.0001) and higher BMI (median 32.0 vs. 27.7, p<0.0001). Black race was also associated with inferior DFS (HR 1.35, p=0.002) and OS (HR 1.37, p=0.01) in the entire population. Black race was also associated with inferior DFS (HR 1.62, p=0.001) and OS (HR 1.59, p=0.03) in the HR+ group, but not in the TN or HER2-pos group. In a model including black race, phenotype, and their interaction, the interaction term for the HR+ group was significant for DFS (p=0.03) and demonstrated a strong trend for OS (p=0.08). In the multivariate model adjusted for other prognostic variables and BMI in the HR+ group, black race was significantly associated with inferior DFS (HR 1.82; 95% C.I. 1.36, 2.44, p<0.0001) and OS (HR 1.81; 95% C.I. 1.18, 2.78, p=0.007).Conclusions: We observed significantly inferior DFS and OS in black subjects who received chemohormonal therapy with HR+ disease (adjusted for other prognostic factors and BMI), but not in other phenotypes. This observation suggests that factors other than disparities in care or more advanced or aggressive disease may have contributed to recurrence. Potential explanations include poorer adherence to endocrine therapy, obesity and associated hyperinsulinemia, or other factors, which merit further investigation. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 37.