Obesity at diagnosis is associated with inferior outcomes in hormone receptor-positive operable breast cancer

Abstract

Background: Obesity has been associated with inferior outcomes in operable breast cancer, but the relation between body mass index (BMI) and outcomes by breast cancer subtype has not been previously evaluated.

Methods: The authors evaluated the relation between BMI and outcomes in 3 adjuvant trials coordinated by the Eastern Cooperative Oncology Group that included chemotherapy regimens with doxorubicin and cyclophosphamide, including E1199, E5188, and E3189. Results are expressed as hazard ratios (HRs) from Cox proportional hazards models (HR >1 indicates a worse outcome). All P values are 2-sided.

Results: When evaluated as a continuous variable in trial E1199, increasing BMI within the obese (BMI, ≥ 30 kg/m(2)) and overweight (BMI, 25-29.9 kg/m(2)) ranges was associated with inferior outcomes in hormone receptor-positive, human epidermal growth receptor 2 (HER-2)/neu-negative disease for disease-free survival (DFS; P = .0006) and overall survival (OS; P = .0007), but not in HER-2/neu-overexpressing or triple-negative disease. When evaluated as a categorical variable, obesity was associated with inferior DFS (HR, 1.24; 95% confidence interval [CI], 1.06-1.46; P = .0008) and OS (HR, 1.37; 95% CI, 1.13-1.67; P = .002) in hormone receptor-positive disease, but not other subtypes. In a model including obesity, disease subtype, and their interaction, the interaction term was significant for OS (P = .02) and showed a strong trend for DFS (P = .07). Similar results were found in 2 other trials (E5188, E3189).

Conclusions: In a clinical trial population that excluded patients with significant comorbidities, obesity was associated with inferior outcomes specifically in patients with hormone receptor-positive operable breast cancer treated with standard chemohormonal therapy.

Figure 1

Disease-free survival (DFS) and overall survival (OS), respectively, are shown for patients enrolled in the E1199 trial with (A, B) hormone receptor-positive (HR positive), human epidermal growth receptor 2 (HER-2)-negative/unknown disease, (C, D) triple-negative disease, and (E, F) HER-2–positive disease. HR, hazard ratio.

Figure 2

Relation between body mass index (BMI) and disease-free survival (DFS) and overall survival (OS), respectively, is shown for patients enrolled in the E1199 trial with hormone receptor-positive (HR+), human epidermal growth receptor 2-negative(HER2−)/unknown disease. HR, hazard ratio.