Body mass index and weight changes in patients with HER2-positive early breast cancer: A sub-analysis of the APHINITY trial

Background: Body mass index (BMI) may affect prognosis in patients with breast cancer (BC). We assessed the association of BMI and weight changes with outcomes of patients with HER2-positive early BC included in the APHINITY trial. Methods: This is an exploratory analysis of APHINITY (NCT01358877), randomized trial testing adjuvant dual vs. single HER2 blockade plus chemotherapy in HER2-positive early BC. BMI was collected at baseline and at two years after randomization. Patients were classified as underweight/normal weight (BMI<25 kg/m²) and overweight/obese (BMI≥25 kg/m²). The association of BMI with invasive disease-free survival (iDFS), distant recurrence-free interval (DRFI) and overall survival (OS) was investigated. Landmark approach was used to compare event for weight change ≥ 5.0 % at 2 years from baseline. Results: Of 4787 patients included, 2252 (47 %) were overweight/obese and 2535 (53 %) underweight/normal weight. Patients who were overweight/obese had more often chemotherapy discontinuation compared to underweight/normal weight patients (14 % vs. 9 %, p < 0.001). Patients who were overweight/obese exhibited worse iDFS (adjusted hazard ratio [aHR] 1.27; 95 % CI 1.06–1.52), DFRI (aHR 1.32; 95 % CI 1.06–1.64) and OS (aHR 1.38; 95 %CI 1.08–1.77) than underweight/normal weight patients. This effect on iDFS remained after adjusting for chemotherapy discontinuation (iDFS aHR 1.26, 95 % CI 1.05–1.51; DRFI aHR 1.31, 95 % CI 1.06–1.63; OS aHR 1.35 95 % CI 1.05–1.73). Weight changes at 2 years were not associated with clinical outcomes. Conclusions: Our exploratory findings suggest that overweight/obesity at diagnosis was associated with worse survival outcomes.