Previous research from the ShortHER trial established the prognostic value of tumor-infiltrating lymphocytes (TILs) in patients with early-stage HER2-positive breast cancer. This study investigates the influence of body mass index (BMI) on the prognostic impact of TILs. The ShortHER trial compared 9 weeks versus 1 year of adjuvant trastuzumab combined with chemotherapy in 1253 patients with HER2-positive early breast cancer. BMI data at baseline were available for 1213 patients (excluding 34 underweight individuals). Key outcomes included disease-free survival (DFS), recurrence-free survival (RFS), distant disease-free survival (DDFS), and overall survival (OS). Competing risk analysis was used to evaluate the cumulative incidence of different event types.
Among the patients, 583 (48%) were normal weight, 360 (29.7 percent) overweight, and 236 (19.5 percent) obese. Survival outcomes (DFS, RFS, DDFS, OS) were comparable between normal-weight patients and those with overweight or obesity. In the subgroup with both TIL and BMI data (n=819), higher TIL levels (per 5% increment) independently predicted better DFS (P=0.003), RFS (P=0.001), and DDFS (P=0.018) in normal-weight patients. In overweight or obese patients, higher TILs were linked only to improved DDFS (P=0.044). Normal-weight patients with TILs ≥20% showed significantly better DFS (P=0.007), RFS (P=0.002), and DDFS (P=0.027) than those with TILs <20%. No such differences were observed in overweight/obese patients. Competing risk analysis revealed higher rates of locoregional (P=0.001) and distant recurrence (trend, P=0.07) in normal-weight patients with low TILs, while overweight/obese patients with low TILs had increased distant recurrence (P=0.005). These findings indicate that elevated BMI may reduce the local protective benefits of TILs—while preserving their distant protective effects—in overweight or obese patients with HER2-positive early breast cancer receiving adjuvant chemotherapy and trastuzumab.
