Background: We demonstrated the prognostic role of tumor-infiltrating lymphocytes (TILs) in patients with early human epidermal growth factor receptor 2 (HER2)-positive breast cancer (eBC) enrolled in the ShortHER trial. Here, we analyze how body mass index (BMI) modulates the prognostic role of TILs. Patients and methods: The ShortHER study randomized 1253 patients with HER2-positive eBC to 9 weeks versus 1 year of adjuvant trastuzumab + chemotherapy. We assessed BMI at diagnosis (available for n = 1213, n = 34 underweight were excluded). Survival endpoints were disease-free survival (DFS), recurrence-free survival (RFS), distant DFS (DDFS) and overall survival (OS). We calculated the cumulative incidence of first event types by competing risk analysis. Results: A total of 583 (48%) patients were lean, 360 (29.7%) overweight and 236 (19.5%) obese. Lean patients versus those with overweight or obesity had similar DFS, RFS, DDFS and OS. Within the TIL + BMI cohort (n = 819), TILs (5% increase) were independently associated with DFS (P = 0.003), RFS (P = 0.001) and DDFS (P = 0.018) in lean patients. In patients with overweight or obesity, TILs were independently associated only with DDFS (P = 0.044). In lean patients, TILs ≥20% were associated with improved DFS (P = 0.007), RFS (P = 0.002) and DDFS (P = 0.027) compared with TILs <20%. In patients with overweight or obesity, DFS, RFS, DDFS and OS did not significantly differ between TILs ≥20% and TILs <20%. In lean patients, there was a higher cumulative incidence of locoregional relapse (P = 0.001) and distant relapse (P = 0.07) in patients with TILs <20% versus TILs ≥20%. In patients with overweight or obesity, there was a higher cumulative incidence of distant relapse (P = 0.005) in patients with TILs <20% versus TILs ≥20%. Conclusions: We suggest that BMI may impair the local, but not distant, protective effect of TILs in patients with overweight or obesity with HER2-positive eBC treated with adjuvant chemotherapy + trastuzumab.
Interaction between tumor-infiltrating lymphocytes and BMI in early HER2-positive breast cancer: analysis of the ShortHER trial
Dieci, M V
;Miglietta, F;Guarneri, V
2025
Abstract
Background: We demonstrated the prognostic role of tumor-infiltrating lymphocytes (TILs) in patients with early human epidermal growth factor receptor 2 (HER2)-positive breast cancer (eBC) enrolled in the ShortHER trial. Here, we analyze how body mass index (BMI) modulates the prognostic role of TILs. Patients and methods: The ShortHER study randomized 1253 patients with HER2-positive eBC to 9 weeks versus 1 year of adjuvant trastuzumab + chemotherapy. We assessed BMI at diagnosis (available for n = 1213, n = 34 underweight were excluded). Survival endpoints were disease-free survival (DFS), recurrence-free survival (RFS), distant DFS (DDFS) and overall survival (OS). We calculated the cumulative incidence of first event types by competing risk analysis. Results: A total of 583 (48%) patients were lean, 360 (29.7%) overweight and 236 (19.5%) obese. Lean patients versus those with overweight or obesity had similar DFS, RFS, DDFS and OS. Within the TIL + BMI cohort (n = 819), TILs (5% increase) were independently associated with DFS (P = 0.003), RFS (P = 0.001) and DDFS (P = 0.018) in lean patients. In patients with overweight or obesity, TILs were independently associated only with DDFS (P = 0.044). In lean patients, TILs ≥20% were associated with improved DFS (P = 0.007), RFS (P = 0.002) and DDFS (P = 0.027) compared with TILs <20%. In patients with overweight or obesity, DFS, RFS, DDFS and OS did not significantly differ between TILs ≥20% and TILs <20%. In lean patients, there was a higher cumulative incidence of locoregional relapse (P = 0.001) and distant relapse (P = 0.07) in patients with TILs <20% versus TILs ≥20%. In patients with overweight or obesity, there was a higher cumulative incidence of distant relapse (P = 0.005) in patients with TILs <20% versus TILs ≥20%. Conclusions: We suggest that BMI may impair the local, but not distant, protective effect of TILs in patients with overweight or obesity with HER2-positive eBC treated with adjuvant chemotherapy + trastuzumab.
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