Higher tumour-infiltrating lymphocyte (TIL) levels are associated with improved survival outcomes in early ERBB2-positive breast cancer, supporting treatment de-escalation in select patients.
Patients with early-stage ERBB2-positive breast cancer often receive chemotherapy combined with trastuzumab, but there is increasing interest in identifying biomarkers that could help guide treatment de-escalation. The ShortHER trial in Italy examined the association between TIL levels and long-term survival outcomes in patients receiving either nine weeks or one year of trastuzumab alongside chemotherapy. This follow-up analysis, conducted at a median of nine years, assessed whether TIL levels could predict distant disease-free survival (DDFS) and overall survival (OS), potentially informing more tailored treatment approaches.
Of the 1,253 patients originally enrolled, 866 had evaluable TILs. Each 5% increase in TILs was linked to improved DDFS (hazard ratio [HR]: 0.87; 95% CI: 0.80–0.95; P=0.001) and OS (HR: 0.89; 95% CI: 0.81–0.98; P=0.01). Patients with TILs of 20% or higher had better 10-year OS rates (91.3%), which increased further for those with TILs of 30% or higher (93.3%) and 50% or higher (98.1%). The data also suggest that patients with lower TILs (<20%) benefited more from the longer trastuzumab regimen (10-year DDFS, 88.7% vs 81.0% for short treatment), whereas those with higher TILs (≥20%) had superior outcomes with the shorter regimen (10-year DDFS, 92.2% versus 87.1%; P for interaction =0.01). A similar trend was observed in OS rates, though not statistically significant (P for interaction =0.06).
This study provides the first evidence of an independent association between TILs and OS in ERBB2-positive early breast cancer, highlighting TILs as a potential biomarker for guiding treatment decisions. The findings suggest that patients with TILs of 20% or higher may not require the full year of trastuzumab and could safely receive a shorter course, reducing treatment burden and potential side effects.
Jenna Lorge, EMJ
Reference
Dieci MV et al. Tumor-infiltrating lymphocytes and survival outcomes in early ERBB2-positive breast cancer. JAMA Oncol. 2025;DOI:10.1001/jamaoncol.2024.6872.
