A decade-long follow-up from the ShortHER randomised clinical trial suggests that tumour-infiltrating lymphocytes (TILs) could play a pivotal role in guiding treatment strategies for patients with early ERBB2 (formerly HER2)-positive breast cancer. The study highlights TILs as a potential biomarker for personalising adjuvant therapy, potentially allowing for safe de-escalation in specific patient groups.
The ShortHER trial, conducted across multiple centres in Italy, enrolled 1,253 patients between December 2007 and October 2013. Participants were randomised to receive either a standard one-year regimen or a shorter nine-week course of adjuvant trastuzumab, combined with chemotherapy. Tumour samples from 866 patients were analysed for TIL density, with outcomes assessed over a median follow-up of nine years.
The study revealed a significant association between higher TIL levels and improved survival outcomes. Each 5% increment in TILs corresponded to a 13% reduction in the risk of distant disease-free survival (DDFS) events (HR, 0.87; 95% CI, 0.80-0.95; P = .001) and an 11% reduction in the risk of death (HR, 0.89; 95% CI, 0.81-0.98; P = .01).
Notably, patients with TIL levels ≥20% demonstrated excellent survival rates, regardless of treatment duration. The 10-year overall survival (OS) rate was 91.3% for those with TILs ≥20%, 93.3% for TILs ≥30%, and 98.1% for TILs ≥50%. Conversely, patients with TILs <20% experienced better outcomes with the longer treatment regimen (10-year DDFS, 88.7% vs 81.0%).
This study provides, for the first time, evidence of an independent effect of TILs on OS in ERBB2-positive early breast cancer treated with adjuvant chemotherapy and trastuzumab. The findings suggest that patients with TILs ≥20% can undergo reduced trastuzumab duration and chemotherapy doses without an increased risk of distant relapse or death. This supports the integration of TILs into prognostic tools for more personalised treatment approaches.
While the study’s exploratory nature necessitates further validation, these results highlight the potential of TILs as a biomarker for treatment de-escalation. The ongoing research could pave the way for more targeted and less intensive treatment regimens, reducing the burden of therapy without compromising patient outcomes.
For detailed methodology and statistical analysis, refer to the full study published in JAMA Oncology.
Paper: Dieci, M-V., et al. Tumor-Infiltrating Lymphocytes and Survival Outcomes in Early ERBB2-Positive Breast Cancer: 10-Year Analysis of the ShortHER Randomized Clinical Trial. JAMA Oncology. February 13, 2025.
doi:10.1001/jamaoncol.2024.6872
