Dynamic tumor-infiltrating lymphocytes predicts survival in HR+/HER2− early breast cancer: a pre-to-post neoadjuvant chemotherapy study

INTRODUCTION: The prognostic implications of tumor-infiltrating lymphocytes (TILs) and their temporal changes (ΔTILs) during neoadjuvant chemotherapy (NAC) in hormone receptor-positive/ HER2-negative early breast cancer (HR+/HER2- eBC) remains clinically ambiguous. Our study investigates the association between TILs levels, longitudinal TILs evolution, and survival outcomes in a NAC-treated HR+/HER2- eBC cohort. METHODS: In this retrospective cohort analysis of 576 HR+/HER2- eBC patients (April 2011-December 2021), TILs were categorized as low (< 10%) or high (≥ 10%) using predefined thresholds. Multivariable Cox proportional hazards models evaluated invasive disease-free survival (iDFS) and overall survival (OS). ΔTILs patterns were analyzed in residual tumors. RESULTS: The cohort (median follow-up 68.1 months) comprised 393 TILs-low (68.2%) and 183 TILs-high (31.8%) tumors. Compared to TILs-low tumors, TILs-high tumors were associated with a higher Ki-67 index (≥ 20%) (P = 0.022), even though they were more frequently of smaller baseline size (< 3 cm) (P = 0.022). Elevated pre-NAC TILs independently predicted inferior iDFS (HR = 1.47, 95% CI 1.06-2.04, P = 0.021) and OS (HR = 1.64, 95% CI 1.11-2.43, P = 0.013). Post-NAC TILs escalation (low to high) conferred the worse prognosis versus sustained low TILs (iDFS: HR = 2.97, 95% CI 1.93-4.55, P < 0.001; OS: HR = 3.43, 95% CI 2.02-5.85, P < 0.001). Conversely, TILs reduction (high to low) correlated with improved survival over persistent high TILs (iDFS: HR = 0.51, 95% CI 0.30-0.86, P = 0.012; OS: HR = 0.54, 95%CI 0.31-0.96, P = 0.034). CONCLUSION: In HR+/HER2- eBC, elevated pre-treatment TILs are independently associated with inferior survival outcomes, while chemotherapy-induced TILs reduction in residual disease correlates with significant prognostic improvement.