Prognostic impact of tumor-infiltrating lymphocytes in HER2+ metastatic breast cancer receiving first-line treatment

Breast cancer (BC) is a leading cause of death among women, with approximately 30% HER2−positive (HER2+). Although HER2-targeted therapies have improved outcomes for patients with HER2+ metastatic breast cancer (mBC), clinical challenges and prognostic variability remain. Tumor-infiltrating lymphocytes (TILs) have emerged as prognostic and predictive biomarkers in various tumors, including BC, but their role in HER2+ mBC is poorly understood. This multicentric retrospective cohort study evaluated the prognostic significance of TILs in 110 patients with HER2+ mBC treated with pertuzumab, trastuzumab, and taxane-based chemotherapy at two Italian institutes from June 2013 to May 2024. TILs were assessed on metastatic or primary tumor samples. High TILs levels (>5%) were independently associated with longer PFS and OS. TILs levels were higher in primary tumours than in metastases (p = 0.009), with significant variation by metastatic site. These findings underscore the potential of TILs as prognostic biomarkers in HER2+ mBC, necessitating further prospective studies.