Risk stratification and relapse pattern in triple-negative breast cancer with pathological complete response after neoadjuvant treatment: the European GAMBIT real-world study.

Pathologic complete response after neoadjuvant treatment is considered a surrogate of cure in triple-negative breast cancer, yet around 10% of patients still relapse. Whether baseline stromal tumor-infiltrating lymphocytes can stratify this residual risk is unknown. Here, we report on GAMBIT, a multicentric real-world retrospective study of 2457 patients with triple-negative breast cancer or estrogen receptor-low disease, HER2-negative, of whom 1192 obtained a pathological complete response and 690 have evaluable tumor infiltrating lymphocytes. Among patients with pathological complete response, clinical nodal status and tumor infiltrating lymphocytes are independently prognostic and patients with clinical node-positive/low-tumor infiltrating lymphocytes tumors experience substantially worse outcomes, with five-year distant relapse-free survival of 83.4% and overall survival of 85.8%. In this high-risk subgroup, five-year cumulative incidence of central nervous system reaches 7.5%, including 6.9% presenting as isolated central nervous system relapse. In this work, we identify a high-risk subgroup despite pathologic complete response and provide a framework supporting risk-adapted trial design incorporating central nervous system-directed strategies.