Association of Tumor-Infiltrating Lymphocyte Subtypes with Clinical Characteristics and Prognosis in Young Women with Hormone Receptor–Positive Breast Cancer

PURPOSE: The role of tumor-infiltrating lymphocytes (TIL) remains unclear in hormone receptor (HR)-positive/HER2-negative breast cancer, particularly in young patients, whose immune microenvironment could be altered by age-related host and tumor differences. EXPERIMENTAL DESIGN: Patients with stage I to III HR-positive/HER2-negative tumors were identified from a prospective cohort study of patients with breast cancer diagnosed at age ≤40 years. Multiplexed immunofluorescence and semiautomated quantitative software measured cytotoxic T, non-CD8 T, T regulatory, exhausted T, and PDL1+ cells in stroma and tumor. Univariate analyses assessed differences in clinicopathologic characteristics by high versus low immune infiltration, divided based on median. TIL subtypes were evaluated as a continuous variable per 10% increase in Cox regression analyses for invasive breast cancer-free survival, distant disease-free survival (DDFS), and overall survival, adjusted for clinicopathologic parameters. RESULTS: Among 390 patients, high immune infiltration was associated with increasing age, Black race, grade 3 tumors, and metaplastic or micropapillary histologic subtypes. Over a median follow-up of 8 years, higher stromal and intratumoral non-CD8 T-cell infiltration, T regulatory-cell infiltration, and PDL1 expression were associated with improved invasive breast cancer-free survival. Higher intratumoral non-CD8 T-cell infiltration, T regulatory-cell infiltration, and PDL1 expression were associated with improved DDFS; higher stromal PDL1 expression was also associated with improved DDFS. Higher intratumoral cytotoxic T-cell infiltration and PDL1 expression were associated with improved overall survival. CONCLUSIONS: Characterization of immune subpopulations could help refine the prognostic value of TILs in young patients with HR-positive breast cancer, who may benefit from risk stratification for treatment individualization. See related commentary by Salgado and Kok, p. 2133.