Stromal Tumor-infiltrating Lymphocytes in NRG Oncology/NSABP B-31 Adjuvant Trial for Early-stage HER2-positive Breast Cancer.

We retrospectively assessed association of stromal tumor-infiltrating lymphocytes (sTILs) with clinical outcomes and molecular variables reportedly predictive of trastuzumab-benefit in NSABP B-31 (N = 2,130). sTILs were assessed in 1,581 eligible B-31 cases utilizing all available H&E slides. Mean concordance between main reviewer and six other pathologists was 90.8% in 100 cases. Cox regressions were used to calculate hazard ratios (HRs). In chemotherapy and trastuzumab-added-to-chemotherapy arms, increases in sTILs, as a semi-continuous variable (combined arms HR = 0.42, 95% [CI]=0.27 to 0.64, two-sided P < 0.001) or as lymphocyte-predominant breast cancer (BC) with >50% sTILs (combined arms HR = 0.65, 95% CI = 0.49-0.86, two-sided P = 0.003), were statistically significantly associated with improved disease-free survival. There was no association of sTILs with trastuzumab-benefit. However, higher sTILs were statistically significantly associated with higher-trastuzumab-benefit groups by 8-gene prediction model (two-sided P < 0.001). Neither PIK3CA mutations nor Fc-gamma-receptor polymorphisms were associated with sTILs. sTILs may have utility as a prognostic biomarker identifying HER2-positive early-BC at low recurrence risk.