Effects of age and immune landscape on outcome in HER2-positive breast cancer in the NCCTG N9831 (Alliance) and NSABP B-31 (NRG) trials

Purpose: Young age has been shown to be an independent 0.68; P < 0.001; and age > 40; HR, 0.42; 95% CI, 0.33–0.54; P < predictor of poor outcome in breast cancer. In HER2-positive 0.001). Among patients who received chemotherapy alone, breast cancer, the effects of aging remain largely unknown. younger age was associated with poor outcome in the hor-Experimental Design: A total of 4,547 patients were mone receptor–positive subset, but not the hormone recep-included [3,132 from North Central Cancer Treatment tor–negative subset, in both trials. Although there was no Group (NCCTG) N9831 and 1,415 from National Surgical association between sTILs and age, a small, but significant Adjuvant Breast and Bowel Project (NSABP) B-31]. Patho-increase in mTIL CD45 and some immune subset signatures logic stromal tumor-infiltrating lymphocyte (sTIL) and were observed. Among patients who received chemotherapy molecular tumor infiltrating lymphocyte (mTIL) signatures alone, patients over 40 years of age with lymphocyte-predom-were evaluated. inant breast cancer had excellent outcome, with 95% remain-Results: In NCCTG N9831, comparable benefit of trastu-ing recurrence free at 15 years. zumab was observed in all patients [age 40; HR, 0.43; 95% Conclusions: Among patients treated with trastuzumab, confidence interval (CI), 0.28–0.66; P < 0.001; and age > 40; there was no significant difference in outcome related to age. HR, 0.56; 95% CI, 0.45–0.69; P < 0.001]. Similar results were Our study suggests that trastuzumab can negate the poor observed in NSABP B-31 (age 40; HR, 0.45; 95% CI, 0.29–prognosis associated with young age.