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 predictor of poor outcome in breast cancer. In HER2-positive breast cancer, the effects of aging remain largely unknown.

Experimental Design: A total of 4,547 patients were included [3,132 from North Central Cancer Treatment Group (NCCTG) N9831 and 1,415 from National Surgical Adjuvant Breast and Bowel Project (NSABP) B-31]. Pathologic stromal tumor-infiltrating lymphocyte (sTIL) and molecular tumor infiltrating lymphocyte (mTIL) signatures were evaluated.

Results: In NCCTG N9831, comparable benefit of trastuzumab was observed in all patients [age ≤ 40; HR, 0.43; 95% confidence interval (CI), 0.28-0.66; < 0.001; and age > 40; HR, 0.56; 95% CI, 0.45-0.69; < 0.001]. Similar results were observed in NSABP B-31 (age ≤ 40; HR, 0.45; 95% CI, 0.29-0.68; < 0.001; and age > 40; HR, 0.42; 95% CI, 0.33-0.54; < 0.001). Among patients who received chemotherapy alone, younger age was associated with poor outcome in the hormone receptor-positive subset, but not the hormone receptor-negative subset, in both trials. Although there was no association between sTILs and age, a small, but significant increase in mTIL CD45 and some immune subset signatures were observed. Among patients who received chemotherapy alone, patients over 40 years of age with lymphocyte-predominant breast cancer had excellent outcome, with 95% remaining recurrence free at 15 years.

Conclusions: Among patients treated with trastuzumab, there was no significant difference in outcome related to age. Our study suggests that trastuzumab can negate the poor prognosis associated with young age.