Effects of Age and Immune Landscape on Outcome in HER2-Positive Breast Cancer in the NCCTG N9831 (Alliance) and NSABP B-31 (NRG) Trials
Saranya Chumsri, Daniel J Serie, Zhuo Li, Katherine L Pogue-Geile, Aixa E Soyano-Muller, Afshin Mashadi-Hossein, Sarah Warren, Yanyan Lou, Gerardo Colon-Otero, Keith L Knutson, Edith A Perez, Alvaro Moreno-Aspitia, E Aubrey Thompson, Saranya Chumsri, Daniel J Serie, Zhuo Li, Katherine L Pogue-Geile, Aixa E Soyano-Muller, Afshin Mashadi-Hossein, Sarah Warren, Yanyan Lou, Gerardo Colon-Otero, Keith L Knutson, Edith A Perez, Alvaro Moreno-Aspitia, E Aubrey Thompson
Abstract
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; P < 0.001; and age > 40; HR, 0.56; 95% CI, 0.45-0.69; P < 0.001]. Similar results were observed in NSABP B-31 (age ≤ 40; HR, 0.45; 95% CI, 0.29-0.68; P < 0.001; and age > 40; HR, 0.42; 95% CI, 0.33-0.54; P < 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.
Trial registration: ClinicalTrials.gov NCT00005970 NCT00004067.
Conflict of interest statement
Conflict of interest: There is no relevant conflict of interest for Dr. Chumsri, Mr. Serie, Drs. Pogue-Geile, Soyano-Muller, Lou, Colon-Otero, Knutson, Moreno-Aspitia, and Thompson. Dr. Perez worked at Genentech, Inc. Mr. Mashadi-Hossein and Dr. Warren worked at NanoString Technologies, Inc.
©2019 American Association for Cancer Research.
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Source: PubMed