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Effects of Age and Immune Landscape on Outcome in HER2-Positive Breast Cancer in the NCCTG N9831 (Alliance) and NSABP B-31 (NRG) Trials.

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.

SUBMITTER: Chumsri S

PROVIDER: S-EPMC6634998 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Effects of Age and Immune Landscape on Outcome in HER2-Positive Breast Cancer in the NCCTG N9831 (Alliance) and NSABP B-31 (NRG) Trials.

Chumsri Saranya S Serie Daniel J DJ Li Zhuo Z Pogue-Geile Katherine L KL Soyano-Muller Aixa E AE Mashadi-Hossein Afshin A Warren Sarah S Lou Yanyan Y Colon-Otero Gerardo G Knutson Keith L KL Perez Edith A EA Moreno-Aspitia Alvaro A Thompson E Aubrey EA

Clinical cancer research : an official journal of the American Association for Cancer Research 20190226 14

<h4>Purpose</h4>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.<h4>Experimental design</h4>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 ...[more]

PMID: 30808774

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Project description:Purpose: Recent trials have shown potential benefit of extended adjuvant endocrine therapy and relatively high risk of recurrence (RoR) after 5 years in hormone receptor-positive (HR+) human epidermal growth factor receptor 2-negative (HER2-) breast cancer. Although risk of late relapse in HR+ HER2- breast cancer is fairly well defined, the risk in HER2-positive (HER2+) breast cancer treated with adjuvant trastuzumab-based chemotherapy remains largely unknown.Methods: We included 3,177 patients with HER2+ breast cancer treated with adjuvant chemotherapy alone or with trastuzumab from the North Central Cancer Treatment Group N9831 (ClinicalTrials.gov identifier: NCT00005970) and National Surgical Adjuvant Breast and Bowel Project B-31 (ClinicalTrials.gov identifier: NCT00004067) trials.Results: Overall, HR+ breast cancer was significantly associated with improved recurrence-free survival (RFS) during the first 5 years (hazard ratio, 0.65; 95% CI, 0.56 to 0.77; P < .001). Among patients treated with trastuzumab, cumulative hazard for RFS was lower in patients with HR+ HER2+ breast cancer during the first 5 years (10.96% v 17.48%; hazard ratio, 0.60; 95% CI, 0.45 to 0.79; P < .001). However, there was no significant difference in RFS based on HR status during years 5 to 10 (hazard ratio, 1.32; 95% CI, 0.93 to 1.88; P = .12). A comparable degree of trastuzumab benefit was observed in HR+ and HR- breast cancers ( P for interaction = .87). Furthermore, we observed low RoR in years 5 to 10 among patients with HR+ HER2+ breast cancer: 3.23% in patients without lymph node involvement (N0) and 6.39% in patients with involvement of one to three lymph nodes (N1).Conclusion: The benefit of adjuvant trastuzumab persists for a long time. A distinct pattern of recurrence was observed between HR+ and HR- HER2+ disease but with similar degree of benefit from adjuvant trastuzumab. RoR in years 5 to 10 in HR+ HER2+ breast cancer is low, particularly in patients with N0 or N1 disease.

Dataset Information

Effects of Age and Immune Landscape on Outcome in HER2-Positive Breast Cancer in the NCCTG N9831 (Alliance) and NSABP B-31 (NRG) Trials.

Publications

Effects of Age and Immune Landscape on Outcome in HER2-Positive Breast Cancer in the NCCTG N9831 (Alliance) and NSABP B-31 (NRG) Trials.

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