Validation of the NSABP/NRG Oncology 8-gene trastuzumab-benefit signature in alliance/NCCTG N9831

Katherine L. Pogue-Geile, Nan Song, Daniel J. Serie, Ying Wang, Patrick G. Gavin, Rim S. Kim, Noriko Tanaka, Debora Fumagalli, Yusuke Taniyama, Zhuo Li, Priya Rastogi, Sandra M. Swain, Eleftherios P. Mamounas, Charles E. Geyer, Norman Wolmark, Peter C. Lucas, Soonmyung Paik, E. Aubrey Thompson

Research output: Contribution to journalArticle

Abstract

Our objective was to validate the NSABP 8-gene trastuzumab-benefit signature, developed and initially validated in NRG Oncology/NSABP B-31 in Alliance/NCCTG N9831. The B-31 and N9831 trials demonstrated the benefit of adding trastuzumab to chemotherapy in the adjuvant setting for HER2þ breast cancer patients. NSABP investigators utilized gene expression profiles of N9831 patients (N ¼ 892) to blindly assign patients to large-, moderate-, or no-trastuzumab benefit groups and then NCCTG investigators assessed the degree of trastuzumab benefit using Cox models adjusted for age, nodes, estrogen receptor/progesterone receptor status, tumor size, and grade. Hazard ratios and 2-sided P values for recurrence-free survival of the predicted large- (n ¼ 387), moderate- (n ¼ 401), and no-benefit (n ¼ 104) groups, based on the 8-gene signature were 0.47 (95% CI ¼ 0.31 to 0.73, P < .001), 0.60 (95% CI ¼ 0.39 to 0.92, P ¼ .02), and 1.54 (95% CI ¼ 0.59 to 4.02, P ¼ .38), respectively (Pinteraction ¼ .02), providing validation of the 8-gene signature in an independent study.

Original languageEnglish (US)
Article numberpkaa058
JournalJNCI Cancer Spectrum
Volume4
Issue number5
DOIs
StatePublished - 2020

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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