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.
ASJC Scopus subject areas
- Cancer Research