The relationship between quantitative human epidermal growth factor receptor 2 gene expression by the 21-gene reverse transcriptase polymerase chain reaction assay and adjuvant trastuzumab benefit in Alliance N9831

摘要

IntroductionThe N9831 trial demonstrated the efficacy of adjuvant trastuzumab for patients with human epidermal growth factor receptor 2 (HER2) locally positive tumors by protein or gene analysis. We used the 21-gene assay to examine the association of quantitative HER2 messenger RNA (mRNA) gene expression and benefit from trastuzumab.MethodsN9831 tested the addition of trastuzumab to chemotherapy in stage I–III HER2-positive breast cancer. For two of the arms of the trial, doxorubicin and cyclophosphamide followed by paclitaxel (AC-T) and doxorubicin and cyclophosphamide followed by paclitaxel and trastuzumab concurrent chemotherapy-trastuzumab (AC-TH), recurrence score (RS) and HER2 mRNA expression were determined by the 21-gene assay (Oncotype DX?) (negative 10?% positive cells?=?positive), 91?% for RT-PCR versus central fluorescence in situ hybridization (FISH) (≥2.0?=?positive) and 94?% for central IHC versus central FISH. In the primary analysis, the association of HER2 expression by 21-gene assay with trastuzumab benefit was marginally nonsignificant (nonlinear p?=?0.057). In hormone receptor-positive patients (local IHC) the association was significant (p?=?0.002). The association was nonlinear with the greatest estimated benefit at lower and higher HER2 expression levels.ConclusionsConcordance among HER2 assessments by central IHC, FISH, and RT-PCR were similar and high. Association of HER2 mRNA expression with trastuzumab benefit as measured by time to distant recurrence was nonsignificant. A consistent benefit of trastuzumab irrespective of mHER2 levels was observed in patients with either IHC-positive or FISH-positive tumors. Trend for benefit was observed also for the small groups of patients with negative results by any or all of the central assays.Trial registrationClinicaltrials.gov NCT00005970. Registered 5 July 2000.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-015-0643-7) contains supplementary material, which is available to authorized users.