In the FinHer dataset, 6 metagenes were associated with benefit from trastuzumab treatment; however, only the ANXA1 metagene remained significantly associated with trastuzumab response after multivariate adjustment (FDR=.03).

The FinHer data were from a phase 3 clinical trial that randomly assigned patients with HER2-positive breast cancer to receive chemotherapy plus trastuzumab or placebo.

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Stratification of the FinHer dataset according to expression level of ANXA1 demonstrated that low levels of ANXA1 expression was significantly associated with an 84% decrease in the risk of distant recurrence of breast cancer (hazard ratio [HR], 0.16; 95% CI: 0.05-0.5; P=0.002; FDR=.03).

In addition, high expression of ANXA1 was associated with recurrence (HR, 1.29; 95% CI: 0.55-3.02; P=0.56). Expression levels of other metagenes including Bcl-2, caspase-7, Chk2, DJ-1, and GATA3 were not predictive of response to trastuzumab.

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“Our finding that RPPA-based, gene expression metagenes predict lack of benefit to trastuzumab through ANXA1 raises new questions regarding the postoperative management of HER2-positive breast cancer,” the authors wrote.

“If confirmed by future prospective, randomized, controlled studies, this RPPA-based gene expression signature could be used to direct the rationale for adjuvant treatment and research in HER2-positive breast cancer.”


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