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.”

References

  1. Sonnenblick A, Brohee S, Fumagalli D, et al. Integrative proteomic and gene expression analysis identify potential biomarkers for adjuvant trastuzumab resistance: analysis from the Fin-her phase III randomized trial. [published online ahead of print September 3, 2015]. Oncotarget. doi: 10.18632/oncotarget.5080.
  2. Lim LHK, Pervaiz S. Annexin 1, the new face of an old molecule. FASEB J. 2007;21(4):968-975.
  3. Ang EZ-F, Nguyen HT, Sim HL, et al. Annexin-1 regulates growth arrest induced by high levels of estrogen in MCF-7 breast cancer cells. Mol Cancer Res MCR. 2009;7(2):266-274.
  4. Shen D, Nooraie F, Elshimali Y, et al. Decreased expression of annexin A1 is correlated with breast cancer development and progression as determined by a tissue microarray analysis. Hum Pathol. 2006;37(12):1583-1591.

Topics:

Advanced Breast Cancer Breast Cancer