ER-positivity, ESR1 Gene Levels Linked With Less Trastuzumab Benefit

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ER-positivity and higher ESR1 gene levels may benefit less from adjuvant trastuzumab after chemotherapy.
ER-positivity and higher ESR1 gene levels may benefit less from adjuvant trastuzumab after chemotherapy.

Patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancers that are estrogen receptor (ER)-positive and have low HER2 fluorescence in situ hybridization (FISH) ratio, or those with higher ESR1 gene levels may benefit less from adjuvant trastuzumab after chemotherapy.1

Researchers led by Sherene Loi, MD, PhD, of the Peter MacCallum Cancer Centre in Australia conducted a secondary analysis of 5009 patients with early stage HER2-positive breast cancer from the international, multicenter, randomized HERceptin Adjuvant (HERA) trial.

In one cohort, 3037 patients were randomized to receive either no trastuzumab or 1 or 2 years of trastuzumab after adjuvant chemotherapy. The second cohort consisted of 615 patients whose transcript levels of ESR1 and HER2 genes were available. Primary and secondary endpoints were disease-free survival and overall survival, respectively, in the intent-to-treat population. Median follow-up time was 8 years among all patients.

In the first cohort, patients in all status levels of ER, IHC, and FISH except those who were ER-positive or who had a low HER2:FISH ratio were found to have a significant treatment effect on disease-free and overall survival.

In addition, there was a significant predictive effect of the ESR1 gene in both disease-free and overall survival in the second cohort, indicating that breast cancers with higher ESR1 levels may also derive less of a benefit from trastuzumab.

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“These data may explain heterogeneity in response to anti-HER2 agents in HER2-positive, ER-positive breast cancers as some may be more luminal-like than HER2-driven,” the authors concluded.

Reference

  1. Loi S, Dafni U, Karlis D, et al. Effects of estrogen receptor and human epidermal growth factor receptor-2 levels on the efficacy of trastuzumab: a secondary analysis of the HERA trial [published online ahead of print April 21, 2016.] JAMA Oncol. doi: 10.1001/jamaoncol.2016.0339.

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