Gene Signature May Predict Breast Cancer Response to Aromatase Inhibitors

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(ChemotherapyAdvisor) – A multigene expression signature may predict response of breast cancer to aromatase inhibitors, according to a multi-institutional research team. The conclusion is based on a paper entitled “Whole-genome analysis informs breast cancer response to aromatase inhibition,” which was published in Nature online on June 12.

In this study, the investigators aimed “to correlate the variable clinical features of human estrogen-receptor-positive (HER-positive) breast cancer with somatic gene alterations.” Their approach was to use genomic approaches (massive parallel sequencing) and bioinformatic analysis to detect and interpret somatic gene changes in pretreatment tumor biopsies accrued from patients in two studies of neoadjuvant aromatase inhibitor therapy.

The investigators reported the identification of 18 significantly mutated genes. “Mutant MAP3K1 was associated with luminal A status, low-grade histology and low proliferation rates, whereas mutant TP53 was associated with the opposite pattern. Moreover, mutant GATA3 correlated with suppression of proliferation upon aromatase inhibitor treatment,” the investigators wrote. “Distinct phenotypes in HER-positive breast cancer are associated with specific patterns of somatic mutations that map into cellular pathways linked to tumor biology, but most recurrent mutations are relatively infrequent.”

This gene signature may predict a breast cancer response to aromatase inhibitors. However, the investigators concluded that “prospective clinical trials based on these findings will require comprehensive genome sequencing.”

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