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Elaine Mardis, from the Genome Institute at Washington University School of Medicine, on Sensitivity to Aromatase Inhibitors
Elaine R. Mardis, PhD, Professor of Genetics and Molecular Microbiology, co-director, the Genome Institute at Washington University School of Medicine, discusses a whole-genome analysis that looked for predictive markers of response to aromatase inhibitors in patients with estrogen-receptor-positive breast cancer.
The study examined biopsies from 77 patients in two neoadjuvant aromatase inhibitor trials. Overall, eighteen significantly mutated genes were implicated, including five genes (RUNX1, CBFB, MYH9, MLL3 and SF3B1) that previously were thought to be involved only in hematopoietic malignancies.
The trial found that patients with mutations in TP53 were more likely have high proliferation according to the marker Ki67, were classified as luminal B by gene expression profiling, and were less likely to respond to aromatase inhibitors. Inversely, mutations in a new gene, labeled MAP3K1, were associated with low proliferation, luminal A status, and commonly resulted in a response to aromatase inhibitors.
Overall, this study helps establish a possible set of predictive markers for the clinical efficacy of aromatase inhibitors in breast cancer.