Post-Treatment Mutations in Estrogen Receptor Gene Linked to Breast Cancer Treatment Resistance

Researchers at the University of Michigan (U-M) Comprehensive Cancer Center, together with colleagues, have used DNA and RNA sequencing to identify a type of mutation that develops after breast cancer patients take anti-estrogen therapies. The mutations explain one reason why patients often become resistant to this therapy. The discovery stems from a program at the U-M Comprehensive Cancer Center called Mi-ONCOSEQ in which patients with advanced cancer have their DNA and RNA sequenced to identify all types of genetic mutations that could play a role in the cancer. Researchers use the findings to help direct therapies they think will work best. But they also use the data to find new genetic links. The detailed analysis means that researchers can identify anomalies among a small number of patients. In this study, they looked at 11 patients with metastatic breast cancer that was classified as estrogen-receptor-positive, meaning the cancer is influenced by the hormone estrogen. This is the most common type of breast cancer. The study was published online on November 3, 2013 in Nature Genetics. The analysis found that six patients had mutations in the estrogen receptor. All of them had been treated with an aromatase inhibitor, a type of drug that blocks estrogen production. What’s more, the researchers found that the mutations were not present before the patients started their treatment, which implied it was the therapy itself that caused the mutations to develop or be selected. “This is the tumor’s way of evading hormonal therapy. These mutations activate the estrogen receptor when there is no estrogen – as is the case when a patient takes an aromatase inhibitor.
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