Different Mutations May Predict Different Responses to Chemotherapy

Among patients with estrogen receptor (ER)-positive, metastatic breast cancer, those who had a D538G and/or a Y537S mutation in the estrogen receptor 1 (ESR1) gene, as detected in cell-free DNA obtained from patient blood samples, had significantly worse median overall survival.

Results from clinical trial showed that adding everolimus to the standard hormonal therapy exemestane improved outcomes for postmenopausal women with ER-positive, locally advanced or metastatic breast cancer that has progressed after treatment with an aromatase inhibitor.


Scientists at the Memorial Sloan Kettering Cancer Center (New York, NY, USA) evaluated blood samples from 541 of the 724 patients enrolled in BOLERO-2 clinical trial. They detected the D538G ESR1 mutation in samples from 83 patients, the Y537S ESR1 mutation in samples from 42 patients, and both mutations in samples from 30 patients.

Median overall survival was 32.1 months for patients with neither a D538G nor the Y537S ESR1 mutation, 26 months for those with only a D538G mutation, 20 months for those with only a Y537S mutation, and 15.2 months for those with both mutations. Exploratory analyses showed that adding everolimus to exemestane more than doubled progression-free survival for patients with neither ESR1 mutation and for those with a D538G mutation. However, the treatment combination did not appear to increase progression-free survival for patients with a Y537S mutation.

Sarat Chandarlapaty, MD, PhD, a medical oncologist, said, “Using a simple blood test, we found that the D538G and Y537S mutations in the estrogen receptor are more common in patients with advanced, ER-positive breast cancer than previously appreciated and that patients with these mutations don't respond as well to currently used therapies and die from their disease sooner than patients who do not have these mutations.” The study was presented on December 10, 2015, at the San Antonio Breast Cancer Symposium held in San Antonio (TX, USA).

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Memorial Sloan Kettering Cancer Center