There is prevalence of estrogen-receptor α (ESR1) mutations in ER-positive aromatase inhibitor-treated metastatic breast cancer (MBC), according to a secondary analysis of the BOLERO-2 clinical trial in which patients were randomized to treatment with exemestane (25 mg oral daily) together with everolimus (10 mg oral daily) or with placebo. The study enrolled postmenopausal women with a diagnosis of MBC and prior exposure to an aromatase inhibitor. Researchers found:
- Of 541 evaluable patients, 156 (28.8%) had ESR1 mutation D538G (21.1%) and/or Y537S (13.3%), and 30 had both.
- These mutations were associated with shorter overall survival; wild-type, 32.1 months; D538G, 25.99 months; Y537S, 19.98; both mutations, 15.15 months.
- The D538G group (HR, 0.34) derived a similar progression-free survival benefit as wide type from addition of everolimus to exemestane.
Chandarlapaty S, Chen D, He W, et al. Prevalence of ESR1 mutations in cell-free DNA and outcomes in metastatic breast cancer. A secondary analysis of the BOLERO-2 Clinical Trial. [Published online ahead of print August 11, 2016]. JAMA Oncol. doi:10.1001/jamaoncol.2016.1279.