ESR1 mutations detected by circulating tumor (ct) DNA analysis may predict clinical progression among patients being treated with aromatase inhibitors (AIs) for estrogen receptor–positive breast cancer, according to a study published in the Annals of Oncology.1

Resistance mutation–analysis is used to predict clinical progression in several disease states, including EGFR­-positive lung cancer and KRAS­-mutant colorectal cancer. For this study, researchers analyzed ctDNA samples from patients with estrogen receptor–positive breast cancer to determine mechanisms of evolved resistance to AI therapy.

ctDNA samples were collected and analyzed every 3 months from 83 patients receiving AI therapy in the first line. ESR1 mutations were detected in 56.4% (22) of the 39 patients who progressed on first-line therapy; in 19 of these 22 patients, ESR1 mutations were detectable a median of 6.7 months prior to disease progression. ESR1 mutations were also detected in 5 of the 33 patients without clinical progression.

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KRAS mutations were detected in about 20% of other evaluated samples, though there was no significant association between KRAS status and overall or progression-free survival.

The authors concluded that “AI resistant cancers are genetically heterogeneous and may consist of several clones that may limit the effectiveness of subsequent targeted therapies that target only one of the clones.”


  1. Fribbens C, Murillas IG, Beaney M, et al. Tracking evolution of aromatase inhibitor resistance with circulating tumour DNA analysis in metastatic breast cancer. Ann Oncol. 2017 Oct 4. doi: 10.1093/annonc/mdx483 [Epub ahead of print]