Testing for ESR1 Mutations in Breast Cancer

This is a synopsis of an Insights series featuring Kevin Kalinsky, MD, MS, of Winship Cancer Institute of Emory University, and Erica L. Mayer, MD, MPH, of Dana-Farber Cancer Institute.

Dr Kevin Kalinsky, director of the Glenn Family Breast Center at Winship Cancer Institute, and Dr Erica Mayer, director of Breast Cancer Clinical Research at Dana-Farber Cancer Institute, discussed evolving treatment approaches for hormone receptor-positive (HR+) metastatic breast cancer, focusing on the impact of estrogen receptor (ER) mutations.

Dr Mayer outlined current standards for genomic profiling in metastatic HR+ breast cancer, including tumor tissue-based testing and cell-free DNA (cfDNA) analysis from liquid biopsies. Liquid biopsies can provide a comprehensive snapshot of cancer genetics and allow for serial monitoring of mutations over time, especially at progression. She obtains baseline tissue testing but prefers serial cfDNA analysis to track genomic evolution.

The speakers focused particularly on ESR1 mutations, which confer endocrine therapy resistance. Unlike trunk mutations present at diagnosis, ESR1 mutations often emerge later, so tissue testing may underestimate prevalence. Dr. Mayer does not routinely order cfDNA testing for endocrine-sensitive disease but finds it valuable in certain contexts: patients on extended adjuvant aromatase inhibitor therapy approaching metastasis, and patients progressing rapidly on aromatase inhibitors, indicating probable resistance. In the latter case, ESR1 mutations would prompt use of non-aromatase inhibitor therapies like fulvestrant rather than continuing aromatase inhibitors plus CDK4/6 inhibitors.

Dr Kalinsky agreed, noting ESR1 mutation testing is most relevant in deciding between endocrine therapies versus more targeted options when resistance emerges. He often orders testing around the time of clinical progression, scheduling a few weeks in advance to inform next-line decisions at the patient visit. Having real-time mutation data enables personalized therapy selection.

Overall, Drs Mayer and Kalinsky emphasized that advancing genomic profiling capabilities allow deeper understanding of the heterogeneity and evolution of HR+ metastatic breast cancer. Serial liquid biopsy testing for mutations like ESR1 that mediate endocrine resistance at progression enables more informed, personalized therapy selection to overcome tumor adaptation. Their discussion highlights how genomic information is transforming real-time clinical decision-making in this disease.

*Video synopsis is AI-generated and reviewed by OncLive editorial staff.