The American Society of Clinical Oncology (ASCO) has released an updated guideline recommending testing for ESR1 mutations in certain patients with advanced breast cancer. The update was published in the Journal of Clinical Oncology.1

Routine testing for ESR1 mutations should occur upon recurrence or progression of hormone receptor (HR)-positive, HER2-negative metastatic breast cancer, the guideline authors recommend.

The updated guideline reflects the findings of EMERALD, a phase 3 trial in which advanced breast cancer patients with detectable ESR1 mutations in circulating tumor DNA (ctDNA) had significantly improved progression-free survival with elacestrant compared with standard-of-care endocrine therapy (ET).2 Patients without ESR1 mutations did not experience an improvement with elacestrant.

The guideline therefore recommends routine testing for ESR1 mutations when patients with HR-positive, HER2-negative metastatic breast cancer experience recurrence or progression on ET (with or without a CDK4/6 inhibitor).

“Testing with a Clinical Laboratory Improvement Amendments–certified assay should be performed on blood or tissue obtained at the time of progression, as ESR1 mutations develop in response to selection pressure during treatment and are typically undetectable in the primary tumor,” the authors wrote. “Blood-based ctDNA is preferred owing to greater sensitivity.”

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Patients whose test results do not reveal ESR1 mutations may be tested again at subsequent disease progression. The guideline also recommends testing for PIK3CA mutations to guide therapy as well.

There are several treatment options for patients with advanced breast cancer previously treated with ET and a CDK4/6 inhibitor.

For patients with ESR1 mutations, treatment options include elacestrant or another type of ET either alone or in combination with targeted agents such as everolimus or alpelisib for PIK3CA-mutated tumors.

For patients with ESR1 wild-type tumors, ET options include fulvestrant, an aromatase inhibitor, or tamoxifen monotherapy, or ET in combination with targeted agents such as everolimus or alpelisib for PIK3CA-mutated tumors.

Disclosures: Some authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


1. Burstein HJ, DeMichele A, Somerfield MR, Henry NL. Testing for ESR1 mutations to guide therapy for hormone receptor–positive, human epidermal growth factor receptor 2–negative metastatic breast cancer: ASCO guideline rapid recommendation update. J Clin Oncol. Published online May 17, 2023. doi:10.1200/JCO.23.00638

2. Nye J. Duration of prior CDK4/6 inhibitor treatment tied to PFS with elacestrant. Cancer Therapy Advisor. Published December 8, 2022. Accessed May 18, 2023.

This article originally appeared on Cancer Therapy Advisor