Dr Mayer on ESR1 Testing Methods in the SERENA-6 Study of Patients With ER+/HER2– Advanced Breast Cancer

“Patients prefer [mutation testing with ctDNA] as it is noninvasive…and we [saw] in the SERENA-6 study that it is feasible to do…in a serial manner.”

Erica L. Mayer, MD, MPH, director, breast cancer clinical research, Dana-Farber Cancer Institute, and associate professor of medicine, Harvard Medical School, discussed ESR1 mutation detection by circulating tumor DNA (ctDNA) liquid biopsy in the phase 3 SERENA-6 study (NCT04964934).

SERENA-6 examined camizestrant in combination with a CDK4/6 inhibitor vs continuing with aromatase inhibition (AI) plus a CDK4/6 inhibitor in patients with estrogen receptor (ER)–positive, HER2-negative advanced breast cancer who received an AI plus a CDK4/6 inhibitor as their initial endocrine-based therapy for advanced breast cancer for at least 6 months. The study authors hypothesized that using camizestrant to treat emerging ESR1 mutations prior to disease progression could extend the benefit of frontline therapy.

Data from SERENA-6 presented during the 2025 ASCO Annual Meeting showed that patients who received camizestrant (n = 157) achieved a median progression-free survival (PFS) of 16.0 months (95% CI, 12.7-18.2) compared with 9.2 months (95% CI, 7.2-9.5) in the control arm (n = 158; adjusted HR, 0.44; 95% CI, 0.31-0.60; P < .00001). The 24-month PFS rates were 29.7% and 5.4%, respectively. The study authors noted that SERENA-6 was the first global registrational study to demonstrate the clinical utility of ctDNA monitoring to detect and treat emerging resistance in breast cancer.

ctDNA testing in SERENA-6 was performed using the Guardant360 CDx assay, Mayer began. ctDNA testing is often used in clinical practice to identify resistance mutations such as those in ESR1 and this practice is a part of the American Society of Clinical Oncology guidelines, she noted. Any patient with ER-positive breast cancer with evidence of disease progression should undergo ctDNA testing to look for actionable mutations, she added.

Mayer noted that tissue and ctDNA mutation testing can produce discordant results, partially due to tissue testing only examining a certain area and ctDNA encompassing all aspects of tumor heterogeneity. Patients often prefer ctDNA testing as it is noninvasive, she added. In SERENA-6, study authors demonstrated that ESR1 mutation testing by ctDNA can be feasibly performed in a serial manner, she concluded.

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