ctDNA-Guided Therapy May Improve Breast Cancer Outcomes

For patients with metastatic hormone receptor (HR)-positive, HER2-negative breast cancer, there were various trials to have come out of the 2025 ASCO Annual Meeting that are worth keeping your eye on, Dr. Julia E. McGuinness said in an interview with Dr. Joshua K. Sabari. Notably, of those trials was the SERENA-6 trial.

What the SERENA-6 trial aimed to answer was if detecting ESR1 mutations prior to disease progression could help extend the effectiveness of first-line treatment for those with breast cancer. ctDNA are small pieces of DNA which can be detected and are released by tumor cells into a person’s blood, and if detected early, has the potential to guide treatment decisions. With this in mind, McGuinness explained that using ctDNA to guide treatment decisions for those within this patient population improved patient outcomes.

"[Investigators] tried to identify women who developed an ESR1 mutation during their first-line treatment. What they did was what we call serial testing, or serial liquid biopsies. They did blood tests every three months to look for changes in the circulating tumor cells in the blood to see if they could detect an ESR1 mutation," she explained.

If a mutation was detected, some patients were switched early to camizestrant treatment in combination with CDK4/6 inhibition. However, those who got the standard of care regimen remained on their original treatment until disease progression.

Investigators found that those who had detected disease and were treated with the investigative combination responded better those who continued standard of care therapy prior to disease progression on therapy.

McGuinness concluded by stating that, “Ultimately, what we're trying to do with any of these treatments is make women live longer, and that's called overall survival; that is going to take a while to read out. We may have to wait for some of these longer-term outcomes before we actually make such a big switch [in care].”

McGuinness is a medical oncologist and serves as an assistant professor of medicine within the Division of Hematology/Oncology at Columbia University Irving Medical Center, Columbia University Herbert Irving Comprehensive Cancer Center, located in New York. Sabari is the editor in chief of CURE. He also serves as an assistant professor in the Department of Medicine at NYU Grossman School of Medicine and director of High Reliability Organization Initiatives at Perlmutter Cancer Center.

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