Treatment Switching Guided by Liquid Biopsy Blood Tests Improves Outcomes for Breast Cancer Patients

Standard treatment for patients with advanced estrogen receptor (ER)-positive, HER2-negative breast cancer, a subtype driven by estrogen receptors that fuel tumor growth, often involves aromatase inhibitors, which suppress estrogen production. However, resistance frequently develops when tumors acquire ESR1 gene mutations, keeping estrogen receptors active even without hormones. A major clinical challenge in treating advanced ER-positive breast cancer is detecting resistance mutations early enough to adjust treatment before tumor progression occurs. A new international trial has now shown that using liquid biopsy blood tests to identify these mutations, specifically in the ESR1 gene, followed by a timely switch to a novel drug, can significantly extend the period of tumor control compared to standard treatment.

The findings come from the SERENA-6 study, a large-scale, randomized clinical trial conducted across 264 clinical sites in 23 countries, including major contributions from Weill Cornell Medicine (New York, NY, USA). The study, overseen by a team of international researchers and clinicians, focused on patients with advanced ER-positive, HER2-negative breast cancer. The researchers explored whether switching patients to an experimental drug—camizestrant—at the first detection of ESR1 mutations via liquid biopsy, rather than waiting for imaging or symptoms, would improve outcomes. Camizestrant works by directly reducing the number of estrogen receptors on cancer cells, targeting the root of the resistance. Of more than 3,300 patients screened, 315 with detectable ESR1 mutations but no visible disease progression were randomly assigned to either switch to camizestrant or continue aromatase inhibitor therapy.

Image: Switching to an experimental drug after liquid biopsy detection of breast cancer recurrence can improve outcomes (Photo courtesy of Shutterstock)

The findings published in the New England Journal of Medicine clearly show that patients who transitioned early to camizestrant experienced a median tumor progression-free period of 16.0 months, compared to 9.2 months with standard care. Even more strikingly, overall health deterioration was delayed to a median of 23.0 months in the camizestrant group, versus just 6.4 months in the control group. These results were considered both statistically and clinically significant. Camizestrant was also well tolerated, with a few patients discontinuing it due to side effects. The findings mark one of the first successful demonstrations that treatment adaptation based on liquid biopsy results can improve patient outcomes in real-world clinical settings. This trial not only validates liquid biopsy as a viable early monitoring tool in breast cancer but also paves the way for similar approaches in other cancers where resistance mutations can be detected in blood. For ER-positive breast cancer, in particular, the strategy could redefine how clinicians monitor recurrence and make proactive treatment decisions.

“The main message here is that liquid biopsy technology allows us to intervene sooner when the tumor burden is lower and the chance of a good outcome is higher,” said study co-author Dr. Massimo Cristofanilli, who helped design and oversee the SERENA-6 study.