PEOPLE WITH METASTATIC BREAST CANCER often switch to new treatments once scans show cancer growth. However, a recent study showed that changing treatment earlier—when a blood test catches early signs of resistance—may help people with metastatic hormone receptor-positive breast cancer control their disease for longer.

Hormone receptor-positive, HER2-negative is the most prevalent subtype of breast cancer, representing about 70% of cases. People with this diagnosis typically receive an aromatase inhibitor, which lowers the amount of estrogen in the body, paired with a type of targeted therapy called a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor.

However, after exposure to aromatase inhibitors, cancer cells can develop ESR1 mutations, which may signal that the disease is not responding to the treatment. Patients whose cancer progresses will often receive a selective estrogen receptor degrader (SERD), such as fulvestrant. SERDs are medications that bind to estrogen receptors in cancer cells and cause them to break down.

Findings from the SERENA-6 clinical trial, published June 1, 2025, in the New England Journal of Medicine, found that patients who switched from an aromatase inhibitor to a SERD once blood tests detected ESR1 mutations had longer cancer control and better quality of life compared with those who continued treatment with an aromatase inhibitor.

The phase III clinical trial included 315 people with metastatic hormone receptor-positive, HER2-negative breast cancer whose blood samples tested positive for ESR1 mutations. Half of the patients continued taking an aromatase inhibitor and a CDK4/6 inhibitor, while the others changed to an investigational SERD called camizestrant while continuing to take a CDK4/6 inhibitor. Camizestrant, which is taken orally, is not approved by the Food and Drug Administration.

People who switched to camizestrant went a median of 16 months without cancer progression, compared with 9.2 months for those who continued their previous treatment. In addition, people who switched to camizestrant went 21 months before they experienced a deterioration in quality of life, according to their responses on a questionnaire. Those who continued taking an aromatase inhibitor reported a deterioration in quality of life at 6.4 months.

However, earlier research published in 2022 showed that people with metastatic hormone receptor-positive breast cancer whose blood samples tested positive for an ESR1 mutation lived 11.9 months without cancer progression if they switched from an aromatase inhibitor to fulvestrant. Those who continued taking aromatase inhibitors despite detection of ESR1 mutations went 5.7 months without progression. Both groups also received a CDK4/6 inhibitor. While camizestrant is being studied in clinical trials, fulvestrant, which is injected into the muscle, is approved for use in metastatic breast cancer that has progressed after anti-estrogen therapies, like aromatase inhibitors.

The combination of an aromatase inhibitor and a CDK4/6 inhibitor typically delays progression for two to three years in first-line treatment, according to Matthew Goetz, a medical oncologist at Mayo Clinic in Rochester, Minnesota, whose research focuses on hormone receptor-positive breast cancer. People with metastatic breast cancer receiving first-line therapy get scans every few months, and when imaging reveals disease progression, they switch treatments. The new approach would just switch them sooner, says Goetz, who enrolled patients for this trial but was not an investigator for this study.

“Switching early—before this clinical progression happens—buys time,” says Lajos Pusztai, a medical oncologist at Smilow Cancer Hospital at Yale New Haven in Connecticut, who was not involved in the study.

The blood tests used in the studies examined circulating tumor DNA (ctDNA), fragments of DNA shed by tumor cells that have entered the bloodstream, for specific genetic changes. In the latest study, patients received blood tests to detect ESR1 mutations every two to three months.

“The most immediate need is longer follow-up from SERENA-6 to determine whether the early-switch strategy improves overall survival,” says Yara Abdou, a medical oncologist who leads the breast cancer clinical trial program at UNC Lineberger Comprehensive Cancer Center in Chapel Hill, North Carolina, and who was not involved in the study. “Beyond that, we need studies that clarify how often ctDNA testing should be done in practice—every two months, every three months or less frequently—and whether we can refine testing to detect not only ESR1 but other mutations that may drive resistance.”

Goetz is also interested in the long-term outcomes from this trial. “What clinicians want to know is what is the sequence of therapy that will lead to the best long-term outcome survival—while maintaining quality of life,” Goetz says.