Testing for ESR1 Mutations, Then Switching to Camizestrant Improves Outcomes for Metastatic HR+ HER2- Breast Cancer
Published on June 1, 2025
Finding ESR1 mutations in metastatic hormone receptor-positive, HER2-negative breast cancer before the cancer grows and then switching the first hormonal therapy treatment — from an aromatase inhibitor and a CDK4/6 inhibitor to camizestrant and a CDK4/6 inhibitor — led to better progression-free survival. Progression-free survival is how long people live without the cancer growing.
The results of the SERENA-6 trial were presented at the 2025 American Society of Clinical Oncology Annual Meeting (ASCO) and published simultaneously in The New England Journal of Medicine.
Key takeaways
Switching from an aromatase inhibitor to camizestrant, a type of hormonal therapy called a SERD, reduced the risk of the cancer growing or of people dying from breast cancer by 56%.
Progression-free survival was 16 months for people who switched to camizestrant versus 9 months for people who stayed on an aromatase inhibitor.
The people in the study were tested for ESR1 mutations every two to three months during treatment; this type of testing — a blood test called a liquid biopsy to look for circulating tumor DNA (ctDNA) — usually isn’t done until the cancer grows.
What this means for you
Although the results of this study are promising, it’s important to know that camizestrant is not yet approved by the U.S. Food and Drug Administration (FDA) and the researchers aren’t sure when it will be approved. While other SERDs, like Orserdu (chemical name: elacestrant) are FDA-approved for metastatic breast cancers with an ESR1 mutation, researchers don’t know if using Orserdu in the same way would offer similar benefits.
Checking for ESR1 mutations every few months is also not routinely done, and insurance companies may not pay for routine ctDNA tests. The costs of the tests range from about $500 to several thousand dollars.
If you’ve been diagnosed with metastatic hormone-receptor-positive, HER2-negative breast cancer and are starting first hormonal therapy treatments with an aromatase inhibitor and a CDK4/6 inhibitor, you may want to ask your doctor about this study and if it’s possible for you to have routine ctDNA testing.
Why do the study
ESR1 mutations are rare when metastatic hormone receptor-positive, HER2-negative breast cancer is first diagnosed. But after treatment with an aromatase inhibitor, about 40% of these cancers develop the mutation. Because these mutations cause the cancer to become resistant to the aromatase inhibitor, the cancer often grows after they develop.
Other treatment options exist at this point, explained lead study author Nicholas Turner, MD, PhD, FMedSci, of London’s Royal Marsden Hospital. “However, their benefit is limited; quality of life decreases, and survival rates are low. Patients have an urgent need for new treatments that can prolong time on first-line therapy and delay disease progression.”
Previous research has shown that ctDNA testing can often detect ESR1 mutations about six months before cancers grow. The researchers wanted to know if, for cancers with ESR1 mutations, switching to camizestrant treatment before the cancer grew would lengthen progression-free survival.
About the study
The SERENA-6 trial included more than 3,250 people with metastatic hormone receptor-positive, HER2-negative breast cancer. The cancers had been treated for at least six months with an aromatase inhibitor and a CDK4/6 inhibitor; testing for ESR1 mutations was done every two to three months. Overall, 548 cancers developed ESR1 mutations. About 50% of these had an ESR1 mutation detected during the first ctDNA test.
Of the people with cancers with ESR1 mutations, 233 left the study either because the cancer had grown when the ESR1 mutation was found or for other reasons.
The 315 who stayed in the study were randomly assigned to one of two treatments along with a CDK4/6 inhibitor:
158 people continued to take an aromatase inhibitor and also took a placebo pill that looked just like camizestrant but contained no medicine
157 people switched to camizestrant and also took a placebo pill that looked just like an aromatase inhibitor but contained no medicine
Detailed results
After one year of follow-up, the progression-free survival rate was:
61% for people taking camizestrant
33% for people taking an aromatase inhibitor
After two years of follow-up, the progression-free survival rate was:
29.7% for people taking camizestrant
5.4% for people taking an aromatase inhibitor
Switching to camizestrant also led to better quality of life. People who switched went nearly two years before their quality of life went down compared to six months for people who stayed on an aromatase inhibitor.
Fewer than 2% of people in either group stopped treatment because of side effects.
The results from the trial, said Turner, “represent an important step forward and a potential new treatment strategy to improve first-line outcomes for patients.”
Turner, N., et al. Camizestrant + CDK4/6 inhibitor (CDK4/6i) for the treatment of emergent ESR1 mutations during first-line (1L) endocrine-based therapy (ET) and ahead of disease progression in patients (pts) with HR+/HER2– advanced breast cancer (ABC): Phase 3, double-blind ctDNA-guided SERENA-6 trial. 2025 American Society of Clinical Oncology Annual Meeting. Abstract LBA4.
This content is made possible by Lilly.