Many people with advanced hormone-sensitive (ER-positive) breast cancer develop a specific genetic change in their cancer called an ESR1 mutation over time. This mutation can make standard hormone therapies (like aromatase inhibitors) less effective. Camizestrant is a new type of hormone therapy designed to work even when ESR1 mutations develop. Recent results from the SERENA-6 Phase III clinical trial were presented at the 2025 American Society of Clinical Oncology Annual Meeting and simultaneously published in the New England Journal of Medicine.
SERENA-6 Phase III Clinical Trial
- Researchers monitored 3,256 patients with advanced ER-positive, HER2-negative breast cancer using ctDNA monitoring to detect resistance before disease progression
- All participants had already been on standard treatment (aromatase inhibitor + a CDK4/6 inhibitor drug) for at least 6 months.
- An ESR1 mutation was detected before the cancer visibly worsened in 315 patients. These patients were split into two groups:
- Switched to camizestrant (kept taking their CDK4/6 inhibitor).
- Continued standard hormone therapy (kept taking their CDK4/6 inhibitor).
Key Findings
- Patients who switched to camizestrant lived an average of 16 months without their cancer getting worse, compared to 9.2 months for those who stayed on standard hormone therapy.
- The risk of cancer progression or death was reduced by 56% with camizestrant.
- The benefit was seen no matter which CDK4/6 inhibitor was used, and across different patient groups.
- Quality of Life:
- Patients on camizestrant also maintained their quality of life for much longer — about 23 months compared to 6.4 months with standard therapy.
- Camizestrant also helped delay the worsening of pain.
- Safety:
- The side effects of camizestrant were similar to what is already known for these types of medicines. Most side effects were related to the CDK4/6 inhibitors (like low white blood cells).
- Very few people had to stop treatment due to side effects.
Updated results presented at the 2025 San Antonio Breast Cancer Symposium showed that switching to camizestrant significantly extended the time before the cancer worsened. Median progression‑free survival was 16.6 months with camizestrant plus CDK4/6 inhibition, compared with 9.2 months for those who continued on an aromatase inhibitor with CDK4/6 therapy—an improvement of more than 7 months and roughly a 54% reduction in the risk of progression. The camizestrant strategy also lengthened the time until patients needed their next treatment, delayed the start of chemotherapy or antibody–drug conjugates, and improved second progression‑free survival (PFS2), suggesting that the benefits carried forward into subsequent lines of therapy.
Why Is This Important?
This is the first big study to show that monitoring for ESR1 mutations and switching treatment early can make a real difference for patients. It means doctors can act before the cancer gets worse, giving you more time with effective treatment and a better quality of life.
What Happens Next?
- Camizestrant is not yet available outside of a clinical trial but has received special recognition in the US (Breakthrough Therapy Designation) because of these promising results.
- The study will continue to follow patients to see if there are long-term survival benefits.
If you have advanced HR-positive, HER2-negative breast cancer and are on a CDK4/6 inhibitor with hormone therapy, ask your doctor about ESR1 mutation testing and whether new treatment options like camizestrant might be right for you in the future.
More Reading
Treatment & Management of Breast Cancer
Learn How ctDNA Testing Can Help Inform Breast Cancer Management
Join the conversation on Cancer Connect.
Reference
Bidard F-C, Mayer EL, Hee Park Y, et al. First-Line Camizestrant for Emerging ESR1-Mutated Advanced Breast Cancer. NEJM. Published online: June 1, 2025.
Turner N, Mayer E, Park YH, 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. J Clin Oncol. 2025;43(suppl 17):LBA4.
Bidard FC, Mayer EL, Park YH, et al. Updated results and an exploratory analysis of ESR1m circulating tumor DNA dynamics from SERENA-6, a phase 3 trial of camizestrant + CDK4/6 inhibitor for emergent ESR1m during first-line endocrine-based therapy and ahead of disease progression in patients with HR+/HER2– advanced breast cancer. Presented at: 2025 San Antonio Breast Cancer Symposium; December 9-12, 2025; San Antonio, TX. Abstract RF7-03.
