Study: Treating advanced breast cancer with ESR1 mutations shows promise

RELEVANCE

Most relevant for: People with ER-positive, HER2-negative advanced breast cancer with ESR1 mutations.

It may also be relevant for:

• people with breast cancer
• people with ER/PR + cancer
• people with metastatic or advanced cancer

Relevance: Medium-High

Strength of Science: High

Research Timeline: Human Research

More rating details

What is this study about?

This study evaluated whether a new hormonal therapy called camizestrant could improve treatment for advanced HR-positive, HER2-negative breast cancer patients whose tumors had a change known as an ESR1 mutation.

Researchers also studied whether blood tests used to track ESR1 gene mutations could help doctors spot treatment resistance earlier by detecting ESR1 tumor mutations before symptoms or scans showed a problem. This approach, which uses a type of liquid biopsy, can help doctors decide earlier whether a change in treatments is necessary.  You can read more about liquid biopsies for monitoring treatment response here.

Why is this study important?

Many people with advanced or metastatic cancer receive treatment that initially works well. However, cancer treatments may stop working when tumor mutations that promote cancer growth occur. This is referred to as treatment resistance.  A common type of treatment resistance in HR-positive breast cancers happens when mutations in the estrogen receptor 1 (ESR1) gene occur. About 5% of people have ESR1 tumor mutations when their cancer treatment begins. About 40% of people with metastatic breast cancer acquire ESR1 mutations in their tumors and develop resistance to hormonal therapies during their treatment.

Researchers have been looking for a way to reverse ESR1-related tumor resistance. Camizestrant may be one way to do that. This drug is a SERD (Selective Estrogen Receptor Degrader), a type of hormonal therapy designed to help block the growth of tumors with ESR1 mutations. Camizestrant is not yet approved by the FDA for general use; it is currently available only through clinical trials.

A similar drug, Oserdu (elacestrant), received FDA approval in 2023 for the treatment of metastatic or advanced HR-positive, HER2-negative breast cancer. You can read our XRAY review here.

Study design

This phase 3 study enrolled 3,256 people with advanced HR-positive, HER2-negative breast cancer that returned or spread to other parts of the body. Participants previously received at least six months of standard treatment, including a hormone-reducing treatment (an aromatase inhibitor) and a type of targeted therapy known as a CDK4/6 inhibitor (a drug that stops cell growth).

Participants had liquid biopsy blood tests every 2 to 3 months to monitor for ESR1 mutations. Of the 3,256 participants, 315 developed ESR1 mutations based on their blood test, which were identified before symptoms or imaging scans indicated that their cancer was no longer responding to treatment.

 The participants with ESR1 tumor mutations were randomly assigned to one of two groups. All participants also received a checkpoint inhibitor.

• Camizestrant group (157 patients): These participants were switched from the hormone-blocking treatment to camizestrant.
• Standard therapy group (158 patients): These participants continued receiving the same hormone-reducing (aromatase inhibitor) therapy.

Neither the patients nor their doctors knew which treatment they were receiving (a double-blind study). Study participants completed surveys throughout the study regarding their health status and quality-of-life.

Study findings

Participants in the camizestrant group responded to treatment better than the standard treatment group in the following ways:

•  Longer time without cancer growth:
  • Patients who received camizestrant went 17 months before their cancer showed signs of growth.
  • Patients who continued receiving standard hormone therapy went 9 months before their cancer showed signs of growth.
• Fewer ESR1 mutations:
  • Patients in the camizestrant group had fewer ESR1 mutations in their cancer cells compared to the standard treatment group, indicating that camizestrant may be reducing resistance to treatment.
• At 2 years, more people survived and had no cancer growth:
  • 30% of patients who received camizestrant were alive with no signs that their cancer was growing.
  • 5% of patients who continued receiving standard therapy (instead of switching to camizestrant) were alive with no signs that their cancer was growing.
  • It is too early to know if treatment with camizestrant leads to longer overall survival. So far, the number of deaths from any cause in the two study groups is similar.
• Longer time before cancer grew on later lines of treatment:
  • If a participant’s cancer grew, regardless of the study group they were in, they were switched to a different second line of treatment selected by their doctor.
  • The participants who had been in the camizestrant group went longer (26 months) before their cancer grew on this next line of treatment, compared to the participants who had been in the AI group (19 months).
• High quality of life lasted longer:
  • Participants in the camizestrant group reported feeling well for much longer (21 months) before experiencing worsening health or quality of life.
  • Those in the standard treatment group reported worsening health status or quality of life sooner (6 months).

The longer quality of life in the camizestrant group was related to less pain, fatigue and shortness of breath, fewer breast or arm symptoms, and better overall physical and emotional functions.

Side effects

Most participants in both groups experienced some side effects during treatment (93% of camizestrant group and 87% of the standard of care group). However, most participants in both groups reported that they were either “not at all” or “a little bit” bothered by side effects (86% in the camizestrant group and 82% in the AI group).

The most common mild or moderate side effects were:

• Visual disturbances in which patients saw short flashes of light in their peripheral vision (more common in the camizestrant group).
  •  This side effect was mild and had no or minimal effect on daily activities. Eye exams did not show eye damage or important changes in vision.
• Abnormally slow heart rate (bradycardia)
  • This occurred in 8% of camizestrant group and none of the AI group. All cases were mild or moderate severity.
• Low red blood cell count (anemia)
• Dry eyes
• Joint pain
• Fatigue

More serious side effects occurred in the camizestrant group (60%) than in the standard therapy group (46%).

• The most common serious side effect in both groups was a low level of white blood cells called neutrophils (neutropenia). This finding was not surprising since neutropenia is a known side effect of the checkpoint inhibitors that all study participants received.
  • 55% of participants in the camizestrant group experienced neutropenia compared to 44% in the standard therapy group.
  • Severe or life-threatening neutropenia occurred in 45% of the camizestrant group and 34% of the standard therapy group.  
• 4 participants who had serious side effects died within a month of stopping treatment (3 in the camizestrant group and one in the standard therapy group). However, only one death in each group was thought to be related to cancer treatment.    

What does this mean for me?

This study suggests that camizestrant treatment may delay cancer growth for people with advanced ER-positive, HER2-negative breast cancer that has ESR1 gene mutations. More specifically, the findings suggest that:

• Camizestrant may be a helpful option when cancer begins to change and before scans can detect problems.
• Using liquid biopsy blood tests to track whether ESR1 mutations occur in cancer may be beneficial for understanding how the cancer is responding to treatment.

If you have advanced breast cancer and are taking an aromatase inhibitor and a CDK4/6 inhibitor, the results of this study may provide information on how your doctors can best manage your treatment in the future. However, camizestrant is not yet approved for use by the FDA outside of a clinical trial.

Reference

Bidard F, Mayer E, Park Y, et al. First-Line camizestrant for emerging ESR1-mutated Advanced Breast Cancer. N Engl J Med. 2025;393(6):569-580.

Mayer EL, Bidard F-C, Park Y, et al. Patient-reported outcomes in the SERENA-6 trial of camizestrant plus CDK4/6 inhibitor in patients with advanced breast cancer and emergent ESR1 mutations during first-line endocrine-based therapy. 2026. Annals of Oncology, Volume 37, Issue 2, 180 – 193.

Bidard F, Mayer E, Park Y, et al. Updated results and exploratory analysis of ESR1m circulating tumor DNA dynamics from SERENA-6, a phase 3 trial of camizesstrant +/- CDK4/6 inhibitor for emergent ESR1m during first line endocrine-based therapy and ahead of disease progression in patients with ER+/HER2- advanced breast cancer. 2025. San Antonio Breast Cancer Symposium. Presented Dec 12, 2026.

Disclosure: FORCE receives funding from industry sponsors, including companies that manufacture cancer drugs, tests and devices. All XRAYS articles are written independently of any sponsor and are reviewed by members of our Scientific Advisory Board prior to publication to assure scientific integrity.

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posted 2/19/26