New breast cancer drug camizestrant shows better outcomes with early ESR1 detection | ASCO 2025

The SERENA-06 clinical trial studied the use of a biomarker test to look for signs of a cancer genetic change before typical tests would show that the cancer was growing in people with hormone-receptor positive, HER2-negative advanced breast cancer.

Researchers used circulating tumor DNA, or ctDNA, testing to find participants whose cancer had the ESR1 genetic mutation, which affects how estrogen-sensitive cancers grow. If they found an ESR1 mutation, people in the study were randomly assigned to stay on standard treatment or switch to the new drug, camizestrant.

Switching to camizestrant kept the cancer from progressing longer than the typical treatment. The study, presented at the annual meeting of the American Society of Clinical Oncology (ASCO) on June 1 and published concurrently in the New England Journal of Medicine, offers promising results for people with advanced breast cancer.

Background

Hormone-receptor positive, HER2-negative breast cancer is the most common type of breast cancer, accounting for 70% of cases. Hormonal therapy is the primary treatment.

Hormonal therapy drugs work in one of three ways to target the estrogen that makes these cancers grow. Selective estrogen receptor degraders (SERDs) break down and reduce the number of estrogen receptors on cancer cells. Selective estrogen receptor modulators (SERMs) block receptors from attaching to estrogen. Aromatase inhibitors (AIs) reduce the amount of estrogen in the body.

People with advanced HR+, HER2- breast cancer get estrogen therapy along with a second drug, known as a targeted CDK 4/6 therapy. The combination is often effective but can stop working as cancer cells change over time. Research seeks to understand why this happens and what can be done to improve quality of life and extend time without cancer growth and survival.

Some answers may be found in the ESR1 gene, which produces a protein involved in how estrogen drives cancer growth. Studies have found that a change or mutation in ESR1 may be a part of why treatment stops working in 40% of people with advanced HR+, HER2- breast cancer who are taking aromatase inhibitors. New blood tests—including the ctDNA test used in this study—can find ESR1 mutations as they emerge, before treatment stops working. CtDNA tests look at the genes of the cancer cell, which are different than the genes in someone’s healthy cells.

Camizestrant is a new SERD that can be given with CDK 4/6 inhibitors in place of aromatase inhibitors, when an ESR1 gene change is found. Prior research supports its effectiveness against HR+, HER2- advanced breast cancer.

Study results

Switching from an aromatase inhibitor to camizestrant after a positive test for ESR1 mutation extended time without cancer growth. The trial tested using ESR1 to guide treatment in 3,256 participants. It also compared the new drug camizestrant to aromatase inhibitor. Participants in the study had ctDNA testing every two to three months. Testing found 315 people with early signs of ESR1 mutation to get either camizestrant or aromatase inhibitor, along with a CDK 4/6 drug.

As of this interim analysis, people with ESR1 mutations who switched from an aromatase inhibitor to camizestrant had an average of 16 months without cancer progression compared to 9.2 months for the group who stayed on an AI. Camizestrant also led to better quality of life. Participants reported almost two years before their symptoms or pain worsened, compared with 6.4 months when taking an AI.

Side effects were similar in the two groups. Camizestrant was more likely to cause neutropenia, which is a low number of white blood cells that increases risk of infection. It also had the added mild side effect of photopsia, or seeing brief flashes of light. Very few people stopped taking camizestrant because of side effects.

What’s next

This is the first study to demonstrate the use of ctDNA monitoring to detect resistance to treatment and guide treatment choices. Based on these results, the FDA awarded breakthrough approval to camizestrant, which may mean this strategy gets to patients faster.

Some unanswered questions remain about how to use this approach with people who are living with breast cancer now. The results, presented by Dr. Nicholas Turner of The Royal Marsden Hospital in the United Kingdom, are part of an interim analysis, looking at just the main targets of the study. The study will later report how these treatments may influence long-term outcomes.

Following the presentation, oncologist Dr. Angela DeMichele of the University of Pennsylvania discussed where to go from here for patients and providers.

According to DeMichele, the final data on how participants do after their cancer progresses following camizestrant will help understand the overall benefit of the strategy to test for ESR1 and switch drugs. Dr. DeMichele also pointed out that frequent testing may be a challenge for both patients and health systems.

While these results will pave the way for future research, both speakers cautioned that ctDNA testing cannot be used right now with other drug decisions without further study.