What Liquid Biopsy and ESR1 Mutations Mean in Breast Cancer

What Liquid Biopsy and ESR1 Mutations Mean in Breast Cancer

A simple blood test can help oncologists track how breast cancer changes over time and find mutations that may open the door to other treatments, according to Dr. Federica Gatti.

Gatti is a medical oncologist at the Regina Elena National Cancer Institute in Rome, Italy. She spoke with CURE at the 2026 European Society for Medical Oncology (ESMO) Congress in Madrid, where she presented a real-world analysis of ESR1 alterations detected through circulating tumor DNA in people with HR-positive, HER2-negative metastatic breast cancer.

What Is a Liquid Biopsy?

A liquid biopsy is a blood test that patients can have done repeatedly, Gatti explained. It helps oncologists see how the cancer is changing and which mutations the cancer cells have developed. That information can guide which treatment may work best.

What Does an ESR1 Mutation Mean for Patients?

An ESR1 mutation means the tumor has become resistant to endocrine (hormone) therapy, but Gatti stressed that patients still have options. Available treatments vary by country. In Italy, patients with an ESR1 mutation can receive Orserdu (elacestrant), a drug that degrades the estrogen receptor. Gatti said she hopes other drugs showing important results, such as Etcamah (camizestrant), studied in the SERENA-6 trial, will become available to patients in Italy.

“The patient must know that their tumor has endocrine resistance, but there are many options available,” she said.

What Should Patients Ask About Genomic Testing?

Gatti encouraged patients to ask their oncologist which mutations their test found. Besides ESR1, these may include PIK3CA, AKT and PTEN mutations, or rarer ones, any of which could make other drugs an option.

Testing can be repeated when the disease progresses and there is a reason to consider a targeted therapy. Some patients continue to respond to endocrine therapy, while others may need treatments such as chemotherapy or antibody-drug conjugates.

“It’s an important evaluation that the oncologist should share with the patient,” Gatti said.

Transcript

What is a liquid biopsy, and why might a patient with HR-positive metastatic breast cancer have one?

Gatti: A liquid biopsy is a blood test. It’s a very simple test that patients can do every time, and it helps us as oncologists know how the cancer changes. We want to analyze which mutations the cancer cells may develop, and this is very helpful for us to understand which treatment could be best for our patients.

If a patient learns their cancer has an ESR1 mutation, what does that mean for them, and what treatment options are available?

In different countries, there are different options available. For example, in Italy, an ESR1 mutation allows the patient to receive elacestrant, a degrader of the estrogen receptor, which helps us overcome endocrine resistance. We hope that for our patients in Italy, we could prescribe other drugs that are showing important results, like camizestrant with the SERENA-6 trial, for example. So the patient must know that their tumor has endocrine resistance, but there are many options available.

What questions should patients ask their oncologist about genomic test results, and how often might those tests be repeated?

Patients should ask their oncologist which mutations were observed in their test: whether there is an ESR1 mutation, but also other mutations, for example PIK3CA, AKT or PTEN, that can allow the patient to receive other drugs, or even other mutations that are less frequent. The test could be repeated every time the patient’s disease progresses, when there is a rationale for a targeted therapy. We know that some patients respond to endocrine therapy, but other patients who progress need other treatments, like chemotherapy or ADCs, for example. So it’s an important evaluation that the oncologist should share with the patient.

This transcript has been edited for clarity and conciseness.

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