Understanding ESR1 Mutations in Advanced Breast Cancer

If you are a man or woman living with advanced or metastatic breast cancer, you may hear your doctor talk about "biomarkers." Biomarkers are specific traits that help doctors understand how your cancer grows. One important biomarker is called an ESR1 mutation.¹

It is important to know that finding this change is not your fault. It does not mean your previous treatment failed because of something you did. Instead, it means the cancer has found a new way to grow.

What is an ESR1 mutation?

Most breast cancers are estrogen receptor-positive (ER+). This means the cancer cells use the hormone estrogen as fuel to grow. Many treatments work by blocking estrogen or the receptors that catch it. Think of the estrogen receptor as a lock on the cancer cell. Estrogen is the key that fits into the lock to turn the cell "on" so it grows.¹

Standard hormone therapies, like aromatase inhibitors, work by taking away the "keys." Without estrogen, the lock stays closed. However, breast cancer is smart. Over time, it can "learn" how to grow without the key. The cancer cell changes the shape of the lock so it stays stuck in the "open" position. This change is the ESR1 mutation. Now, the cell grows even when no estrogen is around.¹

Finding the mutation with a liquid biopsy

In the past, doctors needed a piece of tumor tissue to look for mutations. This is called a tissue biopsy. Today, doctors can often find ESR1 mutations using a liquid biopsy. This is a simple blood test.¹

As cancer cells grow and die, they release tiny bits of their DNA into your bloodstream. A liquid biopsy looks for this "cell-free DNA." This test allows your medical team to see if your cancer has changed without needing a surgical procedure. If you have had at least one type of hormone therapy and your cancer has progressed, your doctor may order this test to see if an ESR1 mutation is present.¹

Moving to the next generation of treatment

When an ESR1 mutation is found, it is a signal that it is time to change your "tools." Standard hormone pills may no longer work because the "lock" is broken. This is where oral SERDs (Selective Estrogen Receptor Degraders) come into play.^1-3

While older treatments try to block the lock, oral SERDs are designed to remove the broken lock entirely. They attach to the mutated estrogen receptor and cause the cell to break it down. By getting rid of the broken locks, the treatment helps stop the cancer from growing. This is a "next-generation" approach specifically made to target these mutated cells.^1-3

The US Food and Drug Administration (FDA) has approved the following oral SERDs for people with ESR1 mutations:^2-5

• Elacestrant (Orserdu®) – the first oral SERD approved in 2023. It is approved for the treatment of postmenopausal women or adult men with ER-positive, HER2‑negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least 1 line of hormone therapy.
• Imlunestrant (Inluriyo®) – approved in 2025. It is approved for the treatment of adults with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least 1 line of hormone therapy.

What this means for you

Learning that your cancer has changed can feel scary. However, identifying an ESR1 mutation is a helpful step. It gives your doctor a clear target. It helps them choose the most effective next step for your specific type of cancer.

If you have ER-positive, HER2-negative advanced breast cancer, talk to your doctor about biomarker testing. Ask if a liquid biopsy for ESR1 mutations is right for you. Understanding the biology of your cancer helps you and your care team stay one step ahead.^1-3