By Maryam Lustberg, MD, MPH, as told to Keri Wiginton
Lustberg is director of the Center for Breast Cancer at Smilow Cancer Hospital and Yale Cancer Center, chief of breast medical oncology at Yale Cancer Center, and professor of medicine (medical oncology) at Yale School of Medicine. The information here reflects her clinical knowledge and experience. She was not involved in the development of imlunestrant (Inluriyo).
Hormone therapy can control hormone receptor-positive breast cancer for months or years. But cancer cells can change over time and find new ways to grow. One common change in advanced breast cancer is an ESR1 mutation, which affects the estrogen receptor inside the cancer cell.
Imlunestrant (Inluriyo) is an oral selective estrogen receptor degrader, or SERD. It attaches to estrogen receptors and helps break them down, cutting off a key growth signal used by estrogen receptor-positive breast cancer cells.
The FDA approved imlunestrant in September 2025. Here’s what to know about who it’s for, how well the drug works, and what treatment may involve.
Who may benefit from imlunestrant?
Imlunestrant is approved for adults whose breast cancer is:
- Estrogen receptor-positive
- HER2-negative
- Advanced or metastatic
- Positive for an ESR1 mutation
- Growing during or after at least one endocrine therapy
This treatment may be right for you if an earlier hormone-based treatment, such as an aromatase inhibitor, has stopped controlling the cancer. You may also benefit if you’ve already received a CDK4/6 inhibitor, such as abemaciclib, palbociclib, or ribociclib.
Why does ESR1 testing matter?
An ESR1 mutation can keep the estrogen receptor active even when estrogen levels are very low. That means the cancer may continue to get growth signals after an aromatase inhibitor lowers the amount of estrogen in your body.
These mutations often develop after long-term endocrine therapy. If treatment stops working, testing again can uncover changes that weren’t present earlier and help guide next steps in care.
Your doctor can look for ESR1 mutations and other tumor-related changes in a type of blood sample called a liquid biopsy or on newly collected tumor tissue. These tests look for tumor DNA and help show what may be driving your cancer now and which targeted treatments could be a good fit.
ESR1 is one of several gene changes that can guide treatment. Ask if you’ve had genomic testing and what the results mean for your choices.
How does imlunestrant work?
Estrogen receptor-positive breast cancer gets growth signals through estrogen receptors.
Aromatase inhibitors lower the amount of estrogen available to send those signals. Imlunestrant works in a different way. It attaches to the estrogen receptor itself, blocks its activity, and helps the cell break the receptor down.
Think of the receptor as a docking spot for estrogen. By reducing the number of docking spots, imlunestrant can help slow the growth of tumors that have become resistant to earlier hormone treatments.
Where does imlunestrant fit in treatment?
Imlunestrant may be an option after at least one endocrine therapy stops controlling advanced or metastatic breast cancer. That’s often when an ESR1 mutation has developed and a different way of blocking estrogen signals may help.
Clinical trials studied imlunestrant in people whose cancer had progressed after an aromatase inhibitor, either alone or with a CDK4/6 inhibitor.
Your oncologist will look at your full treatment history, how quickly the cancer is changing, where it has spread, other tumor mutations, past side effects, and your treatment goals before deciding whether an oral SERD makes sense for you.
How well does imlunestrant work?
The phase 3 EMBER-3 trial included 874 people with estrogen receptor-positive, HER2-negative advanced or metastatic breast cancer. Everyone had previously received an aromatase inhibitor, and about 60% had also taken a CDK4/6 inhibitor.
The results that led to FDA approval focused on 256 people whose tumors had an ESR1 mutation. They received either imlunestrant or another endocrine therapy chosen by their doctor, such as exemestane or fulvestrant.
The median progression-free survival was:
- 5.5 months with imlunestrant
- 3.8 months with fulvestrant or exemestane
Progression-free survival is the amount of time the cancer stays under control before it grows or spreads. A median is the midpoint, which means some people had shorter responses and others had longer ones.
During the study, imlunestrant lowered the risk of cancer progression or death by 38%. Tumors shrank in about 14% of people with measurable cancer who took imlunestrant, compared with about 8% who received standard endocrine therapy.
Why can a few added months of disease control matter?
Those added months mean more time when the cancer is stable and causing fewer problems. That may translate to more time feeling well enough to keep up with family, hobbies, work, travel, and other parts of life that matter to you.
Study results are averages across many people. While your personal response may be shorter than what researchers found in clinical trials, there’s also a chance you could have a better quality of life for much longer.
How soon will you know when treatment is working?
Your first scan will usually happen about two or three months after you start treatment. It may show that the tumors have shrunk or stayed the same size. Both can be meaningful signs that imlunestrant is controlling the cancer.
You may also notice changes in how you feel during the first month or two. Your symptoms, blood tests, and scans all help your care team see how well the treatment is working.
How do you take imlunestrant?
You take two tablets once a day. Take both:
- At about the same time each day
- On an empty stomach
- At least two hours before food or one hour after food
- Whole, without chewing, crushing, or splitting them
If you throw up after taking imlunestrant, wait and take your next dose at the usual time the following day. Follow the same advice if your dose is six or more hours late.
Premenopausal and perimenopausal women, as well as men, should also take a medicine called a GnRH agonist to lower hormone production.
Plan to stay on treatment for as long as imlunestrant controls the cancer and the side effects stay manageable.
What side effects can you expect?
Most people in the trial were able to stay on treatment without big issues. But like all medications, imlunestrant can cause unwanted symptoms.
Common side effects are:
- Muscle, joint, or bone pain
- Fatigue
- Diarrhea
- Nausea
- Constipation
- Belly pain
Diarrhea can be a bigger problem with imlunestrant than some other SERDs. Let your care team know early if it happens to you. They can help control your symptoms and prevent dehydration.
While on imlunestrant, blood tests may also show:
- Lower blood cell counts
- Changes in liver enzymes
- Lower calcium
- Higher cholesterol or triglycerides
About 5% of people in the trial stopped imlunestrant because of side effects, and few needed a lower dose. Your doctor can adjust, pause, or stop treatment if side effects become a problem, so let them know about any symptoms that bother you.
What tests and follow-ups will you need?
Your care team will usually see you about once a month when you start imlunestrant. Visits may become less frequent once treatment is going smoothly. You’ll also have scans every few months to check how well the drug is working.
Regular tests will check your:
- Blood cell counts
- Liver function
- Calcium and other body salts
- Cholesterol and triglycerides
Call your care team if a new symptom appears or an existing one gets worse between visits. Side effects are usually easier to treat when caught early.
Is it safe? Are there health conditions or medicines to consider?
Imlunestrant is generally well tolerated.
Some medicines and supplements can affect how your body processes it. Give your oncologist and pharmacist a full list of everything you take, so they can check for drug interactions.
You may need a lower dose if you have moderate or severe liver problems.
Imlunestrant can harm a fetus. Your care team may suggest you take a pregnancy test and birth control during treatment and for one week after your last dose. Men with partners who could become pregnant should also use birth control during this time.
Avoid breastfeeding during treatment and for one week after your final dose.
Can imlunestrant be combined with other breast cancer drugs?
EMBER-3 also studied imlunestrant with abemaciclib, a CDK4/6 inhibitor.
The median progression-free survival was:
- 9.4 months with imlunestrant plus abemaciclib
- 5.5 months with imlunestrant alone
This part of the study included people with and without ESR1 mutations.
Combining drugs may control the cancer for longer, but it can also add side effects. Abemaciclib commonly causes diarrhea, so your care team will watch for and help you manage this symptom.
Imlunestrant is currently FDA-approved on its own for ESR1-mutated cancer. Ongoing research may help doctors learn more about when combination treatment works best.
Will insurance cover imlunestrant? Is there a generic?
Coverage depends on your insurance plan. Even when imlunestrant is covered, you may have a high copay or need to meet a deductible (the amount you pay before insurance kicks in).
Ask your cancer center for help with costs. Many have specialty pharmacy teams or financial counselors who may be able to:
- Submit prior authorization paperwork
- Appeal a denial
- Check patient assistance programs
- Look for grants or copay support
There’s currently no generic version of imlunestrant.
What comes next for oral SERDs?
Oral SERDs give doctors another way to treat advanced or metastatic breast cancer when earlier hormone therapy stops working.
Researchers are studying imlunestrant with other targeted drugs and in people with earlier-stage breast cancer. They’re also looking at whether switching to a SERD after several years of hormone therapy could help delay or overcome treatment resistance.
As more oral SERDs become available, doctors will learn which drugs and combinations work best for different tumors. For now, ESR1 testing helps identify the people most likely to benefit from imlunestrant.
