Real-world evidence involves gathering information about how a drug performs in routine clinical practice, outside of clinical trials. Knowing the real-world impact of a drug can help patients and their doctors make more informed decisions about their treatment.
In this episode of Breast Cancer Breakthroughs, we speak with Komen Scholar Donald McDonnell; Ph.D., medical oncologist Maryam Lustberg, M.D., M.P.H.; and METAvivor President Kelly Shanahan, M.D., as they talk about the real-world evidence and clinical use of oral selective estrogen receptor degraders (SERDs), how these drugs have impacted individuals living with metastatic breast cancer and what we can expect to see next.
Impact of Oral SERDs on Patients
If a cancer is estrogen receptor positive (ER+), its growth is driven by the estrogen receptor. SERDs are drugs that bind to the estrogen receptor in the cancer cell, which causes degradation or break down of the receptor.
Prior to 2023, fulvestrant was the only SERD used in the clinic. Originally FDA approved in 2002, fulvestrant is given as an injection. But, traveling to the clinic for regular injections is not always easy for patients.
Also, many patients with ER+, HER2- metastatic breast cancer (MBC) have progression (where the cancer grows or spreads) while on standard of care, which consists of endocrine/hormone therapy (such as an aromatase inhibitor or fulvestrant) used in combination with a CDK4/6 inhibitor.
The EMERALD clinical trial tested a new oral SERD – elacestrant. FDA-approved in 2023, this treatment is shown to be effective in individuals with ER+, HER2- metastatic breast cancer who progressed on standard of care and had developed an estrogen receptor 1 (ESR1) gene mutation, which ‘turns on’ the estrogen receptor and is what can drive cancer progression. Elacestrant works by binding to the estrogen receptor and causing its degradation (break down). It also offers the convenience of a pill that can be taken at home.
But research on elacestrant didn’t stop with its FDA approval.
Dr. Shanahan, who has been living with MBC since 2013 says, “I think it’s incredibly important that we not only do rigorous clinical trials, but we also gather information from people taking these drugs out in the real world.”
“Pharmaceutical companies want the cancer Olympians in their clinical trials,” Dr. Shanahan continues. “But once that drug is approved and it gets out in the wild, then [everyday] people are using it—people who are older, people who are sicker, people who have other health conditions, people who’ve been on multiple lines of therapy.”
To gather real-world evidence on elacestrant, researchers conducted and published two separate studies in 2025 and 2026. Evidence was collected from people with ER+, HER2-, ESR1-mutant MBC that had progressed on at least one prior line of therapy.
Real world analyses measuring time to next treatment (TTNT) showed that patients remained on elacestrant treatment for approximately 7.9 to 8.8 months in several clinical subgroups. Longer TTNT was generally observed when elacestrant was used earlier in the treatment course, and clinically meaningful treatment response was also observed in people with coexisting PI3K-pathway mutations, an additional driver of cancer growth and spread.
“Both studies [supported] the EMERALD clinical trial progression-free survival data that were documented, really giving us additional comfort and confidence that when an ESR1 mutation is present in a tumor, this is a good opportunity to utilize this type of oral SERD therapy,” says Dr. Lustberg.
Let’s Keep Research Momentum Strong
Another oral SERD, imlumnestrant, was FDA-approved in 2025 for ER+, HER2-, ESR1-mutant advanced or metastatic breast cancer who had progressed on at least one line of endocrine therapy, following favorable results from the EMBER-3 clinical trial.
And efforts are underway to further expand the range of available treatment options for this patient population. These include clinical trials on other oral SERDs and combining them with targeted treatments. “There are exciting phase three trials that are in progress or have reported out, and these [may] lead to additional drugs being approved in the oral SERD category,” says Dr. Lustberg.
Dr. McDonnell notes that new treatments bring not only more options for patients but the ability to better tailor treatment to the individual patient. “I think that it is clear right now that the four or five SERDs that have or will be approved have completely different clinical profiles and there will be some precision medicine approaches used here to actually decide which drugs are best for what patients,” he explains.
When given the option by her oncologist, Dr. Shanahan opted to take elacestrant. “I was doing a lot of traveling, doing advocacy for METAvivor and my Fulvestrant injections just were not going to work,” she says. Because of research, she could get the treatment she needed while living life on her own terms.
Dr. Shanahan continues to look forward to what the future holds in this space. “I’m really excited about the oral medications. The oral SERDs, the CERANs, the PROTACs, the other alphabet soups out there and the targeted drugs for those of us that have mutations, especially in the PIK3CA pathway.”
“A lot of these trials have looked at the oral SERDs by themselves following other treatments,” Dr. Shananhan continues. “And yeah, they’ve been good, but I think they’re going to be way better in combination with other drugs. There are trials like ELEVATE and ELECTRA out there in the oral SERD space that I’m looking forward to [additional] data being presented in the next year or two.”
Individuals living with MBC, like Dr. Shanahan, have played a prominent role in making sure the patient’s voice is heard in research. But the work isn’t finished.
“As good as clinical trials are, they can be better. And one way that clinical trials can be better is for the sponsors of the clinical trials to include patients and trained patient advocates in the design of the clinical trials from the get-go,” she says. “We can help design trials that are more attractive to patients. We can help recruit patients and help retain patients in trials. Bring us in early and often. We’re the reason you built the table, so give us a seat at it.”
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Content covered in the Breast Cancer Breakthroughs educational series may be an emerging area in research or technology. This information is being provided for educational purposes only and is not to be construed as medical advice. Talk with your doctor about what is right for you.
For more information on clinical trials or if you need support as you go through treatment, the Komen Patient Care Center can help. Please contact the Komen Breast Care Helpline at 1-877 GO KOMEN (1-877-465- 6636) or email helpline@komen.org.
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