Estrogen receptor-positive (ER+)/HER2-negative (HER2-) breast cancer is one of the most common types of breast cancer, making up 70-80% of diagnoses. While the five-year relative survival rate for these patients is more than 95%, hormone receptor-positive breast cancers can recur (come back) more than 10 years after diagnosis, meaning there is an ongoing long-term risk of recurrence.
For many patients, this means living with constant stress and anxiety, even long after their treatments are finished. Even after completing several years of treatment, those who face the risk of recurrence may feel like they have run a marathon but cannot cross the finish line.
Most ER+/HER2- breast cancers need estrogen to help them grow. Patients are usually treated with hormone-blocking medicine (endocrine therapy) for several years to help reduce the risk of recurrence. Through recent advances in clinical trials, researchers have discovered targeted treatments that can block estrogen receptors on the surface of cancer cells and shut them down. While these treatments work well initially, cancer cells can adapt and often find ways to outsmart them.
“Improving outcomes for patients who are at the highest risk of recurrence with ER-positive disease has been something we’ve long been trying to do,” Sara Tolaney, M.D. says.” Dr. Tolaney is a medical oncologist at Dana-Farber and an investigator of the ELEGANT clinical trial.
The ELEGANT Clinical Trial
Researchers of the ELEGANT clinical trial are exploring a simple, but powerful idea: what if these patients receive a newer and different hormone therapy that can completely wipe out the cell’s estrogen receptors before the cancer has a chance to come back?
ELEGANT is an international, randomized, open label, phase 3 study sponsored by Stemline Therapeutics. To be part of this study, participants must have early-stage ER+/HER2- breast cancer that has spread to nearby lymph nodes. They must also have received 24 to 60 months of standard hormone therapy, with or without a CDK4/6 inhibitor.
For this study, participants will be divided into two groups, with one receiving an oral selective estrogen receptor degrader (SERD) called elacestrant and the other continuing treatment with their usual hormone therapy. Unlike past hormone therapies that only block the estrogen receptor on the surface of the cancer cell, elacestrant helps break the estrogen receptor down completely. Without the estrogen “fuel” that cancer cells need to grow, they weaken, and some eventually die, which may potentially avoid the spread of breast cancer. Compared to currently available hormone therapy, elacestrant may also result in fewer hot flashes and improved bone health.
For ELEGANT, the team will evaluate participants over a five-year period for several factors including whether they remain cancer-free, if any experience recurrence and how well they tolerate treatment. The primary goal of the ELEGANT clinical trial is to determine whether staying on current hormone treatment or switching to elacestrant can lower the chance of recurrence and improve long-term outcomes for these patients. The study also aims to monitor the bone density of participants and assess their quality of life through questionnaires. Researchers will also assess how breast cancer is impacting participants’ daily lives and how they feel after receiving the study treatment.
Sequencing as a Treatment Strategy
What makes the ELEGANT clinical trial unique in its approach is that it isn’t just about trying a new drug. It’s about the timing. This “sequencing strategy” could be a key factor in changing outcomes for patients.
“Oral SERDs seem to be more effective than standard endocrine therapies, which gives us a lot of interest in trying to think about the sequencing strategy, when people have had a couple years of endocrine therapy and then switch them on to a potentially better agent,” Dr. Tolaney says.
An earlier intervention could mean a lower risk of recurrence.
Harnessing the Benefits of Oral SERDs
Because ER+/HER2- breast cancer can be long-term for many, it is also critical to have a treatment that is tolerable. Elacestrant has been approved by the FDA for treatment of metastatic breast cancer (MBC), so its safety profile and side effects are already well known. For those living with breast cancer, oral SERDs like elacestrant are a more convenient option that offer flexibility.
“From a quality-of-life perspective for our patients, these drugs could be really beneficial, not just because they’re more efficacious, but also potentially better tolerated than the current standard of care,” Dr. Tolaney says.
Some people experience mild GI side effects from elacestrant, but overall, it is generally well tolerated. Elacestrant also preserves bone health better than other standard hormone therapies like aromatase inhibitors (AIs). According to Dr. Tolaney, AIs often deplete estrogen levels in the body, and estrogen is essential for bone health. For this reason, AIs sometimes lead to risks of osteoporosis and fracture.
“There is some suggestion that elacestrant can have agonistic effects on bone and therefore may protect against bone loss,” Dr. Tolaney says.
Why Clinical Trials Like ELEGANT Matter
Studies like ELEGANT illustrate how clinical trials are not a last resort for patients, but a way to explore new options that could lead to better long-term outcomes. For people living with ER+/HER2- breast cancer and dealing with the uncertainty of recurrence, this study offers more than a new drug option. The ELEGANT clinical trial focuses on early care, possibly helping patients stay ahead of recurrence and lowering the chances that they’ll need more aggressive treatments in the future.
Thanks to ongoing research, breast cancer treatment has greatly improved over the years. Today, clinical trials like ELEGANT are opening doors to more options than ever before, giving patients new reasons to feel hopeful about what lies ahead.
Learn more about the ELEGANT clinical trial.
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Menarini-Stemline is a sponsor for the Spotlight on Clinical Trials series and the sponsor of ELEGANT.
