One of the greatest challenges today in treating breast cancer is that tumor cells can evolve and change over time and become resistant to treatment. This treatment resistance is caused by mutations, or changes to the blueprint of a tumor cell’s DNA that allow it to adapt and survive. As a result, a treatment that was working well for a patient suddenly becomes ineffective.
As researchers work tirelessly to develop new drugs that can outsmart treatment resistance, they are also seeking alternative treatment methods that can improve a patient’s quality of life.
In this episode of Breast Cancer Breakthroughs, we speak with Donald McDonnell, Ph.D., research scientist at Duke University and Aditya Bardia, M.D., medical oncologist at Massachusetts General Hospital about the progress researchers are making to stay one step ahead of tumor resistance.
Putting Patients First
Komen Scholar and Advocate in Science Meryl Weinreb knows all too well how breast cancer treatment can dramatically change a patient’s quality of life. As someone who received not one, but three separate diagnoses of different breast cancers, Meryl’s treatment experiences include high doses of chemotherapy, a lumpectomy and radiation.
As a three-time breast cancer survivor for over 35 years, she has also seen how research has shifted to prioritize the patient’s needs. “One of the things about having dealt with cancer over three and a half decades is that I got a front row seat on just how things have improved and evolved and changed over that period of time,” Meryl says.
Today, Meryl is leveraging her past experiences and patient advocacy work to make sure the patient voice is implemented in future research. “I think it’s extremely important that the research we conduct is research that’s going to have the greatest impact on improving outcomes for patients,” she says.
Improving Treatment Options
A promising development for patients was discovered by Dr. McDonnell and his lab, whose innovative work led to the discovery of a new drug that can target genetic mutations in patients with metastatic estrogen receptor-positive (ER+) breast cancer.
When tamoxifen, which had been the standard treatment for metastatic ER+ breast cancer, was no longer effective in killing tumor cells, researchers discovered some tumor cells had adapted by developing an ESR1 mutation, or a mutation in their estrogen receptor gene, which made them resistant to treatment.
Dr. McDonnell and his lab discovered a drug that could bind to the estrogen receptor and break it down, causing the tumor cell to see it as damaged and throw it away. This new type of drug was called a selective estrogen receptor degrader (SERD).
Almost 20 years after Dr. McDonnell’s discovery, the drug now known as elacestrant was tested in the EMERALD clinical trial. As the trial results would show, elacestrant was not only a huge scientific advancement for treating tumors with ESR1 mutations, but also offered patients an improved quality of life with a less invasive treatment option.
At the time of the EMERALD trial, the standard of care for patients with metastatic ER+ breast cancer included hormone therapy delivered via an intramuscular shot.
“Patients were getting the medication as an intramuscular shot twice a month for the first month and then once a month after that, so it was very inconvenient,” says Dr. Aditya Bardia, lead investigator on the EMERALD clinical trial. “The unmet need was a better treatment option in this setting, and something that’s oral.”
Promising Options Ahead
While elacestrant is the first treatment of its kind, according to Dr. Bardia, there are four more promising oral SERDs coming down the research pipeline that are currently being tested in Phase 3 trials. This highlights the growing need for more treatments that will target resistant tumors.
“Bottom line, there is a lot of interest in novel ER agents, given that it was an unmet need, so different research groups and companies are trying to address this unmet need with new drugs,” Dr. Bardia says.
Above all, researchers are seeking new treatments that will not only improve outcomes and progression-free survival for patients but also optimize their quality of life. As Meryl observes, emerging oral drugs like elacestrant can offer patients an effective therapy without the pain and inconvenience of past treatments.
“Many of these new targeted therapies are oral medications,” Meryl says. “Clearly, it’s convenient, and it’s also an improvement of quality of life for patients. No one likes to have to go to the clinic once a month and get a painful injection. So, the option of being able to swallow a pill is fabulous.”
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