Around 40% of breast cancers, especially those that are hormone receptor-positive (HR+) and HER2-negative (HER2-), begin with a change or mutation in the PIK3CA gene. This mutation happens only in cancer cells and not in healthy cells. Like a switch stuck in the “on” position, a PIK3CA mutation signals cancer cells to keep growing, even when they shouldn’t. That’s because it affects the PI3K pathway, a key communication system inside healthy cells that normally helps control growth and survival. When the PI3K pathway becomes overactive because it has a mutation, it can cause cancer cells to grow and spread faster and become more difficult to treat.
Today, doctors test metastatic HR+ breast cancers (MBC) for PIK3CA mutations and use targeted drugs called PI3K inhibitors to try to stop this from happening, but these drugs present challenges for patients, including adverse side effects. Through clinical trials, researchers are seeking new, innovative therapies that will target the PI3K pathway, lessen side effects and improve outcomes for these patients.
In this episode of Breast Cancer Breakthroughs, for the first time ever, we take an in-depth look at the PI3K pathway, exploring its role in breast cancer and the groundbreaking research that is bringing in the next generation of PI3K inhibitors. We speak with Komen Scholar Carlos Arteaga, M.D., and medical oncologist Komal Jhaveri, M.D., about how the PI3K pathway impacts breast cancer, the challenges in targeting it and clinical trials offering better treatment options. We also hear from Komen Advocate in Science Thelma Brown about the importance of demystifying clinical trials and making them more accessible to all patients.
The ReDiscover-2 Clinical Trial
While PI3K pathway inhibitors have proven to be effective in improving outcomes for those with PIK3CA mutations, many patients suffer from their side effects. The phase 3 ReDiscover‑2 clinical trial is one trial addressing this issue in treatment for people with HR+/HER2‑ metastatic breast cancer (MBC) who have a PIK3CA mutation and were treated with a CDK4/6 inhibitor in the past. The trial is testing a new drug called RLY-2608, which is designed to minimize the adverse side effects seen with other PI3K inhibitors.
“The ReDiscover-2 trial is asking a critical question for those with PIK3CA mutations, and that is, can we control breast cancer longer, but do it with fewer side effects that impact daily life?” says Thelma. “Because it’s not just about extending survival; it’s about extending quality of life.”
Thelma, a two-time breast cancer survivor, was inspired to become a research advocate by her own diagnosis as well as those of several family members, including two sisters who died from MBC. Through these experiences, Thelma transformed her survivorship into advocacy, championing better science, greater equity and renewed hope for patients. And while she has not personally been treated with PI3K inhibitors, Thelma finds reassurance in knowing that studies like ReDiscover-2 are bringing patients, especially those in the MBC community, closer to promising outcomes.
“This trial represents hope,” she says. “Every new option that comes from research gives patients another chance, another path forward. And for those with limited treatment options, that means everything.”
Improving Access to Clinical Trials
Thelma has dedicated her life to ensuring clinical trials like ReDiscover-2 are accessible and beneficial to all patient populations. People living with MBC need better access to clinical trials because these studies are not just experimental or mysterious; they are becoming a part of standard, high-quality treatments for breast cancer. Unfortunately, many patients don’t know this, because clinical trials are often explained in confusing, technical language.
To complicate things further, doctors don’t always bring up clinical trials with patients, sometimes because of personal bias or limited institutional support, so patients often don’t know to ask about them. These challenges are further compounded for those that live in under resourced communities or don’t live near major hospitals.
To help overcome these barriers, information about clinical trials should be easy to understand and widely available. As Thelma explains, people should feel confident and informed enough to ask their doctors about clinical trials, understanding that they might be a valuable or even routine part of their care, and not a last resort.
“In some arenas, people think of clinical trials as part of standard of care, and I think that is how it should be thought of, and how it should be communicated to patients,” Thelma says.
Expanding access to clinical trials helps ensure that all patients can benefit from the latest treatments and advances in breast cancer care. As Thelma explains, access to research for MBC is critical, as we are still losing about 40,000 lives a year.
“We can’t just develop new drugs. We have to make sure they reach all patients, especially those who are underserved in rural communities,” she says. “Research is hope, but it’s only hope if it reaches everyone. That’s the future that’s worth fighting for, and that’s what I’m fighting for.”
Learn more about PI3K inhibitors for metastatic breast cancer.
Check out the ReDiscover-2 trial fact sheet.
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cancer treatment and technology coming soon for patients.
If you’d like more information about choosing a clinical trial, BreastCancerTrials.org, in collaboration with Susan G. Komen®, offers a custom matching service to help find clinical trials that fit your needs.
Check out our Questions to Ask Your Doctor reference for additional guidance in finding a clinical trial.
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