Due in part to underrepresentation in clinical trials, Black women in the U.S. are at higher risk from dying of breast cancer than white women. Komen Scholar Bryan Schneider, M.D., trial lead for the EAZ171 clinical trial, is seeking to overcome these disparities in outcomes for Black women with breast cancer by personalizing chemotherapy. Dr. Schneider is director of the Indiana University Health Precision Genomics Program and the Vera Bradley Professor of Oncology at the IU Melvin and Bren Simon Comprehensive Cancer Center.
Dr. Schneider’s previous research found that Black women are more susceptible to a side effect from taxanes, a type of chemotherapy, called taxane-induced peripheral neuropathy (TIPN), a condition that causes pain, tingling and numbness in the hands and feet that can sometimes be permanent. This condition can also impact breast cancer outcomes because people experiencing TIPN are more likely to have their dose of chemotherapy reduced.
“What I think is somewhat original and unique about EAZ171 is a focus not just on the effectiveness of drugs and the potential for cure rate, but also its potential impact on devastating side effects and quality of life.”
Exciting new findings from the EAZ171 trial, which were announced at the 2024 American Society of Clinical Oncology (ASCO) meeting on June 3, found that treatment with the taxane drug paclitaxel is more likely to lead to TIPN than treatment with the taxane docetaxel. These findings are poised to have a major impact on Black women with breast cancer.
New Data to Personalize Treatment for Black Women
The EAZ171 trial had two main goals. The first goal was to determine if certain inherited gene mutations, or biomarkers, could predict the likelihood of developing TIPN. The second goal was to identify the best type of taxane to use to avoid TIPN in Black women with early-stage breast cancer.
The team found that their chosen biomarkers were not able to predict the likelihood for developing TIPN, which may have been due to a small sample size or other biological and clinical factors that may be involved in promoting TIPN. However, they did find that treatment with the taxane paclitaxel led to more TIPN than docetaxel, suggesting that docetaxel may be a better option for Black women with breast cancer.
Dr. Schneider explained that these results will have an immediate impact on patients.
“Making a treatment decision is a very personalized decision, both a function of the disease type but also the patient’s wishes, goals, concerns, and expectations. So, I think this just adds a really nice extra piece of data we can use to counsel our patients to best serve them. I do think this is one of the very few prospective trials really focusing on this question and in my opinion, offers up some of the best data in this venue to date,” says Schneider.
Groundwork for the Future
Based on the findings of the EAZ171 trial, Dr. Schneider’s team is already at work to take the next steps to tackle the problem of TIPN in Black women.
“Our next steps will be, I think, first to try to bring equity to the equation,” remarks Schneider.
His team is designing a new clinical trial that will incorporate additional biomarkers as well as clinical demographics like obesity, diabetes and other factors to better predict the likelihood of developing TIPN.
He is also enthusiastic about his Komen-funded work looking to understand the causes of TIPN at a mechanistic level. By using white blood cells collected from Black women in the EAZ171 trial, he is hoping to uncover potential causes and treatments for TIPN.
“We’re taking those white blood cells and turning them into little sensory neurons in a test tube.
This allows us now to do a number of experiments on those little neurons so we can understand things that are causing damage to the neurons and also differences in genetic expression and other changes that might help us understand why Black patients get more neuropathy,” explains Schneider.
The innovation of Dr. Schneider and his team highlight the significant progress that can be made when working to understand disparities in breast cancer outcomes. According to Schneider, “[this research] can ultimately lead us to potential targets for drugs to either prevent or treat neuropathy successfully in the future.”
