Analysis of data from the I-SPY 2 clinical trial showed that race did not significantly affect several key measures of breast cancer treatment outcomes, including pathologic complete response and event-free survival, according to results presented at the San Antonio Breast Cancer Symposium, held December 7–10, 2021.
“Breast cancer treatment and management is constantly evolving with advancements in immunotherapy leading the way. However, there remains a persistent mortality gap between white and Black women with breast cancer,” said lead author Beverly Kyalwazi, BS, a medical student at the University of Chicago Pritzker School of Medicine. According to recent estimates, Black women with breast cancer are about 40 percent more likely to die of the disease than white women.
Previous research has shown that pathologic complete response is a strong predictor of distant recurrence-free survival. In this study, Kyalwazi, working in conjunction with senior authors Olufunmilayo Olopade, MD, FAACR, director of the University of Chicago Center for Clinical Cancer Genetics and Laura Esserman, MD, MBA, director of the University of California San Francisco Breast Care Center and the principal investigator of the I-SPY 2 trials, aimed to assess whether racial disparities exist in the achievement of pathologic complete response. As a secondary aim, the researchers studied the association between racial groups and 28 expression signatures related to immune cell types, checkpoint inhibitor targets, and immune signaling pathways.
Final study data included 974 patients; follow-up data was available for 907, with a median follow-up time of 4.4 years. Eighty-one percent of the women were white; 12 percent were Black; and 7 percent were Asian. Study participants came from 10 treatment arms of the I-SPY 2 trial. They had been randomly assigned to either standard neoadjuvant therapy with paclitaxel followed by doxorubicin and cyclophosphamide or an investigational drug (neratinib, veliparib and carboplatin, trebananib, ganitumab, MK2206, pertuzumab, TDM1 and pertuzumab, ganetespib, pexidartinib, or pembrolizumab) with paclitaxel. The researchers analyzed associations of race with pretreatment grade, subtype, and residual burden class, and used logistic regression to evaluate pathologic complete response and event-free survival in all racial groups.
The study showed that pathologic complete response rates did not significantly differ by racial groups. There were also no significant differences in event-free survival or residual cancer burden.
Among women who did not experience pathologic complete response however, HR-positive/HER2-negative breast cancer showed the greatest survival disparity between Black women and white women, with Black women almost twice as likely to experience mortality than white women. This finding was consistent with other recent research on this topic by Olopade and may suggest that biological factors may have resulted in a lack of response to therapy.
“It is critical for us to work to understand and address this underlying disparity and develop interventions to improve outcomes for women who do not experience pathologic complete response. An improved knowledge of how tumor biology predicts response could help researchers develop novel approaches that not only target the tumor and immune microenvironment but also take into account the individual characteristics of the patients to help guide clinical trial design,” said Olopade.
Patients with high-risk Mammaprint gene expression were eligible to participate in the I-SPY 2 trial. Among the 28 expression signatures evaluated, only three were differentially expressed among racial groups for the HR-positive/HER2-negative breast cancer subtype: IFN module, mitotic score, and ER/PR module. Kyalwazi said further research would be necessary to understand how these differences could potentially influence disparities in breast cancer outcomes and design of innovative interventions to close the mortality gap.
Overall, Kyalwazi said the similar outcomes in pathologic complete response and event-free survival for women of all races indicates that tumor molecular subtype is a more significant factor in breast cancer survival than race.
“This is reassuring because it helps us to know that biomarker-informed therapies should work for patients across all racial groups with equal access to quality care,” she said. “These results demonstrate that when women are able to access the appropriate, effective therapies based on their tumor profiles, achievement of pathologic complete response and survival is independent of race.”
The results underscore the importance of enrolling more Black women into breast cancer clinical trials to ensure that they have access to the full range of biomarker-informed cancer therapeutics, she said.
“As long as racial disparities exist, race will continue to be a part of discussions regarding breast cancer,” Kyalwazi said. “Understanding that race is less likely than tumor biology to predict response to therapy places more of a focus on strategies to increase access to quality cancer care among women underrepresented in clinical trials.”
“We are committed to ensuring access to all women in the I-SPY TRIAL, especially women who are traditionally underrepresented in trials. Our trial sites reflect both the geographic and racial diversity of the country. Women of color have a higher mortality rate from breast cancer, and trials with personalized therapies and full genomic profiling will help us to improve the outcomes for all women,” said Esserman.
A limitation of the study was the relatively small number of self-reported Black and Asian patients. Kyalwazi noted that additional analysis will include 1,000 more I-SPY participants, 12 percent of whom are Black. Also, study data did not capture socioeconomic differences or patient comorbidities that could have influenced response to treatment.