Patient race did not significantly impact the percentage of patients who had no detectable disease in biopsied/surgically removed tissue after treatment (known as pathologic complete response) or event-free survival in patients with high-risk breast cancer who received presurgical chemotherapy.
However, disparities existed for a subgroup of women who did not achieve a pathologic complete response, according to data presented at the 2021 San Antonio Breast Cancer Symposium.
According to the National Cancer Institute Surveillance, Epidemiology, and End Results Program, Black women with breast cancer are approximately 40% more likely to die from their disease than White women with breast cancer.
“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,” lead study author Beverly Kyalwazi, a medical student at the University of Chicago Pritzker School of Medicine, said in a press release.
The phase 2 I-SPY 2 platform trial included 990 women with stage 2 or 3 breast cancer at high risk for early recurrence who were randomized to either standard chemotherapy alone consisting of paclitaxel then anthracycline versus standard chemotherapy plus an investigational agent. After a median follow-up of 4.4 years, this analysis evaluated whether pathologic complete response was affected by the race of the patient.Additionally, the investigators assessed variations in immune-related gene signature expression, which can be used to predict response to treatment and breast cancer outcomes.
“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,” senior study author Dr. Olufunmilayo Olopade, director of the University of Chicago Center for Clinical Cancer Genetics, said in a press release. “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.”
There were 16 patients excluded from this analysis because they were a part of a racial group with less than 10 patients on the trial, for a total of 974 evaluated for pCR; 907 were evaluated for event-free survival (time after primary treatment ends that the patient remains free of certain complications or events that the treatment was intended to prevent or delay). Of the pathologic complete response-evaluable patients, the self-reported racial groups included:
- 786 White patients (81%)
- 120 Black or African American patients (12%)
- 68 Asian patients (7%).
Ethnicity was not looked at in this analysis. Race had no significant associations with pre-treatment Scarff-Bloom-Richardson grade, which helps determine how differentiated cancer is; expression-based subtypes; or hormone receptor (HR)/HER2-defined subtypes.
The study results demonstrated that pathologic complete response rates did not differ significantly by racial group. Residual cancer burden class distribution also did not show any significant difference, nor did Scarff-Bloom-Richardson grade. Thirty-two percent of White patients achieved pathologic complete response, as did 30% of Black or African American patients and 32% of Asian patients.
The investigators also observed that event-free survival was not associated with patients’ race.
Divides Exist in Patients Without Pathologic Complete Response
But for patients who did not achieve a pathologic complete response, there were significant differences in event-free survival. Black or African American patients had more significant rates of disease recurrence or mortality than White patients. Furthermore, Black patients with HR–positive, HER2-negative disease who did not achieve pathologic complete response had higher recurrence than White women.
There were no statistically significant differences for patients with triple-negative, HR–positive, HER2-positive, or HR–negative, HER2-positive breast cancer.
“It’s important to note that among these sub-analyses, our P value … decreased because we had a smaller sample size,” Kyalwazi said in her presentation. P values determine how strongly correlated a potential cause is with an outcome.
The similar pathologic complete response and event-free survival outcomes among women of different races demonstrated that tumor molecular subtype is more significant in breast cancer survival than race, according to Kyalwazi.
“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,” Kyalwazi said in the release. “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.”
When looking at the connection between racial groups and 28 expression signatures related to immune signaling pathways, immune cell types and checkpoint inhibitor targets, investigators observed that the interferon module signature in Black patients with HR–positive, HER2-negative breast cancer was significantly different from White patients. In the same subtype, Asian patients had higher expression of the estrogen/progesterone module compared with Black patients, and Black patients had a higher mitotic score, which rates how aggressive tumor cells are, than Asian patients.
“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 Dr. Laura Esserman, director of the University of California, San Francisco Breast Care Center and the principal investigator of the I-SPY 2 trials.
Kyalwazi noted in her presentation that the women on the I-SPY 2 trial have high-risk breast cancers and differ from the general population of women with breast cancer. This trial included a small number of self-reported Black and Asian patients compared with self-reported White patients, although this reflects the United States population racial demographics. Lastly, patient socioeconomic factors and comorbidities, such as diabetes and hypertension, were not considered in this analysis.
“As long as racial disparities exist, race will continue to be a part of discussions regarding breast cancer,” Kyalwazi said in the release. “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.”
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