Black or African-American women with high-risk breast cancer benefit as much from neoadjuvant chemotherapy as White women, according to a new study. That said, among patients who did not benefit from this treatment, Black women with a hormone receptor-positive (HR+)/HER2-negative (HER2-) subtype were nearly twice as likely to experience a recurrence of disease or death from their disease than White women. These findings, from an analysis of data from the I-SPY2 multi-center clinical trial, suggest that tumor-specific cell type might be a more important factor than race in predicting response to therapy.
"In the I-SPY2 trial, race is not significantly associated with achievement of pathologic complete response," said Beverly Kyalwazi, BS, a fourth-year medical student at the University of Chicago Pritzer School of Medicine, who presented findings at the 2021 San Antonio Breast Cancer Symposium. "This indicates that women with high-risk breast cancers are equally likely to experience a survival benefit from receiving targeted neoadjuvant chemotherapy.
"In our sub-analysis looking at patients who did not receive pathologic complete response, significant survival disparities were observed, particularly in HR+/HER2- breast cancer subtype among Black women and they had almost double the recurrence risk of White women," she added.
Kyalwazi noted that the breast cancer mortality disparity between Black women and White women is well-established. Recent estimates show that Black women with breast cancer have a 40 percent greater likelihood of dying from their disease than White women. Yet, the percentage of Black women enrolled in clinical trials for breast cancer is woefully poor, with estimates ranging from 2-9 percent participation.
Kyalwazi said this analysis was designed to evaluate whether I-SPY2 clinical outcomes are independent of race and whether variations in immune-related gene signature expressions could predict pathologic complete and event-free survival. The ongoing I-SPY2 trial is designed to screen promising new treatments targeted to specific types of patients.
"Currently, there are 26 active I SPY-2 clinical trials," Kyalwazi said. "The broad distribution of these sites across the country was one of the motivating factors for us conducting this analysis, especially given the disparities in enrolling diverse patient populations in clinical trials today."
As outlined in her presentation, Kyalwazi said the I-SPY2 trial included women with Stage 2 or Stage 3 breast cancers at high risk for early disease recurrence, who received either standard chemotherapy along with paclitaxel followed by anthracycline or standard chemotherapy plus one of several investigational agents. At specific times during the trial, women would undergo biopsy and imaging. Blood samples also would be drawn to help researchers identify potential prognostic biomarkers and to assess if there is a link between those biomarkers to patient demographics and clinical outcomes.
Some 907 patients were included in this analysis, with a median follow-up of 4.4 years. Some 81 percent of patients self-identified as White, 12 percent Black or African-American, and 7 percent as Asian. The median age of the study participants was 49 years. A patient's ethnicity, such as Hispanic, was not included in the analysis, although ethnic data was collected for potential future analysis.
Aside from race, the researchers looked at breast tumor characteristics that included pretreatment grade and residual cancer burden. Patients with high-risk Mammaprint expression were eligible to participate, allowing researchers to examine molecular subtypes associated with self-reported race.
About 30 percent of White patients, 30 percent of Black patients, and 30 percent of Asian patients experienced complete pathologic response, demonstrating that survival was not significantly linked to self-reported patient race. Among patients in the study, the researchers also could not find any significant difference for event-free survival or residual cancer burden.
For those patients who did not achieve pathologic complete response, however, the researchers did observe a significant survival disparity, with Black or African-American women having a significantly higher rate of recurrence or mortality than White women (HR 1.61; p=0.003).
To further investigate, the researchers looked at patients with residual disease, analyzing four specific receptor subtypes. In particular, women with HR+/HER2- had worse outcomes, with Black women experiencing nearly twice the rate of recurrence and mortality as White patients (HR 1.95, p=0.04).
Among the three other receptor subtypes-HR+/ HER2+, HR-/ HER2+, and triple negative-there was no significant difference in pathologic complete response.
In a press release, Olufunmilayo Olopade, MD, FAACR, Director of the University of Chicago Center for Cancer Genetics and co-senior author of the study, said the analysis suggests that biological factors, rather than race, may have resulted in the 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," she said. "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."
For the second part of their study, Kyalwazi and colleagues examined variations in 28 immune signature expressions across racial groups, signatures related to immune cell types, checkpoint inhibitor targets such as PD1 and PDL1, and immune signaling pathways. Immune signatures are generally considered a predictor of response to chemotherapy and immunotherapy combinations.
In particular, the team focused on HR+/HER2- patients with residual disease-patients who generally have poor outcomes. Out of the 28 immune-related expression signatures, the interferon module signature was significantly higher in Black patients compared to White patients.
Two other signatures-ER/PR receptor module and mitotic score expression-were also differentially expressed among patients with residual disease in the HR+/HER2- subtype. Among Asian patients, the ER/PR receptor module was significantly higher than Black patients, with the mitotic expression signature significantly higher among Black patients compared to Asian patients.
Kyalwazi noted that the study was limited by the small number of self-reported Black and Asian patients included in the analysis compared to the number of White patients, which she said was partly a reflection of the U.S population demographics.
Further analysis of the I-SPY2 data, she said, should include more Black and Asian patients, and also consider patient socio-economic factors or co-morbidities such as hypertension and diabetes, known to be contributors in disease outcomes in hormone receptor-positive patients.
"It's very clear that less than 2 percent of patients are in clinical trials, but when they get into a clinical trial that genomics stratifies, then we're equating some of the confounders that really exclude African-Americans from getting optimal outcomes," Olopade said following the presentation. "So, this is the beginning of this type of analysis and we have to congratulate a medical student for pushing us to look at it because otherwise we would not have looked at it."
Warren Froelich is a contributing writer.