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I-SPY2 Study Finds Tumor Biology Is a More Significant Factor Than Race in Predicting Response to Breast Cancer Treatment


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Data analysis from the I-SPY2 clinical trial found that among women with high-risk breast cancer, race did not significantly affect several key measures of breast cancer treatment outcomes, including pathologic complete response (pCR) and event-free survival. The study, which is being presented by Kyalwazi et al during the 2021 San Antonio Breast Cancer Symposium (Abstract GS4-02), indicates that race is less likely than tumor biology to predict response.

Although mortality rates from breast cancer have been declining, research shows that Black women are 40% more likely to die from the disease than White women, and are twice as likely to die if they are older than age 50. Previous research has shown that pCR is a strong predictor of distant recurrence–free survival.

Given the racial disparities in mortality from breast cancer and the lack of racial demographic data from clinical trials, the aim of this study was to evaluate the association between racial groups and baseline characteristics, including expression-based subtypes and immune signatures, treatment response, and prognosis of patients enrolled in the I-SPY2 trial.  

Study Methodology

The final study data included 974 patients, and follow-up data were available for 907 patients, with a median follow-up time of 4.4 years. Eighty-one percent of the patients were White, 7% were Asian, and 12% were Black.

Chi-square test was used to assess associations between racial groups and pretreatment Scarff-Bloom-Richardson (SBR) grade, hormone receptor/HER2-defined subtypes, intrinsic subtype (defined by BluePrint 80-gene molecular subtyping), and residual cancer burden class. Logistic regression was used to evaluate race association with pCR.

Cox proportional hazard modeling was used to assess the association between racial groups and event-free survival in a univariate setting, adjusting for pCR status. Associations between racial groups and 28 expression signatures related to immune, proliferation, and estrogen receptor and HER2 pathways were analyzed using ANOVA with post-hoc Tukey test in the overall population and in each receptor subtype.

KEY POINTS

  • Among women with high-risk breast cancer, race did not significantly affect several key measures of breast cancer treatment outcomes, including pCR and event-free survival, indicating that race is less likely than tumor biology to predict response.
  • Among women who did not experience pCR, the hormone receptor–positive/HER2-negative subtype showed the greatest survival disparity between Black and White women, with Black women nearly twice as likely to experience mortality than White women.

Results

The researchers found no significant associations between race and pretreatment SBR grade (P = .49), hormone receptor/HER2-defined subtypes (P = .09), or expression-based subtypes (P = .25). pCR rates did not significantly differ by racial groups (odds ratio of pCR relative to White race = 1.00 for Asian patients and 0.89 for Black patients), and no significant differences in residual cancer burden class distribution by race were observed (P = .88).

Event-free survival was not associated with patient racial group in a univariate Cox model (hazard ratio relative to White race = 1.10, P = .73 for Asian patients and 1.37, P = .13 for Black patients). Among the 28 expression signatures evaluated, four were differentially expressed among racial groups within the overall population (F-test P < .05): IFN module, B-cell signature, dendritic cell signature, and Mitotic score. Pairwise comparisons between racial groups with post-hoc Tukey test identified significant differences in IFN module expression between Black vs White patients (P = .019) and dendritic cell signature expression between Asian vs White (P = .047). Among patients in the triple-negative breast cancer subtype, three signatures—dendritic cell signature, macrophage signature, and ERBB2 module—were differentially expressed between Black and White patients (P = .002, .016, and .007, respectively).

"Our analysis demonstrates that among women with high-risk breast cancer, race does not affect subtype specific response rates nor event-free survival. Distribution of subtypes previously shown to be associated with pCR in the I-SPY2 trial did not significantly differ among racial groups, indicating race is less likely than tumor biology to predict response. The decreased expression of immune signatures observed in Black…women with triple-negative breast cancer suggests possible differential sensitivity to immunotherapy plus combination chemotherapy. Tumor immune multiplex studies are underway to further investigate,” concluded the study authors.

Clinical Significance

In a statement following the release of the study, senior study author Olufunmilayo Olopade, MD, FAACR, FACP, Director of the University of Chicago Center for Clinical Cancer Genetics and Global Health, said, “It is critical for us to work to understand and address this underlying disparity and develop novel interventions to improve outcomes for women who do not experience pCR. An improved understanding 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.”

The study’s 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, added lead author Beverly Kyalwazi, BS, a medical student at the University of Chicago Pritzker School of Medicine.

Disclosure: Funding for this study was provided by the Breast Cancer Research Fund and the Pritzker/Northshore Fellowship.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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