Article

Likelihood of Pathologic CR After Neoadjuvant Chemo is Not Significantly Affected by Race in Breast Cancer

Pathologic complete response and event-free survival was not found to be significantly affected by race among patients with high-risk breast cancer who received neoadjuvant chemotherapy; however, disparities were observed among patients who did not achieve a pCR.

Beverly Kyalwazi, BS

Beverly Kyalwazi, BS

Pathologic complete response (pCR) and event-free survival (EFS) was not found to be significantly affected by race among patients with high-risk breast cancer who received neoadjuvant chemotherapy; however, disparities were observed among patients who did not achieve a pCR, according to findings from a study presented by Beverly Kyalwazi, BS, during the 2021 San Antonio Breast Cancer Symposium.1

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.2

“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,” Kyalwazi, lead author of the analysis and medical student at the University of Chicago Pritzker School of Medicine, said in a statement.3

The phase 2 I-SPY 2 platform trial randomized 990 women with stage II or III breast cancer at high risk for early recurrence 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 pCR was affected by the race of the patient. Additionally, the investigators assessed variations in immune-related gene signature expression.1

“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 pCR,” Olufunmilayo

Olopade, MD, FAACR, senior author and director of the University of Chicago Center for Clinical Cancer Genetics, said in a press release.3 “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 EFS.1 Of the pCR-evaluable patients, the self-reported racial groups included 786 White patients (81%), 120 Black or African American patients (12%), and 68 Asian patients (7%). Ethnicity was not looked at in this analysis. Race had no significant associations with pre-treatment Scarff-Bloom-Richardson grade (P = .49), expression-based subtypes (P = .25), or hormone receptor (HR)/HER2-defined subtypes (P = .09).

The pCR rates did not differ significantly by racial group, with a pCR odds ratio relative to White patients of 1.00 for Asian patients and 0.89 for Black or African American patients.3 Residual cancer burden class distribution also did not show any significant difference (P = .88), nor did Scarff-Bloom-Richardson grade. Thirty-two percent of White patients experienced pCR, 30% of Black or African American patients, and 32% of Asian patients.1

In a univariate Cox model, the investigators observed that EFS was not associated with patients’ race; the hazard ratio relative to White patients was 1.37 for Black or African American patients (P = .13) and 1.10 for Asian patients (P = .73).3

For patients who did not experience pCR, there were significant differences in EFS.1 Black or African American patients had more significant rates of recurrence or mortality than White patients, with a hazard ratio of 1.61 (95% CI, 1.02-2.45; P = .003). Furthermore, Black patients with HR–positive, HER2-negative disease who did not achieve pCR had higher recurrence than White women, with a hazard ratio of 1.95 (95% CI, 1.03-3.73; P = .04).

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 subanalyses, our P value…decreased because we had a smaller sample size,” Kyalwazi said in her presentation.

The similar pCR and EFS outcomes among women of different races demonstrated that tumor molecular subtype is more significant in breast cancer survival than race, according to Kyalwazi.3 “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 a press release. “These results demonstrate that when women are able to access the appropriate, effective therapies based on their tumor profiles, achievement of pCR 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 (P = .007).1 In the same subtype, Asian patients had higher expression of the estrogen/progesterone module compared with Black patients (P = .011), and Black patients had a higher mitotic score than Asian patients (P = .008).

To evaluate the outcomes for this analysis, logistic regression was used for pCR associations, Cox-proportional hazard modeling for EFS, and Chi-Squared test for associations between racial demographics and patient characteristics. The variation in immune-related gene signature expression was examined using ANOVA and the Tukey test.

“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 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.3

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.1

“As long as racial disparities exist, race will continue to be a part of discussions regarding breast cancer,” Kyalwazi said.3 “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.”

References

  1. Kyalwazi B, Yau C, Olopade O, et al. Analysis of clinical outcomes and expression-based immune signatures by race in the I-SPY 2 trial. Presented at: 2021 San Antonio Breast Cancer Symposium; December 7-10, 2021; San Antonio, TX. Abstract GS4-02. https://bit.ly/3dCx4KH
  2. Cancer stat facts: breast cancer. National Cancer Institute Surveillance, Epidemiology, and End Results Program. Accessed December 6, 2021. https://bit.ly/3rMoYHT
  3. Black and White women who received neoadjuvant therapy were equally likely to have pathologic complete response. American Association for Cancer Research. Published December 7, 2021. Accessed December 9, 2021. https://bit.ly/3lGpenM
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