RxPONDER Analysis Reveals Racial Disparities in HR+/HER2– Breast Cancer

Yara Abdou, MD

An analysis of race and clinical outcomes among patients enrolled in the phase 3 RxPONDER trial (NCT01272037) found that non-Hispanic Black patients with hormone receptor (HR)–positive/HER2-negative breast cancer were more likely to have worse outcomes vs non-Hispanic White, Asian, and Hispanic patients. However, it is not yet possible to make definitive conclusions about racial differences in treatment benefit due to a limited number of events in the non-Hispanic Black cohort, according to Yara Abdou, MD.

In the analysis presented at the 2022 San Antonio Breast Cancer Symposium, investigators evaluated 4048 patients enrolled on the study with HR-positive/HER2-negative breast cancer, 1 to 3 positive lymph nodes, a recurrence score of no more than 25, and known race/ethnicity. Findings showed that non-Hispanic Black patients (n = 248) experienced a 5-year invasive disease-free survival (iDFS) rate of 87.2% vs 91.5% in non-Hispanic White patients (n = 2833; unadjusted hazard ratio, 1.39; 95% CI, 1.01-1.91; P = .04). The 5-year iDFS rates for non-Hispanic Asians and Hispanic patients were 93.9% and 91.4%, respectively.

“Our study, similar to prior studies, has shown racial disparities in breast cancer particularly in the HR-positive subgroup,” Abdou said. “This highlights the need for us to further investigate ways to improve outcomes for minority women with breast cancer, starting with an increase in direct representation of minority woman in clinical trials. That way, we're able to better understand cancer disparities and eventually improve outcomes.”

In an interview with OncLive^®, Abdou discussed the racial and clinical analysis of the RxPONDER trial, the need to further investigate the factors that create racial disparities in breast cancer, and the importance of enrolling minority populations onto clinical trials. Abdou is a medical oncologist with the UNC Lineberger Comprehensive Cancer Center in Chapel Hill, North Carolina.

OncLive^®: What was the goal for investigating the relationship between race and clinical outcomes in the RxPONDER trial?

Abdou: Racial disparities in breast cancer outcomes continue to be a major health-care challenge. Therefore, further studies are needed to improve outcomes for minority women with breast cancer. Our study, in particular, focused on determining whether there were any racial and ethnic disparities in the RxPONDER trial. As a reminder, the RxPONDER trial established the clinical utility of the 21-gene recurrence score in HR-positive/lymph node–positive breast cancer.

Objectives of our study included looking at clinical and pathologic characteristics by race, recurrence score distribution by race, and outcomes by race, and then determining whether there was any race effect on treatment benefit.

Could you expand on the key findings from this analysis? Did recurrence score, treatment arm, age, or grade affect outcomes?

The study included approximately 4048 women from the RxPONDER trial. In regard to clinical and pathologic characteristics, we did not find any significant differences in the number of positive lymph nodes, tumor size, or recurrence score distribution across all cohorts. However, tumor grade was found to be significantly different, and our non-Hispanic Black patients were found to have fewer low-grade tumors and more high-grade tumors compared [with] non-Hispanic Whites.

In regard to outcomes, non-Hispanic Black patients had worse iDFS compared [with] non-Hispanic Whites. They were also noted to have worse distant relapse-free survival compared [with] non-Hispanic Whites. Even when we adjusted for recurrence score, treatment arm, age, and grade, [this] did not alter the impact of race, suggesting that race was independently prognostic in that cohort of patients.

Were there any other notable outcomes?

Higher body mass index [BMI] is a known contributing factor to worse outcomes in breast cancer. We looked at our cohort in RxPONDER, and we noted that non-Hispanic Black patients had higher BMI scores compared [with other racial groups. However, when we adjusted for the BMI factor, it appeared that the BMI did attenuate the race effect on survival outcomes but did not completely eliminate it, suggesting that BMI is not the only factor contributing to the noted worse outcomes.

What are the practical implications of these findings?

At this time, there is no compelling evidence to suggest that the recurrence score is not applicable in racial [or] ethnic minorities. Therefore, the overall results of the RxPONDER trial should be applicable in all racial cohorts.

What are investigators doing to improve diversity and inclusion in clinical trials for breast cancer?

Diversity and inclusion in clinical trials is extremely important. There are a lot of efforts being made in that regard through the National Cancer Institute and large cooperative groups, such as SWOG and Alliance. Ways to [improve diverse enrollment include] less stringent eligibility criteria, which could discriminate against certain cohorts in clinical trials. Other ways to increase diversity in clinical trials are by improving cultural awareness amongst health-care professionals and involving our patient advocates in the design of our clinical trials to recruit and retain minority woman with cancer.

What next steps do you hope to see in disparities research?

The next step for research is to further investigate the underlying causes of the disparities that we noted. We are going to investigate biological and non-biological factors that could be contributing to the underlying disparities, including social determinants of health.

Other contributing factors could be endocrine therapy adherence, and endocrine therapy resistance. These are all things we're planning on looking into in the future to further investigate why we're seeing these disparities in the RxPONDER trial.

Editor’s note: Dr Abdou reports serving in an advisory/consulting role with AstraZeneca and Exact Science, and honoraria for CME activities with MJH Holdings, MDEdge, and Clinical Care Oncology.

Reference

Abdou Y, Barlow WE, Gralow JR, et al. Race and clinical outcomes in the RxPONDER trial (SWOG S1007). Presented at: 2022 San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, TX. Abstract GS1-01.