Despite similar 21-gene recurrence scores, non-Hispanic Black women with hormone receptor (HR)-positive/HER2-negative, lymph node-positive breast cancer had worse outcomes compared to non-Hispanic Whites, Asians, and Hispanics, according to a new study. Presenting at the 2022 San Antonio Breast Cancer Symposium, lead study author Yara Abdou, MD, Assistant Professor at the University of North Carolina at Chapel Hill and Lineberger Comprehensive Cancer Center, highlighted the findings (Abstract GS1-01).
Describing ongoing racial disparities in breast cancer outcomes as a "major health care challenge," Abdou noted that Black women are more likely to die from the disease than non-Black women. In an effort to better understand the differences in tumor biology that contribute to this discrepancy, and subsequently discover new opportunities for intervention that will reduce cancer health disparities, Abdou and colleagues analyzed the clinical outcomes with respect to race and ethnicity in the RxPONDER clinical trial.
The RxPONDER trial aimed to assess the value of the 21-gene recurrence score (RS) in patients with lymph node-positive, HR-positive/HER2-negative breast cancer and the benefit of adjuvant chemotherapy in these patients. Measuring the expression level of a group of 21 genes in the tumor tissue to predict the risk of breast cancer recurrence and the response to therapy, the 21-gene RS genomic test is a critical tool in guiding treatment decisions among women with early-stage breast cancer, according to Abdou.
The study included 4,048 women with HR-positive/HER2-negative breast cancer who had 1-3 positive axillary lymph nodes and RS of 25 or lower, which indicates an intermediate or low risk. Non-Hispanic White, Non-Hispanic Black, Hispanic, and Asian patients represented 70, 6.1, 15.1, and 8.0 percent of the study population, respectively.
Overall, the researchers found that the 21-gene RS were similar across all racial subgroups, with no significant differences in tumor size and in the number of lymph nodes involved. However, non-Hispanic Black and Hispanic patients demonstrated a higher frequency of high-grade tumors (17.7% and 14.1%, respectively) than non-Hispanic White and Asian patients (10.2% and 6.5%, respectively).
Five-year invasive disease-free survival (IDFS) rates, which indicate the percentage of patients who were alive and free of breast cancer or any other type of invasive cancer, were also lower among non-Hispanic Blacks (87%) in comparison to Asians (94%), non-Hispanic Whites (92%), and Hispanics (91%). Non-Hispanic Black patients were also at a 37 percent higher risk of invasive cancer compared to non-Hispanic Whites, after adjusting for age, menopausal status, grade, treatment arm, and RS. Non-Hispanic Black patients also had lower distant relapse-free survival (defined as the time from surgery to the first distant recurrence than non-Hispanic Whites).
In 2020, the RxPONDER trial found that premenopausal women with HR-positive/HER2-negative breast cancer with 1-3 positive lymph nodes and RS of 25 or lower benefited from the use of chemotherapy, while postmenopausal women did not. In this new analysis, Abdou and her co-authors found that race did not predict the relative benefit of adding chemotherapy to endocrine therapy, as the clinical outcome by treatment arm was not drastically different between non-Hispanic Black and non-Hispanic White women for IDFS and DRFS.
After a 12-month follow-up period, nearly all non-Hispanic Black patients (96%) were still on endocrine therapy versus 95 percent of non-Hispanic White patients. The researchers noted this result suggests the differences in long-term outcomes are not likely attributable to lack of treatment compliance among non-Hispanic Black women within the first year, but caution that longer follow-up is needed to confirm this finding.
While noting that the authors "do not definitely know what's driving these disparities," Abdou said, "in my opinion, cancer disparities reflect an interplay among many factors, including biological and non-biological factors." Differences in tumor biology by race, for example, may still be a contributing factor, despite similar genetic recurrence scores, she noted, adding that social and behavioral issues should also be taken into consideration.
"When looking at cancer disparities in hormone receptor-positive breast cancer in particular, endocrine therapy compliance and resistance may play a role," Abdou stated. "Prior research has highlighted lower adherence to ET for Black women. Although in our study we noted that Blacks were just as likely to remain on ET within the first year compared to Whites, longer follow-up is needed to confirm whether treatment adherence was a contributing factor to the noted outcome differences in this study."
As previous research has highlighted, endocrine therapy resistance could be an influence as well, especially in obese patients, said Abdou, adding that this analysis indicated that non-Hispanic Blacks tend to have higher BMI scores. "Therefore, endocrine resistance may be playing a role here. But this data so far is just hypothesis-generating and further studies, including more translational research, are needed to answer this question definitively."
Ultimately, Black women with hormone receptor-positive breast cancer experience the greatest racial disparity in survival among all breast cancer subtypes; a survival gap that appears consistent across studies, Abdou noted.
"Therefore, it is very important for us to continue to focus our research efforts on understanding the underlying causes of these disparities and finding ways to close this devastating gap, starting with a greater representation of minority patients in clinical trials. Underrepresentation of certain groups in a study can make the results less applicable to groups who may benefit the most from the findings," she concluded.
Mark McGraw is a contributing writer.