SAN ANTONIO — An in-depth analysis of why Black women with breast cancer have worse outcomes than women who are White, Asian, or Hispanic was hailed as “probably one of the most important presentations” here at the San Antonio Breast Cancer Symposium (SABCS) 2022.

The comment was made by breast cancer expert Eric Winer, MD, director of the Yale Cancer Center and physician-in-chief, Smilow Cancer Hospital, New Haven, Connecticut, who welcomed the new findings.

Dr Yara Abdou

Racial disparity in breast cancer outcomes “continues to be a major healthcare challenge,” as current data show that American Black women have 4% lower incidence of breast cancer, but a 40% higher breast cancer mortality than White women, said study presenter Yara Abdou, MD, assistant professor at the University of North Carolina at Chapel Hill and Lineberger Comprehensive Cancer Center.

She reported a new analysis of data from the RxPONDER trial, which was conducted in more than 4000 women with hormone receptor positive (HR)+ and HER2 negative (HER2-) breast cancer and up to three positive lymph nodes.

It showed that 5-year invasive disease-free survival (IDFS) was lower for Black women, at 87.2% vs more than 90% for the other racial groups. Similar results were seen when looking at distant relapse-free survival (DFRS).

Black women had “worse outcomes than White women, independent of recurrence score, treatment arm, and grade,” Abdou said. However, adjustment for body mass index (BMI) “appears to decrease this effect,” she noted. 

Although the difference in outcomes between Black women and others was significant after controlling for age, menopausal status, grade, treatment arm, and recurrence score, that was no longer the case after adding BMI into the analysis, although a numerical difference remained.

Black women were more likely to have high BMI than the women in the other groups. BMI over 30 is considered obese. Among these trial participants, 27% of Black women had BMI of 30-34 and 35% had BMI of >35, compared with only 6% and 2% of Asian women, 21% and 18% of White women, and 22% and 16% of Hispanic women.

Abdou commented that the modifying effect of BMI on the results may indicate that pro-inflammatory markers “might be different in Blacks and Whites.”

When looking at the treatment that women received, Abdou noted that there were differences between the groups in chemotherapy, but that endocrine therapy rates were similar. She said that “at this time, definitive conclusions about racial differences in treatment benefit cannot be made, due to the limited number of events” in the Black cohort.

Abdou noted that Black women were more likely than their white counterparts to accept their treatment assignment, at 93% vs 86% (P = .004), and were slightly more likely to remain on endocrine therapy at 6 months (98% vs 96.6%) and at 12 months (96% vs 94.8%).

So any outcome differences are “less likely attributable to lack of treatment compliance within the first year,” she commented.   

Asked to speculate on what is underlying the differences, she said that there is likely “a compilation of factors, including biological and nonbiological factors,” as well as possible differences in adherence after the first year of treatment, and potentially endocrine therapy resistance.

Black women in the study also had a higher disease grade at study entry, particularly when compared with Asian women (18% Black vs 10% White vs 7% Asian).

Abdou told Medscape Medical News that “we know Black women have more aggressive biology with regards to their breast cancer,” yet there was no difference in recurrence score between Black women and those in other groups. Hence, she thinks that the higher grade is simply “reflecting the biology of the disease” in Black women.

However, Virginia Kaklamani, MD, co-director of the San Antonio Breast Cancer Symposium and leader of the Breast Cancer Program at the UT Health San Antonio Cancer Center, commented to Medscape Medical News that disease grade is “subjective.”

“When you talk to a pathologist and you give them slides, they will grade them differently, so that’s always a concern.” Consequently, she always looks at gene risk scores to “give me the biology of the tumor.”

Reacting to the presentation on Twitter, Puneet Singh, MD, assistant professor, Department of Breast Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, suggested that the researchers “need to really delve into tumor biology and social determinants of health to better understand” the results.

 

Study Details

The RxPONDER trial was designed to evaluate the clinical utility of the 21-tumor gene expression assay (Oncotype DX) in women with HR+, HER2- breast cancer, with 1-3 positive lymph nodes.

Women who had an Oncotype DX recurrence score of 25 or less, which is characterized as low risk, were then randomly assigned to chemotherapy followed by endocrine therapy, or endocrine therapy alone.

As reported at the time by Medscape Medical News, the results showed that the benefit of chemotherapy differed by menopausal status, with postmenopausal women deriving no additional benefit from chemo added onto endocrine therapy, while women who were menopausal did experience a benefit.

For this latest analysis, Abdou and colleagues studied 4048 women from the trial with known race/ethnicity, which included 2833 (70%) non-Hispanic White persons, 248 (6.1%) non-Hispanic Black persons, 610 (15.1%) Hispanic individuals, and 33 (0.8%) Native American/Pacific Islander. (This last group was excluded from the survival analysis because of the small numbers of patients and events).

When looking at outcomes, the results showed that Black women had a 5-year IDFS of 87.2% vs 91.5% in White patients, 93.9% in Asian women, and 91.4% in Hispanic patients.

After adjustment for recurrence score, treatment arm, menopausal status, age, and tumor grade, this translated to a hazard ratio (HR) of 1.37 for Black vs White women (P = .05), and 0.67 for Asian vs White women (P = .05), indicating significant differences; the difference between Hispanic and White women translated to a hazard ratio of 0.92 (P = .55), which was not significant.

However, when the researchers added BMI into the multivariate analysis, they found that all of the differences were no longer significant, with a hazard ratio for IDFS for Black vs White women of 1.21 (P = .35), and a hazard ratio for Asian vs White women of 0.74 (P = .17).

Abdou said that the team will continue to analyze the RxPONDER data to determine whether there is an interaction between tumor biology, specifically altered gene groups, and race, and will explore the social determinants of health, based on patient geographic location, to examine issues around access to healthcare.

Finally, “we also plan to assess the likelihood of treatment completion and adherence by race and ethnicity beyond the first year.”

Reactions to the Findings

Commenting on the study, Lori J. Pierce, MD, radiation oncologist, professor, and vice provost for Academic and Faculty Affairs at the University of Michigan, Ann Arbor, highlighted that the study populations did not match the racial distribution of the overall US population in the 2021 census.

She emphasized that there are a number of clinician and patient barriers to the inclusion of patients of color into clinical trials.

These include limited physician communication with patients; inherent physician bias; a lack of knowledge regarding trial availability; a lack of diversity in the clinical workforce; trials not matching the type and stage of disease in clinical populations; social determinants of health; and distrust among patients.

Yet when patients are offered to participate in clinical trials, they agree at roughly similar rates, regardless of their race or ethnicity, she said.

Pierce added: “It’s very important to consider race, but we have to do so very thoughtfully so that we don’t perpetuate some of the concepts that we’re actually trying to disprove.

“Without a doubt, ancestry is so very important, but we also have to dig deeper to understand and address the hidden factors,” and the way in which social determinants of health “are contributing to disparities attributed to race.”

“I think this is our collective responsibility,” she said, “and I believe the onus is on us to do so.”

This study was funded by National Institutes of Health and National Cancer Institute grants; Susan G. Komen for the Cure Research Program; Hope Foundation for Cancer Research; Breast Cancer Research Foundation; and Genomic Health (now Exact Sciences Corporation).

Abdou reports relationships with AstraZeneca, Exact Sciences, MJH Holdings, MDEdge, and Clinical Care Options Oncology. Kaklamani reports relationships with Puma, AstraZeneca, Daiichi-Sankyo, Menarini, Gilead, Pfizer, Gilead, Genentech, Exact Sciences, Novartis, Seagen, and Eisai. Pierce reports an unpaid relationship with Exact Sciences.

San Antonio Breast Cancer Symposium (SABCS) 2022: Abstract GS1-01. Presented December 6, 2017.

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