Plenary Lecture to Untangle Drivers of Racial Disparities in Breast Cancer

The first Plenary Lecture of the 2024 San Antonio Breast Cancer Symposium® will offer a detailed look at the knot of social and biological drivers that underlie racial disparities in breast cancer outcomes.

Melissa Davis, PhD, Georgia Research Alliance Distinguished Investigator at the Morehouse School of Medicine Institute of Translational Genomic Medicine, will explore The Grand Challenge of Unraveling Social vs. Biological Drivers of Racial Disparities in Cancer Outcomes on Thursday, December 12, from 8:30 to 9 a.m. CT in Hall 1.

Disparities in health care outcomes are driven by multiple interrelated threads, Dr. Davis said. Initially, studies that interrogated population-based disparities used boundaries related to race as a proxy for shared group attributes. But in the United States, racial boundaries have often been used to marginalize populations in systematic ways by linking ancestry and skin color with socioeconomic strata.

At the same time, these marginalized groups have not been included in genomic studies, largely due to sampling bias.

“The genomic studies that predate work that is happening now primarily depended on relying on participation of patients/people walking into academic institutions,” she explained. “Large teaching hospitals, large cancer centers, and the communities those clinics serve don’t typically reach into under-supported marginalized areas. The only investigators faithfully studying marginalized groups were mostly concerned with social determinants of health. We have a knowledge gap.”

Most of the genomic data that has been used to define understanding of cancer pathogenesis, disease progression, and treatment is derived from individuals of European ancestry, Dr. Davis noted. Less than 10% of the data represent more than 80% of the global population.

In breast cancer, for example, genomics data from individuals largely of European descent were used to define molecular subtypes of breast cancer, yet are primarily defined in clinic with only three histology markers contributing to hormone receptor status. These are still the primary biomarkers for diagnosis and treatment decisions. Current technology is identifying thousands of genes that underlie breast cancer with multiple categories and biomarkers beyond hormone receptors.

“If we use additional biomarkers, we can see a bias in the presence of certain subtypes of breast cancer that coincide with these race populations,” Dr. Davis said. “And if we step out of the United States, where our social construct of race isn’t necessarily the demarcating factor, we saw emerging in Sub-Saharan West Africa the most aggressive subtypes of these tumors. There is more to it than just social deprivation and marginalized society here in the United States. The underlying biology could potentially be something that is shared in a genetic lineage all the way back to Sub-Saharan Africa.”

This is not to say environment is not a major factor in outcome disparities. African and African American populations share genetic background, but comparing these populations reveals gene expressions unrelated to germline differences.

“These gene expression patterns were related to the comorbidities in the African American population: obesity, diabetes, cardiac dysfunction, insulin resistance,” Dr. Davis said. “These are the patients coming into clinic who have been impacted by their marginalized living conditions. And these patients are systematically not eligible for clinical trials because of obesity, cardiovascular disease, diabetes. We have no idea what cancer drugs are doing in these populations because they have never been studied.”

Unraveling the social and biologic drivers of cancer is in the early stages but new targets are already emerging. It is becoming clear that immunotherapy, for example, can benefit populations differently due to differences in tumor microenvironment.

“This is a revelation in progress, a traveling tsunami,” Dr. Davis said. “Let’s move forward to learn more and do more.”