Racial Gaps Persist in Cancer Genomics and Treatment

TOPLINE:

Black patients with metastatic breast cancer (mBC) showed distinct genomic profiles, including higher rates of specific genetic variants, compared with White patients. Despite equal incidence of PIK3CA alterations, Black patients were significantly less likely to receive targeted PI3K inhibitor therapy, highlighting treatment disparities.

METHODOLOGY:

• The recent incorporation of circulating tumor DNA (ctDNA) into standard practice has created an opportunity to evaluate genomic differences between Black and White patients with mBC.
• Researchers conducted a retrospective, population-based cohort study of adult patients with mBC who underwent genomic profiling at academic institutions in the United States between January 1, 2015, and December 31, 2023.
• Analysis included 1327 women with mBC (mean [SD] age, 58.0 [12.8] years; 140 Black and 1057 White) from Washington University in St. Louis, St. Louis, Northwestern University, Evanston, Illinois, and Massachusetts General Hospital, Boston.
• Investigators examined circulating tumor DNA profiles and the use of phosphoinositide 3-kinase, mammalian target of rapamycin, and cyclin-dependent kinase 4/6 (CDK4/6) inhibitors of Black and White patients.
• Data collection encompassed metastatic disease sites, pathologic data, patient-reported race and ethnicity, prior treatments, and progression-free survival for each treatment line and overall survival from the date of initial ctDNA collection.

TAKEAWAY:

• Black patients showed significantly higher rates of GATA3 single-nucleotide variants (odds ratio [OR], 2.31; 95% CI, 1.17-4.54; P = .02) and CCND2 copy number variants (OR, 4.63; 95% CI, 1.79-11.97; P = .002) on multivariate analysis.
• Among patients with PIK3CA single-nucleotide variants, Black patients were significantly less likely to receive PI3K inhibitors compared with White patients (5.9% vs 28.8%; P = .04), while no difference was observed in use of CDK4/6 and mammalian target of rapamycin inhibitors.
• Genomic differences between Black and White patients were validated in a population-based evidence cohort of 27,224 patients.
• Black patients demonstrated shorter overall survival from the time of ctDNA testing than White patients.

IN PRACTICE:

“Future preclinical studies should assess the impact of these observed somatic differences on the biology of mBC, and clinical studies should further evaluate how HbA1c and social determinants of health may impact clinical trial enrollment and OS…The disparity in use of targeted treatments for patients with PIK3CA alterations shows that clinical inequities exist alongside genomic differences, which must be a focus for future implementation of science interventions,” wrote the authors of the study.

SOURCE:

The study was led by Emily Podany, MD, Washington University in St. Louis. It was published online in JAMA Network Open.

LIMITATIONS:

As a retrospective cohort study, researchers noted that comorbidities, lifestyle factors, and social determinants of health were not fully accounted for in the analyses. Selection bias may exist as patients had access to ctDNA testing at large, urban academic centers and opted to receive it. The small number of patients enrolled in clinical trials limits the ability to draw strong conclusions from these data. Additionally, self-reported race may not accurately reflect genetic ancestry, which could provide a more precise understanding of the observed somatic tumor variations.

DISCLOSURES:

Lorenzo Gerratana, MD, disclosed receiving personal fees from AstraZeneca, Daiichi Sankyo, Eli Lilly and Company, GlaxoSmithKline, Incyte, Novartis, Pfizer, Merck Sharp & Dohme, Menarini Stemline, and AbbVie outside the submitted work. Arielle Medford, MD, disclosed receiving personal fees from AstraZeneca, Edgewood Oncology, Guardant Health, Illumina, Myriad Genetics, Natera, and Science for America outside the submitted work. Katherine Clifton, MD, reported serving on the Novartis Advisory Board. Adrian Bubie, MS, reported being employed by Guardant Health, Inc. Fabio Puglisi, MD, PhD, disclosed receiving grants from AstraZeneca, Eisai Pharmaceuticals, and Roche, as well as personal fees from multiple pharmaceutical companies. Aditya Bardia, MD, disclosed receiving grants and personal fees from several pharmaceutical companies including Pfizer, Novartis, Genentech, Merck, Menarini, Gilead, Sanofi, Daiichi Pharma/AstraZeneca, and Eli Lilly and Company. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.