A recent study published in JAMA Network Open explores disparities in outcomes and treatment among Black and White patients with metastatic breast cancer (mBC). The research, led by Dr. Emily L. Podany and her team at Washington University in St. Louis, investigated whether Black patients with mBC have distinct genomic profiles compared to White patients and whether these differences contribute to inequities in targeted treatment.
The study analyzed data from adult patients diagnosed with mBC who underwent genomic profiling at academic institutions in the U.S. between January 1, 2015, and December 31, 2023. The cohort included 1,327 women with a mean age of 58, consisting of 140 Black patients and 1,057 White patients. The primary focus was to compare the variations in circulating tumor DNA (ctDNA) profiles and the use of targeted therapies, such as phosphoinositide 3-kinase (PI3K) inhibitors, mammalian target of rapamycin (mTOR) inhibitors, and cyclin-dependent kinase 4/6 (CDK4/6) inhibitors between the two racial groups.
The study found significant differences in the genetic alterations between Black and White patients. In multivariate analysis, Black patients exhibited a much higher rate of specific genetic variants. These included GATA3 single-nucleotide variants, with an odds ratio (OR) of 2.31, and CCND2 copy number variants, with an OR of 4.63. These results were corroborated by a population-based evidence cohort that included 27,224 patients, confirming the higher frequency of these alterations in Black patients.
When examining treatment disparities, the study revealed that Black patients were less likely to be prescribed PI3K inhibitors, even when they had PIK3CA single-nucleotide variants, compared to their White counterparts. The rates of PI3K inhibitor prescriptions were 5.9% for Black patients versus 28.8% for White patients. Additionally, Black patients were less likely to be enrolled in clinical trials, further highlighting systemic inequities in access to advanced treatment options. However, there were no significant differences in the use of CDK4/6 or mTOR inhibitors, treatments that do not require specific genetic alterations.
The study also found that Black patients experienced shorter overall survival after ctDNA testing compared to White patients, suggesting that the disparities in treatment access and genomic alterations might contribute to poorer outcomes in this population.
Despite these significant findings, the authors acknowledged several limitations in the study. It was a retrospective cohort study, meaning that it relied on existing data, which may have been influenced by confounding factors such as comorbidities, lifestyle choices, and social determinants of health. The study’s cohort was also limited to patients who had access to ctDNA testing at large, urban academic centers and who chose to participate in the study, which may have introduced selection bias. Additionally, the study noted that the small number of patients enrolled in clinical trials made it difficult to draw definitive conclusions about the impact of these trials on treatment outcomes. Finally, the reliance on self-reported race in the study may have led to inaccuracies, as genetic ancestry could provide a more precise understanding of the variations observed in the patients’ tumors.
The researchers concluded that despite having similar rates of PIK3CA genetic alterations, Black patients with metastatic breast cancer face distinct somatic differences, shorter survival, and disparities in the use of targeted treatments like PI3K inhibitors. These findings highlight the persistent gap in outcomes between Black and White patients and emphasize the need for more equitable approaches in both research and clinical practice. The authors advocate for future research and interventions that consider these disparities to improve outcomes for Black patients with mBC.
