Treatment disparity in mBC between women of color and white women

Last Updated on March 1, 2025 by Joseph Gut – thasso

February 20, 2025 – 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, women of color (“black patients”) were significantly less likely to receive targeted PI3K inhibitor therapy, highlighting treatment disparities. PIK3CA has been found to be oncogenic and is implicated in cervical cancers. Also,PIK3CA mutations are present in over one-third of breast cancers, with enrichment in the luminal and in human epidermal growth factor receptor 2-positive subtypes (HER2 +). Three hotspot mutation positions (GLU542, GLU545, and HIS1047) are well known in this oncogene.

The recent incorporation of circulating tumor DNA (ctDNA) into standard criniacalpractice 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 2015 and December 2023.

Analysis included 1327 women with mBC (mean [SD] age, 58.0 [12.8] years; 140 Black women and 1057 White women) 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.

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.

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 implementation of science interventions,” wrote the authors of the study.

Here, we can only hope that the envisaged science interventions also will active for all the women of color in Africa too. Breast cancer is the commonest cause of global cancer-related deaths in women and a public health burden Sub-Saharan Africa (SSA) as well summarized in overwiews by the IARC and the NIH. Although the disease incidence in SSA seems lower, mortality rates are disproportionately high in comparison to high-income countries. The global disease burden is growing, with SSA reporting the majority of cases; however, the dearth of information results in insufficient data which is barely representative of the actual disease burden in this population. Future incidence predictions assign the subregion with a majority of the cases and associated deaths. Breast cancer presents with racial and ethnic variations, and available evidence suggests geographical diversity and persistent risk factors that have barely been explored in SSA. Breast cancer is a complex genetic disease, but the genetic risk factors in the extant African population, which is the most genetically diverse population, is scant and of low quality. This review focuses on the burden, prevalence, detection, treatment, survival, biology, as well as risk factors, and reinforces the need for breast cancer-associated risk factor investigation and population-specific studies in SSA; At the end od the day, it is hoped that sophisticated genetic analyses like the PIK3CA variations described above may become implemented in SSA and help save patients lives.

See this sequence as a reminder of what affected women may go trough: