The clinical and molecular landscape of breast cancer in women of African and South Asian ancestry

Abstract

Our study evaluates the molecular and clinical effects of genetic ancestry in African and South Asian women compared to European using a combined cohort of 7,253 breast cancer patients available from four data sources: the 100,000 Genomes Project (UK), The Cancer Genome Atlas (US), the Breast Cancer Now Biobank (UK) and Genes & Health (UK). We find that non-European breast cancer patients present significantly earlier and die at a younger age. The African ancestry group has an increased prevalence of higher grade and hormone receptor negative disease. The South Asian group shows tendency towards lower stage at diagnosis and lower tumour mutational burden. We observe significant differences and similarities in the somatic mutational landscape. We identify differences in germline mutation rates in genes used in genetic testing and others implicated in breast cancer predisposition. Potential therapeutic targets are differentially mutated. We report a higher propensity for homologous recombination deficiency serving as a potential therapy response indicator. Although precision oncology holds the promise of revolutionising healthcare, it could exacerbate the disparities it seeks to eradicate unless research biases are addressed. We harness multimodal data to improve our understanding of ancestry-associated differences in breast cancer and highlight opportunities to advance health equity.