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

Addressing existing racial disparity in breast cancer is crucial to ensure equitable benefit across diverse communities. We evaluate the molecular and clinical effects of genetic ancestry in African and South Asian women compared to European using a combined cohort of 7136 breast cancer patients. We find that non-European patients present significantly earlier and die at a younger age. The African 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 tumour mutational burden. We observe differences and similarities in the somatic mutational landscape, and differences in germline mutation rates relevant to genetic testing and breast cancer predisposition. Potential therapeutic candidates are identified, with a higher propensity for homologous recombination deficiency serving as a therapy response indicator. We harness breast cancer multimodal data to improve understanding of ancestry-associated differences and highlight opportunities to advance health equity.