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

ABSTRACT Breast cancer is the most commonly diagnosed cancer globally and the leading cause of cancer death in women, with ethnic disparities reported in cancer incidence, prognosis, diagnosis and therapeutic response. Although precision oncology holds the promise of revolutionising healthcare, it could exacerbate the racial disparities it seeks to eradicate unless rigorous efforts are made to address research biases. We evaluated the molecular and clinical effects of genetic ancestry in African and South Asian women using a combined cohort of 7,136 breast cancer patients available from four data sources – the 100,000 Genomes Project (UK), The Cancer Genome Atlas (US), the Breast Cancer Now Biobank (London, UK) and Genes South Asian: TP53 , BRCA1 , BRCA2 , p<0.05) as well as those implicated in breast cancer predisposition in the literature, such as CDH1 , CDK2A , ERCC3 , EPCAM , FANCA , FANCC, POLE and PMS2 . There is a higher propensity for BRCAness in the African population, with a lower rate in the South Asian population, serving as a potential prognostic indicator into the response to therapies such as PARP inhibitors. Our study confirms the under-representation of non-European ethnic minority groups within research studies, clinical applications and biobanks, with none of the resources able to recapitulate the ethnic diversity of their representative geographical locations (UK, London and US). Finally, our findings advocate for the implementation of ancestry-specific germline mutation breast cancer screening windows and germline screening panels. This study harnesses multimodal data to improve our understanding of ancestry-associated differences in breast cancer and highlight opportunities to advance health equity in breast cancer thus taking one step closer to achieving the promise of equitable precision oncology.