Genomic characterisation of hormone receptor-positive breast cancer arising in very young women

BACKGROUND: Very young premenopausal women diagnosed with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+HER2-) early breast cancer (EBC) have higher rates of recurrence and death for reasons that remain largely unexplained. PATIENTS AND METHODS: Genomic sequencing was applied to HR+HER2- tumours from patients enrolled in the Suppression of Ovarian Function Trial (SOFT) to determine genomic drivers that are enriched in young premenopausal women. Genomic alterations were characterised using next-generation sequencing from a subset of 1276 patients (deep targeted sequencing, n = 1258; whole-exome sequencing in a young-age, case-control subsample, n = 82). We defined copy number (CN) subgroups and assessed for features suggestive of homologous recombination deficiency (HRD). Genomic alteration frequencies were compared between young premenopausal women (