PO-310 Genomic features of premenopausal breast cancers in latin american women: the PRECAMA study

Abstract

Introduction In Latin America (LA), there is a high incidence rate of breast cancer (BC) in premenopausal women, and the genomic features of these BC remain unknown. Here, we have characterised the molecular features of BC in young LA women within the framework of the PRECAMA study, a multicenter population-based case-control study on breast cancer in premenopausal women. Material and methods Pathological tumour tissues were collected from incident cases from four LA countries. Immunohistochemistry (IHC) was performed centrally for ER, PR, HER2, Ki67, EGFR, CK5/6 and p53 protein markers. Targeted deep sequencing was done on genomic DNA extracted from formalin-fixed paraffin-embedded (FFPE) tumour tissues and their paired blood samples to screen for somatic mutations in eight genes frequently mutated in BC. A subset of samples was analysed by exome sequencing to identify somatic mutational signatures. Results and discussions The majority of cases were positive for ER or PR (168/233; 72%) and 21% of cases were triple negative (TN), mainly of basal type. Most tumours were positive for Ki67 (189/233; 81%). In 126 sequenced cases, TP53 and PIK3CA were the most frequently mutated genes (32.5% and 21.4%, respectively), followed by AKT1 (9.5%). TP53 mutations were more frequent in HER2-enriched and TN IHC subtypes, while PIK3CA/AKT1 mutations were more frequent in ER-positive tumours, as expected. Interestingly, a higher proportion of G:C>T:A mutation type was observed in TP53 gene in PRECAMA cases compared to TCGA and METABRIC breast cancer series (27% vs 14%). Exome-wide mutational patterns in 10 TN cases revealed alterations in signalling transduction pathways and major contributions of mutational signatures caused by altered DNA repair pathways. Conclusion This pilot study on PRECAMA tumours gives a preview of the molecular features of premenopausal BC in LA. Although the overall mutation burden was as expected from data in other populations, mutational patterns observed in TP53 and exome-wide suggested possible differences in mutagenic processes giving rise to these tumours compared to other populations. Further omics analyses of a larger number of cases in the near future will allow investigating relationships between these molecular features and risk factors.