Synapse - Genomic landscape of breast cancer in elderly patients

Genomic landscape of breast cancer in elderly patients Journal Article

Authors:	Selenica, P.; Dopeso, H.; Repetto, M.; Basili, T.; Gazzo, A. M.; Schwartz, C. J.; Derakhshan, F.; Marra, A.; Ferrando, L.; Beets-Tan, R. G. H.; Wen, Y. H.; Ross, D. S.; Brogi, E.; Zhang, H.; Norton, L.; Chandarlapaty, S.; Razavi, P.; Mandelker, D.; Reis-Fiho, J. S.; Weigelt, B.; Pareja, F.
Article Title:	Genomic landscape of breast cancer in elderly patients
Abstract:	Breast cancer (BC) displays age-related histopathologic and transcriptomic heterogeneity. Whether BC in elderly patients differs genetically from that of younger individuals remains unclear. We re-analyzed sequencing data from 1918 BCs previously subjected to an FDA-cleared paired tumor-normal targeted sequencing assay across elderly (≥65 years), middle-aged (>45 and <65 years) and young (≥45 years) patients. BCs in elderly individuals exhibited fewer germline but were numerically enriched in somatic homologous recombination deficiency (HRD)/DNA damage response (DDR) genetic alterations. Primary ER+/HER2- BC in elderly patients showed shifts in the spectrum of actionable PI3K/AKT alterations, whereas metastatic cases were enriched in FAT1 and RB1 mutations and fewer ESR1 mutations, suggesting age-dependent therapeutic resistance mechanisms. Metastatic ER+/HER2- lobular BCs were enriched in actionable ERBB2 mutations. Resistance-associated alterations were more prevalent in metastatic vs primary BC in elderly patients. Our findings reveal distinct actionable genetic features in elderly patients, highlighting the importance of genomic profiling and treatment personalization in this population. © The Author(s) 2025.
Keywords:	immunohistochemistry; adult; human tissue; aged; unclassified drug; gene mutation; major clinical study; histopathology; breast cancer; brca1 protein; brca2 protein; transcriptomics; fluorescence in situ hybridization; atm protein; genomics; dna damage response; checkpoint kinase 2; brca1 associated ring domain protein 1; peptides and proteins; estrogen receptor alpha; pi3k/akt signaling; human; female; article; tumor mutational burden; partner and localizer of brca2; invasive lobular breast carcinoma; brct repeats of breast cancer type 1
Journal Title:	npj Breast Cancer
Volume:	11
ISSN:	2374-4677
Publisher:	Nature Publishing Group
Date Published:	2025-07-10
Start Page:	70
Language:	English
DOI:	10.1038/s41523-025-00781-4
PROVIDER:	scopus
PMCID:	PMC12246064
PUBMED:	40640183
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-105010415582&doi=10.1038%2fs41523-025-00781-4&partnerID=40&md5=64b02f602f1f3164cc20a3fe8c0a56d4
Notes:	The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PubMed record and PDF. Corresponding MSK authors are Britta Weigelt and Fresia Pareja -- Source: Scopus