Genomic landscape of breast cancer in elderly patients.

IF 7.6 2区医学 Q1 ONCOLOGY

NPJ Breast Cancer Pub Date : 2025-07-10 DOI:10.1038/s41523-025-00781-4

Pier Selenica, Higinio Dopeso, Matteo Repetto, Thais Basili, Andrea M Gazzo, Christopher J Schwartz, Fatemeh Derakhshan, Antonio Marra, Lorenzo Ferrando, Regina G H Beets-Tan, Y H Wen, Dara S Ross, Edi Brogi, Hong Zhang, Larry Norton, Sarat Chandarlapaty, Pedram Razavi, Diana Mandelker, Jorge S Reis-Fiho, Britta Weigelt, Fresia Pareja

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引用次数: 0

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.

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老年乳腺癌患者的基因组图谱。

乳腺癌（BC）表现出与年龄相关的组织病理学和转录组异质性。老年患者的BC在基因上是否与年轻人不同尚不清楚。我们重新分析了1918例bc的测序数据，这些bc先前接受了fda批准的配对肿瘤正常靶向测序测定，包括老年人（≥65岁）、中年人（45岁以上和65岁以下）

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

NPJ Breast Cancer Medicine-Pharmacology (medical)

CiteScore

10.10

自引率

1.70%

发文量

122

审稿时长

9 weeks

期刊介绍： npj Breast Cancer publishes original research articles, reviews, brief correspondence, meeting reports, editorial summaries and hypothesis generating observations which could be unexplained or preliminary findings from experiments, novel ideas, or the framing of new questions that need to be solved. Featured topics of the journal include imaging, immunotherapy, molecular classification of disease, mechanism-based therapies largely targeting signal transduction pathways, carcinogenesis including hereditary susceptibility and molecular epidemiology, survivorship issues including long-term toxicities of treatment and secondary neoplasm occurrence, the biophysics of cancer, mechanisms of metastasis and their perturbation, and studies of the tumor microenvironment.