Association of early menarche with breast tumor molecular features and recurrence

作者：Alexandra R. Harris, Tengteng Wang, Yujing J. Heng, Gabrielle M. Baker, Phuong Anh Le, Jun Wang, Christine B. Ambrosone, Adam Brufsky, Fergus J. Couch, Francesmary Modugno, Christopher G. Scott, Celine M. Vachon, Susan E. Hankinson, Bernard Rosner, Rulla M. Tamimi, Cheng Peng, A. Heather Eliassen · 发表于：Breast Cancer Research · 年份：2024 · DOI：10.1186/s13058-024-01839-0 · 被引用次数：21 · 研究领域：Breast Lesions and Carcinomas、Breast Cancer Treatment Studies、Hypothalamic control of reproductive hormones

Abstract Background Early menarche is an established risk factor for breast cancer but its molecular contribution to tumor biology and prognosis remains unclear. Methods We profiled transcriptome-wide gene expression in breast tumors (N = 846) and tumor-adjacent normal tissues (N = 666) from women in the Nurses’ Health Studies (NHS) to investigate whether early menarche (age < 12) is associated with tumor molecular and prognostic features in women with breast cancer. Multivariable linear regression and pathway analyses using competitive gene set enrichment analysis were conducted in both tumor and adjacent-normal tissue and externally validated in TCGA (N = 116). Subgroup analyses stratified on ER-status based on the tumor were also performed. PAM50 signatures were used for tumor molecular subtyping and to generate proliferation and risk of recurrence scores. We created a gene expression score using LASSO regression to capture early menarche based on 28 genes from FDR-significant pathways in breast tumor tissue in NHS and tested its association with 10-year disease-free survival in both NHS (N = 836) and METABRIC (N = 952). Results Early menarche was significantly associated with 369 individual genes in adjacent-normal tissues implicated in extracellular matrix, cell adhesion, and invasion (FDR ≤ 0.1). Early menarche was associated with upregulation of cancer hallmark pathways (18 significant pathways in tumor, 23 in tumor-adjacent normal, FDR ≤ 0.1) related to proliferati...