Zhiyang Liu1,2, Zeyad Sahli2, Yongchun Wang2, Antonio C Wolff3, Leslie M Cope4, Christopher B Umbricht5. 1. Department of General Surgery, Qingdao Municipal Hospital (East), Qingdao, China. 2. Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA. 3. Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. 4. Department of Oncology Bioinformatics, The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA. 5. Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA. cumbrich@jhmi.edu.
Abstract
PURPOSE: Although age is a recognized independent prognostic risk factor, its relative importance among molecular subtypes of Breast cancer (BCA) is not well documented. The aim of this study was to evaluate the prognostic role of age at diagnosis among different immunohistochemical subtypes of BCA. METHODS: We conducted a retrospective study of women with invasive BCA undergoing surgery at the Johns Hopkins Hospital, excluding patients presenting with stage IV breast cancer. Patients were stratified into three age groups: ≤ 40, 41-60, and > 60 years, and multivariable analysis was performed using Cox regression. We also identified differentially expressed genes (DEG) between age groups among BCA subtypes in the public TCGA dataset. Finally, we identified key driver genes within the DEGs using a weighted gene co-expression network analysis. RESULTS: Luminal A breast cancer patients had significantly lower 5 year disease-free survival (DFS) and distant metastasis-free survival (DMFS) in the ≤ 40 year age group compared to the 41-60 year age group, while the other molecular subtypes showed no significant association of DFS or DMFS with age. Age was a stronger outcome predictor than tumor grade or proliferative index in Luminal A BCA patients, but not other subtypes. BCA TCGA gene expression data were divided into two groups (≤ 40 years, > 40 years). We identified 374 DEGs in the Luminal A BCA subset, which were enriched in seven pathways and two modules of co-expressed genes. No age group-specific DEGs were identified in non-Luminal A subtypes. CONCLUSIONS: Age at diagnosis may be an important prognostic factor in Luminal A BCA.
PURPOSE: Although age is a recognized independent prognostic risk factor, its relative importance among molecular subtypes of Breast cancer (BCA) is not well documented. The aim of this study was to evaluate the prognostic role of age at diagnosis among different immunohistochemical subtypes of BCA. METHODS: We conducted a retrospective study of women with invasive BCA undergoing surgery at the Johns Hopkins Hospital, excluding patientspresenting with stage IV breast cancer. Patients were stratified into three age groups: ≤ 40, 41-60, and > 60 years, and multivariable analysis was performed using Cox regression. We also identified differentially expressed genes (DEG) between age groups among BCA subtypes in the public TCGA dataset. Finally, we identified key driver genes within the DEGs using a weighted gene co-expression network analysis. RESULTS:Luminal A breast cancerpatients had significantly lower 5 year disease-free survival (DFS) and distant metastasis-free survival (DMFS) in the ≤ 40 year age group compared to the 41-60 year age group, while the other molecular subtypes showed no significant association of DFS or DMFS with age. Age was a stronger outcome predictor than tumor grade or proliferative index in Luminal A BCApatients, but not other subtypes. BCA TCGA gene expression data were divided into two groups (≤ 40 years, > 40 years). We identified 374 DEGs in the Luminal A BCA subset, which were enriched in seven pathways and two modules of co-expressed genes. No age group-specific DEGs were identified in non-Luminal A subtypes. CONCLUSIONS: Age at diagnosis may be an important prognostic factor in Luminal A BCA.
Entities:
Keywords:
Age; Breast cancer; Gene expression; Intrinsic subtype; Prognosis
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