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Associations of parity-related reproductive histories with ER± and HER2± receptor-specific breast cancer aetiology.

ABSTRACT: Associations of reproductive history with breast cancer risk differ by oestrogen receptor (ER±) status and possibly by the joint expression of ER and the human epidermal growth factor receptor-2 (ER±/HER2±). However, large sample sizes are needed to establish ER-specific risks by HER2± expression.We linked a cancer registry covering nearly 95% of the primary breast cancer diagnoses in Denmark with a research parity database to assess associations for parity, number of live births and age at first live birth (AFLB) with receptor-specific risk. Relative risks (RRs) for associations were estimated with Poisson regression models.With nearly 31 million women-years of follow-up, 45 786 Danish women aged 20-84 years developed invasive breast cancer during 1992-2011. ER± expression was available for the entire study period and HER2± after 2006. Of the breast cancers with known ER expression, 79% were ER+. Most breast cancers with known ER and HER2 were HER2- (90% of ER+ cancers and 65% of ER- cancers). RRs differed by ER± expression for all reproductive variables ( p -homogeneity < 0.001). Associations were stronger for ER+ than ER- cancers and for those diagnosed before age 50. Parity and early [not later] AFLB showed a protective association with ER+/HER2- and risk association with ER-/HER2- cancers.Associations of reproductive history with breast cancer risk varied among Danish women by ER± and ER±/HER2± expression and age-at-diagnosis, consistent with receptor-specific and age-related etiological heterogeneity. Further stratification by HER2 status demonstrated dual (or opposite) effects for ER+/HER2- and ER-/HER2- cancers.

SUBMITTER: Anderson WF

PROVIDER: S-EPMC5837631 | biostudies-other | 2017 Feb

REPOSITORIES: biostudies-other

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Associations of parity-related reproductive histories with ER± and HER2± receptor-specific breast cancer aetiology.

Anderson William F WF Pfeiffer Ruth M RM Wohlfahrt Jan J Ejlertsen Bent B Jensen Maj-Britt MB Kroman Niels N

International journal of epidemiology 20170201 1

<h4>Background</h4>Associations of reproductive history with breast cancer risk differ by oestrogen receptor (ER±) status and possibly by the joint expression of ER and the human epidermal growth factor receptor-2 (ER±/HER2±). However, large sample sizes are needed to establish ER-specific risks by HER2± expression.<h4>Methods</h4>We linked a cancer registry covering nearly 95% of the primary breast cancer diagnoses in Denmark with a research parity database to assess associations for parity, nu ...[more]

PMID: 27818374

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Project description:BackgroundTreatment strategies for various subtypes of breast cancer (BC) are different based on their distinct molecular characteristics. Therefore, it is very important to identify key differentially expressed genes (DEGs) between ER-positive/HER2-negative BC and ER-negative/HER2-negative BC.MethodsGene expression profiles of GSE22093 and GSE23988 were obtained from the Gene Expression Omnibus database. There were 74 ER-positive/HER2-negative BC tissues and 85 ER-negative/HER2-negative BC tissues in the two profile datasets. DEGs between ER-positive/HER2-negative tissues and ER-negative/HER2-negative BC tissues were identified by the GEO2R tool. The common DEGs among the two datasets were detected with Venn software online. Next, we made use of the Database for Annotation, Visualization and Integrated Discovery to analyze enriched Kyoto Encyclopedia of Gene and Genome (KEGG) pathways and gene ontology terms. Then, the protein-protein interactions (PPIs) of these DEGs were visualized by Cytoscape with the Search Tool for the Retrieval of Interacting Genes. Of the proteins in the PPI network, Molecular Complex Detection plug-in analysis identified nine core upregulated genes and one core downregulated gene. UALCAN and Gene Expression Profiling Interactive Analysis were applied to determine the expression of these 10 genes in BC. Furthermore, for the analysis of overall survival among those genes, the Kaplan-Meier method was implemented.ResultsNinety-three common DEGs (63 upregulated and 30 downregulated) were identified. KEGG pathway enrichment analysis showed that upregulated DEGs were particularly enriched in the progesterone-mediated oocyte maturation pathway. In addition, PGR might be a prognostic biomarker for ER-positive/HER2-negative BC. CCND1 is a poor prognostic biomarker for ER-positive/HER2-negative BC and ER-negative/HER2-negative BC. Moreover, TFF1, AGR2 and EGFR might be predictive biomarkers of node metastasis in ER-positive/HER2-negative BC and ER-negative/HER2-negative BC.ConclusionsCCND1, AGR2, PGR, TFF1 and EGFR are the key DEGs between ER-positive/HER2-negative BC and ER-negative/HER2-negative BC. Further studies are required to confirm the functions of the identified genes.

Dataset Information

Associations of parity-related reproductive histories with ER± and HER2± receptor-specific breast cancer aetiology.

Publications

Associations of parity-related reproductive histories with ER± and HER2± receptor-specific breast cancer aetiology.

Similar Datasets

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