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The molecular landscape of premenopausal breast cancer

Liao, S and Hartmaier, RJ and McGuire, KP and Puhalla, SL and Luthra, S and Chandran, UR and Ma, T and Bhargava, R and Modugno, F and Davidson, NE and Benz, S and Lee, AV and Tseng, GC and Oesterreich, S (2015) The molecular landscape of premenopausal breast cancer. Breast Cancer Research, 17 (1). ISSN 1465-5411

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Introduction: Breast cancer in premenopausal women (preM) is frequently associated with worse prognosis compared to that in postmenopausal women (postM), and there is evidence that preM estrogen receptor-positive (ER+) tumors may respond poorly to endocrine therapy. There is, however, a paucity of studies characterizing molecular alterations in premenopausal tumors, a potential avenue for personalizing therapy for this group of women. Methods: Using TCGA and METABRIC databases, we analyzed gene expression, copy number, methylation, somatic mutation, and reverse-phase protein array data in breast cancers from >2,500 preM and postM women. Results: PreM tumors showed unique gene expression compared to postM tumors, however, this difference was limited to ER+ tumors. ER+ preM tumors showed unique DNA methylation, copy number and somatic mutations. Integrative pathway analysis revealed that preM tumors had elevated integrin/laminin and EGFR signaling, with enrichment for upstream TGFβ-regulation. Finally, preM tumors showed three different gene expression clusters with significantly different outcomes. Conclusion: Together these data suggest that ER+ preM tumors have distinct molecular characteristics compared to ER+ postM tumors, particularly with respect to integrin/laminin and EGFR signaling, which may represent therapeutic targets in this subgroup of breast cancers.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Liao, S
McGuire, KP
Puhalla, SLslp55@pitt.eduSLP55
Luthra, Ssol23@pitt.eduSOL23
Chandran, URchandran@pitt.eduCHANDRAN
Ma, Ttim28@pitt.eduTIM28
Bhargava, Rrob24@pitt.eduROB24
Modugno, Fovarian@pitt.eduOVARIAN
Davidson, NEned23@pitt.eduNED23
Benz, S
Lee, AVavl10@pitt.eduAVL10
Tseng, GC
Oesterreich, Ssto16@pitt.eduSTO16
Centers: Other Centers, Institutes, Offices, or Units > Magee-Women's Research Institute
Other Centers, Institutes, Offices, or Units > Pittsburgh Cancer Institute
Date: 7 August 2015
Date Type: Publication
Journal or Publication Title: Breast Cancer Research
Volume: 17
Number: 1
DOI or Unique Handle: 10.1186/s13058-015-0618-8
Schools and Programs: Graduate School of Public Health > Biostatistics
Graduate School of Public Health > Epidemiology
Graduate School of Public Health > Human Genetics
School of Medicine > Biomedical Informatics
School of Medicine > Computational Biology
School of Medicine > Obstetrics, Gynecology, and Reproductive Sciences
School of Medicine > Pathology
School of Medicine > Pharmacology and Chemical Biology
School of Medicine > Surgery
Refereed: Yes
ISSN: 1465-5411
Date Deposited: 17 Aug 2016 13:51
Last Modified: 30 Mar 2021 13:56


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