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
Abstract
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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Article
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Published |
Creators/Authors: |
Creators | Email | Pitt Username | ORCID |
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Liao, S | | | | Hartmaier, RJ | rjh70@pitt.edu | RJH70 | orcid.org/0000-0001-7416-6036#sthash.wHE891bE.dpuf | McGuire, KP | | | | Puhalla, SL | slp55@pitt.edu | SLP55 | | Luthra, S | sol23@pitt.edu | SOL23 | | Chandran, UR | chandran@pitt.edu | CHANDRAN | | Ma, T | tim28@pitt.edu | TIM28 | | Bhargava, R | rob24@pitt.edu | ROB24 | | Modugno, F | ovarian@pitt.edu | OVARIAN | | Davidson, NE | ned23@pitt.edu | NED23 | | Benz, S | | | | Lee, AV | avl10@pitt.edu | AVL10 | | Tseng, GC | ctseng@pitt.edu | CTSENG | | Oesterreich, S | sto16@pitt.edu | STO16 | |
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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: |
School of Public Health > Biostatistics School of Public Health > Epidemiology 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: |
10 Jun 2023 11:55 |
URI: |
http://d-scholarship.pitt.edu/id/eprint/29215 |
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