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- Title
The molecular landscape of premenopausal breast cancer.
- Authors
Liao, Serena; Hartmaier, Ryan J; McGuire, Kandace P; Puhalla, Shannon L; Luthra, Soumya; Chandran, Uma R; Ma, Tianzhou; Bhargava, Rohit; Modugno, Francesmary; Davidson, Nancy E; Benz, Steve; Lee, Adrian V; Tseng, George C; Oesterreich, Steffi
- Abstract
<bold>Introduction: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusion: </bold>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.
- Publication
Breast Cancer Research, 2015, Vol 17, Issue 1, p104
- ISSN
1465-5411
- Publication type
journal article
- DOI
10.1186/s13058-015-0618-8