The molecular landscape of premenopausal breast cancer. Issue 1 (December 2015)

• Record Type: Journal Article
• Authors: Liao, Serena; Hartmaier, Ryan; McGuire, Kandace; Puhalla, Shannon; Luthra, Soumya; Chandran, Uma; Ma, Tianzhou; Bhargava, Rohit; Modugno, Francesmary; Davidson, Nancy; Benz, Steve; Lee, Adrian; Tseng, George; Oesterreich, Steffi
• Is Part Of: Breast cancer research. Volume 17:Issue 1(2015)
• Page Start: 1
• Page End: 13
• Publication Date: 2015-12
• Subjects: Breast -- Cancer -- Periodicals; 616.99449
• DOI: 10.1186/s13058-015-0618-8
• Languages: English
• ISSNs: 1465-542X

Abstract

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.