The molecular landscape of premenopausal breast cancer

Serena Liao, Ryan J. Hartmaier, Kandace P. McGuire, Shannon L. Puhalla, Soumya Luthra, Uma R. Chandran, Tianzhou Ma, Rohit Bhargava, Francesmary Modugno, Nancy E. Davidson, Steve Benz, Adrian V. Lee, George C. Tseng, Steffi Oesterreich

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number104
JournalBreast Cancer Research
Volume17
Issue number1
DOIs
Publication statusPublished - Aug 7 2015
Externally publishedYes

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Liao, S., Hartmaier, R. J., McGuire, K. P., Puhalla, S. L., Luthra, S., Chandran, U. R., ... Oesterreich, S. (2015). The molecular landscape of premenopausal breast cancer. Breast Cancer Research, 17(1), [104]. https://doi.org/10.1186/s13058-015-0618-8