The molecular landscape of premenopausal breast cancer.

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.

• Authors: 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
• Journal: Breast cancer research : BCR (Breast Cancer Res) Vol. 17 Pg. 104 (Aug 07 2015) ISSN: 1465-542X [Electronic] England
• PMID: 26251034 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor

Topics

• Biomarkers, Tumor
• Breast Neoplasms (epidemiology, genetics)
• Cluster Analysis
• Computational Biology
• DNA Copy Number Variations
• DNA Methylation
• Databases, Genetic
• Female
• Gene Expression Profiling
• Gene Expression Regulation
• Humans
• Mutation
• Outcome Assessment, Health Care
• Postmenopause
• Premenopause
• Prognosis
• Proteomics
• Reproducibility of Results
• Signal Transduction