TY - JOUR
T1 - The molecular landscape of premenopausal breast cancer
AU - Liao, Serena
AU - Hartmaier, Ryan J.
AU - McGuire, Kandace P.
AU - Puhalla, Shannon L.
AU - Luthra, Soumya
AU - Chandran, Uma R.
AU - Ma, Tianzhou
AU - Bhargava, Rohit
AU - Modugno, Francesmary
AU - Davidson, Nancy E.
AU - Benz, Steve
AU - Lee, Adrian V.
AU - Tseng, George C.
AU - Oesterreich, Steffi
N1 - Funding Information:
METABRIC data were accessed through Synapse (synapse.sagebase.org). RJH was supported by a DOD Postdoctoral Fellowship (W81XWH-11-1-0582), and SO, NED, and AVL are supported by BCRF. This project used the UPCI Cancer Bioinformatics Core that is supported in part by award P30CA047904. This work was also in part supported by the UPMC Enterprise Analytics program and the use of the Oracle Health Sciences Translational Research Center, through Glimmer of Hope (KM), and through research funds from UPMC. The authors would like to thank Drs Xinghua Lu and Chunhui Cai for providing R code for implementation of BCI.
Publisher Copyright:
© 2015 Liao et al.
PY - 2015/8/7
Y1 - 2015/8/7
N2 - 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.
AB - 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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U2 - 10.1186/s13058-015-0618-8
DO - 10.1186/s13058-015-0618-8
M3 - Article
C2 - 26251034
AN - SCOPUS:84938591277
SN - 1465-5411
VL - 17
JO - Breast Cancer Research
JF - Breast Cancer Research
IS - 1
M1 - 104
ER -