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01.12.2008 | Preclinical Study

Molecular signatures of neoadjuvant endocrine therapy for breast cancer: characteristics of response or intrinsic resistance

verfasst von: Djuana M. E. Harvell, Nicole S. Spoelstra, Meenakshi Singh, James L. McManaman, Christina Finlayson, Tzu Phang, Susan Trapp, Lawrence Hunter, Wendy W. Dye, Virginia F. Borges, Anthony Elias, Kathryn B. Horwitz, Jennifer K. Richer

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 3/2008

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Abstract

Approximately 30% of patients with estrogen receptor (ER) positive breast cancers exhibit de novo or intrinsic resistance to endocrine therapies. The purpose of this study was to define genes that distinguish ER+ resistant from ER+ responsive tumors, prior to the start of hormone therapies. Previously untreated post-menopausal patients with ER+ breast cancers were treated for 4 months in a neoadjuvant setting with the aromatase inhibitor exemestane alone, or in combination with the antiestrogen tamoxifen. Matched pre- and post-treatment tumor samples from the same patient, were analyzed by gene expression profiling and were correlated with response to treatment. Genes associated with tumor shrinkage achieved by estrogen blockade therapy were identified, as were genes associated with resistance to treatment. Prediction Analysis of Microarrays (PAM) identified 50 genes that can predict response or intrinsic resistance to neoadjuvant endocrine therapy of ER+ tumors, 8 of which have been previously implicated as useful biomarkers in breast cancer. In summary, we identify genes associated with response to endocrine therapy that may distinguish ER+, hormone responsive breast cancers, from ER+ tumors that exhibit intrinsic or de novo resistance. We suggest that the estrogen signaling pathway is aberrant in ER+ tumors with intrinsic resistance. Lastly, the studies show upregulation of a “lipogenic pathway” in non-responsive ER+ tumors that may serve as a marker of intrinsic resistance. This pathway may represent an alternative target for therapeutic intervention.

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Titel: Molecular signatures of neoadjuvant endocrine therapy for breast cancer: characteristics of response or intrinsic resistance
verfasst von: Djuana M. E. Harvell
Nicole S. Spoelstra
Meenakshi Singh
James L. McManaman
Christina Finlayson
Tzu Phang
Susan Trapp
Lawrence Hunter
Wendy W. Dye
Virginia F. Borges
Anthony Elias
Kathryn B. Horwitz
Jennifer K. Richer
Publikationsdatum: 01.12.2008
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 3/2008
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-008-9897-4

Springer Medizin

Molecular signatures of neoadjuvant endocrine therapy for breast cancer: characteristics of response or intrinsic resistance

Abstract

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Springer Medizin

Abstract

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