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Management of Aromatase Inhibitor-Resistant Disease with Estrogen, Selective Estrogen Receptor Down-Regulators, and Other Agents

Management of Aromatase Inhibitor-Resistant Disease with Estrogen, Selective Estrogen Receptor... With increased use of aromatase inhibitors (AIs) in the adjuvant and first-line metastatic settings for postmenopausal women with estrogen receptor (ER)-positive breast cancer, systemic relapse or progressive metastatic disease on AIs is an increasingly encountered clinical scenario. Overcoming resistance is a priority. Patients with AI-resistant disease represent a heterogeneous population, with diverse mechanisms of resistance dictating varied sensitivity to subsequent treatment. Cells with persistent dependence on ER signaling may be inhibited by fulvestrant, in which case dose-dependent ER downregulation and activity favor high-dose, loading schedule fulvestrant. In direct contrast, cells with long-term estrogen deprivation with adaptive estrogen hypersensitivity may be inhibited by exposure to estrogen. Cell survival by alternate growth signaling pathways may be inhibited by targeted agents. Currently missing, however, are predictive biomarkers to identify underlying resistance mechanisms and guide effective post-AI therapy for individual patients. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Current Breast Cancer Reports Springer Journals

Management of Aromatase Inhibitor-Resistant Disease with Estrogen, Selective Estrogen Receptor Down-Regulators, and Other Agents

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References (54)

Publisher
Springer Journals
Copyright
Copyright © 2011 by Springer Science+Business Media, LLC
Subject
Medicine & Public Health; Surgical Oncology; Internal Medicine; Oncology
ISSN
1943-4588
eISSN
1943-4596
DOI
10.1007/s12609-010-0033-1
Publisher site
See Article on Publisher Site

Abstract

With increased use of aromatase inhibitors (AIs) in the adjuvant and first-line metastatic settings for postmenopausal women with estrogen receptor (ER)-positive breast cancer, systemic relapse or progressive metastatic disease on AIs is an increasingly encountered clinical scenario. Overcoming resistance is a priority. Patients with AI-resistant disease represent a heterogeneous population, with diverse mechanisms of resistance dictating varied sensitivity to subsequent treatment. Cells with persistent dependence on ER signaling may be inhibited by fulvestrant, in which case dose-dependent ER downregulation and activity favor high-dose, loading schedule fulvestrant. In direct contrast, cells with long-term estrogen deprivation with adaptive estrogen hypersensitivity may be inhibited by exposure to estrogen. Cell survival by alternate growth signaling pathways may be inhibited by targeted agents. Currently missing, however, are predictive biomarkers to identify underlying resistance mechanisms and guide effective post-AI therapy for individual patients.

Journal

Current Breast Cancer Reports – Springer Journals

Published: Jan 13, 2011

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