Management of aromatase inhibitor-resistant disease with estrogen, selective estrogen receptor down-regulators, and other agents

Catherine Oakman, Libero Santarpia, Erica Moretti, Laura Biganzoli, Angelo Di Leo

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)24-33
Number of pages10
JournalCurrent Breast Cancer Reports
Volume3
Issue number1
DOIs
Publication statusPublished - Mar 2011

Keywords

  • Aromatase inhibitor resistance
  • Breast cancer
  • Estrogen, Long-term estrogen deprivation
  • Fulvestrant
  • Treatment resistance

ASJC Scopus subject areas

  • Oncology

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