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

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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.

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Disclosure

Angelo Di Leo has been a consultant for AstraZeneca and Pfizer and has received grants from AstraZeneca. The other authors report no potential conflicts of interest relevant to this article.

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Authors and Affiliations

  1. “Sandro Pitigliani” Medical Oncology Unit, Department of Oncology, Hospital of Prato, Istituto Toscano Tumori, Piazza Ospedale 2, Prato, 59100, Italy

    Catherine Oakman, Erica Moretti, Laura Biganzoli & Angelo Di Leo

  2. Translational Research Unit, Department of Oncology, Hospital of Prato, Istituto Toscano Tumori, Piazza Ospedale 2, Prato, 59100, Italy

    Libero Santarpia

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  1. Catherine Oakman
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Correspondence to Angelo Di Leo.

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Oakman, C., Santarpia, L., Moretti, E. et al. Management of Aromatase Inhibitor-Resistant Disease with Estrogen, Selective Estrogen Receptor Down-Regulators, and Other Agents. Curr Breast Cancer Rep 3, 24–33 (2011). https://doi.org/10.1007/s12609-010-0033-1

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