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Review

mTOR inhibitors: changing landscape of endocrine-resistant breast cancer

    Saranya Chumsri

    Department of Medicine, University of Maryland, Greenebaum Cancer Center, Baltimore, MD, USA

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    ,
    Gauri Sabnis

    Department of Pharmacology & Experimental Therapeutics, University of Maryland, Greenebaum Cancer Center, Baltimore, MD, USA

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    ,
    Katherine Tkaczuk

    Department of Medicine, University of Maryland, Greenebaum Cancer Center, Baltimore, MD, USA

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    &
    Angela Brodie

    Department of Pharmacology & Experimental Therapeutics, University of Maryland, Greenebaum Cancer Center, Baltimore, MD, USA

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    Published Online:24 Feb 2014https://doi.org/10.2217/fon.13.178

    Abstract

    ABSTRACT: 

    Most breast cancer (BC) patients have tumors that express hormone receptors (HRs). Although endocrine therapy, such as aromatase inhibitors, is very effective, most patients with metastatic HR-positive (HR+) BC become resistant to endocrine therapy at some point in their treatment and subsequently require chemotherapy. The PI3K/mTOR pathway is often upregulated in endocrine-resistant BC patients and, therefore, has been one of the targets for development of new agents. Recently, a Phase III trial (BOLERO-2) in aromatase inhibitor-resistant BC patients showed a significant improvement in time to progression with the combination of everolimus and exemestane compared with exemestane alone, confirming the importance of the PI3K/mTOR pathway in endocrine-resistant BC. Side effects from mTOR inhibitors are manageable, but early detection and proactive management are required to ensure patients’ safety, compliance and continuity of treatment. Thus, mTOR inhibitors offer a new hope and promise for patients with HR+ BC.

    Papers of special note have been highlighted as:

    • of interest

    •• of considerable interest

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