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New and emerging treatments for estrogen receptor-positive breast cancer: focus on everolimus

Authors Paplomata E, O'Regan R

Received 16 October 2012

Accepted for publication 11 December 2012

Published 14 January 2013 Volume 2013:9 Pages 27—36


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Peer reviewer comments 6

Elisavet Paplomata, Ruth O’Regan

Department of Hematology and Medical Oncology, Winship Institute of Emory University, Atlanta, GA, USA

Abstract: Management of patients with metastatic hormone receptor-positive breast cancer poses a challenge due to the inevitable development of endocrine resistance. Hormone resistance is associated with a complex interaction of the estrogen receptor with growth factors, transmembrane receptors, and intracellular growth cascades. The PI3K/Akt/mTOR pathway plays a major role in hormone resistance and proliferation of breast cancer. Preclinical and clinical data indicate that inhibitors of human epidermal growth factor receptor-2, epidermal growth factor receptor, insulin-like growth factor-1 receptor, and the mammalian target of rapamycin pathway may act synergistically with hormone therapy to circumvent endocrine resistance. Everolimus is currently approved for combination with exemestane in postmenopausal women with advanced hormone receptor-positive breast cancer. However, we still need to unfold the full potential of targeted agents in the hormone-refractory setting and to identify the subsets of patients who will benefit from combination hormonal therapy using targeted agents.

Keywords: everolimus, estrogen receptor-positive breast cancer, hormone resistance, mammalian target of rapamycin, inhibition

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