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International Journal of Breast Cancer
Volume 2013, Article ID 137414, 15 pages
Review Article

Drug Resistance and the Role of Combination Chemotherapy in Improving Patient Outcomes

Breast Cancer Research, Sarah Cannon Research Institute, 250 25th Avenue North, Suite 110, Nashville, TN 37203, USA

Received 26 February 2013; Accepted 1 May 2013

Academic Editor: Ian S. Fentiman

Copyright © 2013 Denise A. Yardley. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Resistance to cancer chemotherapy is a common phenomenon especially in metastatic breast cancer (MBC), a setting in which patients typically have had exposure to multiple lines of prior therapy. The subsequent development of drug resistance can result in rapid disease progression during or shortly after completion of treatment. Moreover, cross-class multidrug resistance limits patient treatment choices, particularly in a setting where treatments options are few. One attempt to minimize the impact of drug resistance has been the concurrent use of two or more chemotherapy agents with unrelated mechanisms of action and differing modes of drug resistance, with the intent of blocking the development of multiple intracellular escape pathways essential for tumor survival. Within the past decade, an array of mechanistically diverse agents has augmented the list of combination regimens that may be both synergistic and efficacious in pretreated MBC. The aim of this paper is to review mechanisms of resistance to common chemotherapy agents and to consider current combination treatment options for heavily pretreated and/or drug-resistant patients with MBC.