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Precision medicine and personalized breast cancer: combination pertuzumab therapy

Authors Reynolds K, Sarangi S, Bardia A, Dizon D

Received 12 October 2013

Accepted for publication 28 November 2013

Published 20 March 2014 Volume 2014:7 Pages 95—105


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 4

Video abstract presented by Reynold K, Sarangi S, Bardia A, and Dizon DS.

Views: 296

Kerry Reynolds, Sasmit Sarangi, Aditya Bardia, Don S Dizon

Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA

Abstract: Trastuzumab (Herceptin), a monoclonal antibody directed against the human epidermal growth-factor receptor 2 (HER2), is the poster child for antibody-based targeted therapy in breast cancer. Pertuzumab, another humanized monoclonal antibody, binds to a different domain of HER2 and prevents the formation of HER2:HER3 dimers, which is the most potent heterodimer in the HER family. The combination of trastuzumab and pertuzumab has synergistic activity, and is associated with improved clinical outcomes. The US Food and Drug Administration (FDA) approved pertuzumab in combination with trastuzumab-based chemotherapy originally as first-line therapy for metastatic HER2-positive breast cancer in 2012, and more recently as neoadjuvant therapy for localized disease in 2013. Pertuzumab is the first neoadjuvant drug to receive accelerated approval by the FDA based on pathological complete response as the primary end point. In this article, we review the mechanism of action, pharmacokinetics, clinical efficacy, safety, and current role of pertuzumab in the management of breast cancer, as well as ongoing clinical trials and future directions regarding the utility of pertuzumab as a personalized therapeutic option for HER2-positive breast cancer. In the coming years, we anticipate increased utilization of neoadjuvant trials for drug development, biomarker discovery, and validation, and envision conduct of personalized breast cancer clinics in which therapies will be routinely selected based on genetic alterations in the tumor. Regardless of the targeted therapy combinations employed based on tumor genomic profile, trastuzumab and pertuzumab will likely continue to form the backbone of the personalized regimen for HER2-positive breast cancer.

Keywords: pertuzumab, HER2 breast cancer, personalized therapy, precision medicine

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