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HER2 and predicting response to therapy in breast cancer

Authors
Hideko Yamauchi, MD
Daniel F Hayes, MD
Section Editor
Harold Burstein, MD, PhD
Deputy Editor
Sadhna R Vora, MD

INTRODUCTION

Here we will review the relationship between expression of human epidermal growth factor receptor 2 (HER2) and response to endocrine therapy, chemotherapy, and HER2-directed therapies in the adjuvant setting and in women with advanced disease.

THE HER2 ONCOGENE

The human epidermal growth factor receptor 2 (HER2) oncogene encodes for a 185 KD transmembrane glycoprotein receptor with intracellular tyrosine kinase activity [1]. The HER2 receptor belongs to the epidermal growth factor receptor (EGFR) family of receptors, which are critical in the activation of subcellular signal transduction pathways controlling epithelial cell growth and differentiation [2,3] and possibly angiogenesis [4,5]. HER2, the epidermal growth factor receptor 2, was previously called HER2/neu, or ERBB-2. Amplification of HER2 or overexpression of its protein product is observed in 18 to 20 percent of human breast cancers [6-8].

Clinical utility of HER2 testing — Several guideline bodies, including the American Society of Clinical Oncology (ASCO), the College of American Pathologists (CAP), the National Comprehensive Cancer Network (NCCN), and the UK National HER2 Reference Laboratory, among others, recommend routine testing of human epidermal growth factor receptor 2 (HER2) expression on newly diagnosed and metastatic breast cancers [9-12] because HER2 status is a predictive factor in breast cancer:

High levels of HER2 expression identify those women who benefit from treatment with agents that target HER2. For example, trastuzumab is remarkably effective both as monotherapy and in combination with cytotoxic chemotherapy in patients with HER2-positive metastatic disease. Furthermore, multiple randomized trials indicate a significant survival benefit when this drug is applied in the adjuvant setting for HER2-positive breast cancer. (See "Adjuvant systemic therapy for HER2-positive breast cancer".)

HER2 status appears to predict resistance or sensitivity to different types of chemotherapeutic agents, including anthracyclines and taxanes. (See 'Response to chemotherapy' below.)

HER2 positivity may be associated with resistance to endocrine therapies. At least some data suggest that this effect may be specific to selective estrogen modulator (SERM) therapy (eg, tamoxifen) and perhaps not to estrogen depletion therapies (eg, aromatase inhibitors), although the data are conflicting [13]. (See 'Response to endocrine therapy' below.)

             

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Literature review current through: Nov 2016. | This topic last updated: Mon Jan 11 00:00:00 GMT+00:00 2016.
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