HER2 testing in breast cancer: Opportunities and challenges

Human epidermal growth factor receptor 2 (HER2) is overexpressed in
15-25% of breast cancers, usually as a result of HER2 gene
amplification. Positive HER2 status is considered to be an adverse
prognostic factor. Recognition of the role of HER2 in breast cancer
growth has led to the development of anti-HER2 directed therapy,
with the humanized monoclonal antibody trastuzumab (Herceptin (R))
having been approved for the therapy of HER2-positive metastatic
breast cancer. Clinical studies have further suggested that HER2
status can provide important information regarding success or
failure of certain hormonal therapies or chemotherapies. As a
result of these developments, there has been increasing demand to
perform HER2 testing on current and archived breast cancer
specimens. This article reviews the molecular background of HER2
function, activation and inhibition as well as current opinions
concerning its role in chemosensitivity and interaction with
estrogen receptor biology. The different tissue-based assays used
to detect HER2 amplification and overexpression are discussed with
respect to their advantages and disadvantages, when to test (at
initial diagnosis or pre-treatment), where to test (locally or
centralized) and the need for quality assurance to ensure accurate
and valid testing results.