HER2 is one of a handful of breast cancer biomarkers used for clinical decision making. Breast cancer patients whose tumor tissue samples have a positive HER2 status may be offered anti-HER2 targeted therapies such as Trastuzumab or Lapatinib. The American Society of Clinical Oncology (ASCO) and College of American Pathologists (CAP) released updated guidelines on HER2 testing in breast cancer in 2013. The guidelines recommend HER2 tissue testing, using immunohistochemistry (IHC), fluorescence in-situ hybridization (FISH) or bright-field ISH.1

That same year, Carney and colleagues2 proposed that periodic monitoring of serum HER2 (serumHER2) levels in all breast cancer patients provides important information for patient management. To build their case, they reviewed the published findings on thousands of patients who have undergone serumHER2 testing since 2007. They limited their review to peer reviewed publications which specifically employed quantitative and standardized serumHER2 tests with clearly defined limits and a definition of what constitutes a significant change in serumHER2 levels. In their review they describe HER2 tissue testing challenges, summarize published serumHER2 data and address testing controversies.

Carney et al.2 demonstrated that on average, about 20% of the breast tumors classified as HER negative by tissue testing are misclassified. Tumor tissue is heterogeneous and the cut-off levels distinguishing a HER2 positive from a HER2 negative tumor can be ambiguous. As a result, misclassified patients may miss out on therapeutic opportunities and may go on to develop HER2 positive recurrent breast cancer. Serum HER2 testing may help identify the patients initially misclassified as HER2 negative by tissue testing.

In addition, the review suggests that serum HER2 monitoring may be an effective way to monitor HER2 positive patients. The rise and fall of serumHER2 levels in the serum parallel the clinical course of disease. The authors review the data showing that increases in circulating HER2 are an early indicator of progression, especially in patients who are HER2 positive. They describe the studies indicating the prognostic value of serumHER2, especially in association with shorter disease-free survival.

Related:  Tissue-Based Diagnostic Tests for HER-2 in Breast Cancer

The main point of this review is that the serumHER2 test is complementary to the HER2 tissue tests. The authors make a compelling argument to support periodic serumHER2 monitoring for all breast cancer patients; serumHER2 testing can be used to help identify patients with latent HER2 positive status and to monitor changes in serumHER2 that may indicate disease changes. The review also emphasizes the importance of using a standardized and validated assay, as many of the earlier studies used research-only assays that were not standardized or validated by acceptable diagnostic protocols and procedures.

What will be the future testing recommendations? The ASCO Expert Panel will be releasing a new guideline for Biomarkers for Adjuvant and Metastatic Breast Cancer later this year.3 In addition to examining the role of HER2, estrogen receptor (ER), and progesterone receptor (PgR), for clinical decision-making, the panel for the guideline on early-stage invasive breast cancer is studying a set of 11 tumor and blood biomarkers.

  1. ASCO and the CAP Release Updated Guideline on HER2 Testing in Breast Cancer (October 7, 2013) http://www.asco.org/press-center/asco-and-cap-release-updated-guideline-her2-testing-breast-cancer
  1. Carney WP, Bernhardt D, Jasani B. Circulating HER2 Extracellular Domain: A Specific and Quantitative Biomarker of Prognostic Value in all Breast Cancer Patients? (2013) Biomarkers in Cancer 12;5:31-9.
  1. ASCO Creating Guidelines for Management of Metastatic and Early-Stage Invasive Breast Cancer (May 30, 2015) https://am.asco.org/asco-creating-guidelines-management-metastatic-and-early-stage-invasive-breast-cancer