[Clinical usefulness of circulating ECD/HER-2 measurement for breast cancer patients' management]

Abstract

Background: About 15 to 20% of breast cancer cases overexpress human epidermal growth factor receptor-2 (HER-2). This overexpression is associated with poor clinical prognosis but therapeutic success of trastuzumab or lapatinib. HER-2 extracellular domain (ECD) undergoes a proteolytic cleavage and is shed into biologic fluid as a circulating antigen called ECD/HER-2, which can be detected by immunochemical assays.

Objective: The aim of our review was to determine the clinical usefulness of ECD/HER-2 measurement in the management of breast cancer patients.

Material and methods: A Pubmed search for publications in English or French was carried out until March 31, 2010 (69 original articles and 8 reviews).

Results: The measurement of ECD/HER-2 concentration does not exempt from the pathological determination of HER-2 expression in tumors; some HER-2 negative tumors are associated with high levels of ECD/HER-2, on the other hand, some HER-2 positive tumors present low levels of ECD/HER-2. The concentration of ECD/HER-2 is correlated to disease progression, since 10% of loco-regional breast cancers and more than a third of metastatic breast cancers have high levels of ECD/HER-2. The elevation of ECD/HER-2 levels generally occurs several months before the diagnosis of symptomatic metastases. The relevance of ECD/HER-2 measurements during chemotherapy, hormone therapy and trastuzumab treatment remains uncertain. Similarly, it is not commonly agreed that high levels of ECD/HER-2 before any treatment in the case of an early breast cancer, is an independent prognostic factor.

Discussion: A close analysis of a variety of pathological, biochemical, clinical and methodological data may explain these discrepancies.

Conclusion: New prospective studies using immunochemical measurements of ECD/HER-2 (with a consensual threshold) and based on both detailed pathological analyses and a comprehensive collection of clinical data are still required to establish the clinical usefulness of circulating ECD/HER-2 measurement for breast cancer patients' management.