Originally published as JCO Early Release 10.1200/JCO.2008.16.8351 on March 2 2009

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Utility of Serum HER2 Extracellular Domain Assessment in Clinical Decision Making: Pooled Analysis of Four Trials of Trastuzumab in Metastatic Breast Cancer

From the Roche Products Ltd, Welwyn Garden City, United Kingdom; F Hoffmann-La Roche Ltd, Basel, Switzerland; Istituto Tumori, Milan, Italy; Hôpital Universitaire Saint Louis, Paris, France; Vall d'Hebron University Hospital, Barcelona, Spain; and the Emory University, Winship Cancer Institute, Atlanta, GA.

Corresponding author: Brian Leyland-Jones, PhD, Winship Cancer Institute, Emory University, School of Medicine, 1701 Uppergate Dr, Atlanta, GA 30322, USA; e-mail: LEYLAND{at}emory.edu.

Purpose Trastuzumab is a humanized monoclonal antibody directed against human epidermal growth factor receptor 2 (HER2). Trastuzumab alone or in combination with chemotherapy has been shown to be effective in patients with HER2-positive early and metastatic breast cancer. The extracellular domain (ECD) of the HER2 protein may be shed into the serum and is detectable using an enzyme-linked immunosorbent assay. Correlations have been reported between raised baseline ECD levels and response to trastuzumab, suggesting that serum ECD levels may be useful in making treatment decisions in patients with HER2-positive breast cancer. We investigated this relationship, and also the effect of trastuzumab and chemotherapy on ECD levels, in patients with advanced breast cancer.

Methods This study analyzed sequential ECD determinations on 322 patients treated with six different treatment regimens in four clinical trials.

Results Baseline values were available in 296 patients, and of these, 205 (69%) had raised levels (> 15 ng/mL). No clear relationship was found between baseline ECD levels and tumor response. After initiating combination therapy, ECD levels declined irrespective of treatment received and tumor response. For trastuzumab monotherapy, some trend between changes in ECD levels in early cycles and best response was discernable, but the overlap was too broad to be clinically useful. Disease progression was not reliably predicted by rising ECD levels in the majority of patients.

Conclusion Based on our data, we cannot recommend using serum HER2 ECD levels to make trastuzumab or other treatment decisions for individual patients with advanced/metastatic breast cancer.

Terms in blue are defined in the glossary, found at the end of this article and online at www.jco.org.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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