Serum HER-2 predicts response and resistance to trastuzumab treatment in breast cancer

Eva Rabing Brix Petersen; Patricia Diana Sørensen; Erik Hugger Jakobsen; Jonna Skov Madsen; Ivan Brandslund

doi:10.1515/cclm-2012-0558

Article

Serum HER-2 predicts response and resistance to trastuzumab treatment in breast cancer

Eva Rabing Brix Petersen , Patricia Diana Sørensen , Erik Hugger Jakobsen , Jonna Skov Madsen and Ivan Brandslund

Published/Copyright: February 18, 2013

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From the journal Clinical Chemistry and Laboratory Medicine Volume 51 Issue 7

Abstract

Background: Serum HER2 (S-HER2) was approved in 2003 by the US Food and Drug Administration (FDA) for monitoring trastuzumab treatment in tissue HER2 positive breast cancer patients. Information of the value of S-HER2 is scarce. We hypothesised that S-HER2 would reflect the clinical effect of trastuzumab.

Methods: We followed 48 patients eligible for trastuzumab treatment for up to 6 years or until death. S-HER2 was measured on an ADVIA Centaur System and S-Trastuzumab was measured by an in-house developed fluorescent enzyme immunoassay system on the ImmunoCap 100.

Results: A decrease in S-HER2 of ≥20% was correlated to no progression in the disease in 20 out of 21 clinical courses (p<0.0001). An increase in S-HER2 of ≥20% was correlated to progression in the disease in 40 out of 44 clinical courses (p<0.0001). Patients with no recurrence after trastuzumab treatment (n=18) had a median S-HER2 concentration of 10.5 μg/L, whereas patients alive with recurrence (n=13) had a median S-HER2 of 20.1 μg/L (p=0.002). Patients who died prompted by recurrence (n=17) had a median S-HER2 of 232.4 μg/L at latest measurement before death (p=<0.0001) compared to patients without recurrence. In two patients with S-HER2 values above 1000 μg/L the concentrations of S-trastuzumab were measured below the target trough concentration in serum of 10 mg/L.

Conclusions: Decreasing values of S-HER2 predicts response to treatment whereas increasing levels predict resistance. S-HER2 above 1000 μg/L warns that standard doses of trastuzumab may be insufficient as reflected by low concentrations of S-trastuzumab.

Keywords: breast cancer; clinical outcome; ErbB2; Herceptin®; HER2; trastuzumab

Corresponding author: Eva Rabing Brix Petersen, Department of Clinical Biochemistry, Lillebaelt Hospital, Vejle, Kabbeltoft 25, 7100 Vejle, Denmark, Phone: +45 79 406500, Fax: +45 79 406871

The authors would like to thank Peer Horn, PhD student, Department of Clinical Biochemistry, for valuable laboratory help and advice, Camilla Davidsen and Sara Egsgaard, Department of Clinical Biochemistry, for excellent laboratory work and Gitte Møller, Department of Oncology, for providing relevant patient details.

Conflict of interest statement

Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article.

Research funding: None declared.

Employment or leadership: Ivan Brandslund has received compensation from Siemens for lecturing on S-HER2 for customers and employees.

Honorarium: None declared.

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Received: 2012-8-30

Accepted: 2013-1-17

Published Online: 2013-02-18

Published in Print: 2013-07-01

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Articles in the same Issue

https://doi.org/10.1515/cclm-2012-0558

Keywords for this article

breast cancer; clinical outcome; ErbB2; Herceptin®; HER2; trastuzumab