J Breast Cancer.  2014 Mar;17(1):33-39.

Serial Serum HER2 Measurements for the Detection of Breast Cancer Recurrence in HER2-Positive Patients

• Ha JH
• Seong MK
• Kim EK
• Lee JK
• Seol H
• Lee JY
• Byeon J
• Sohn YJ
• Koh JS
• Park IC
• Noh WC
• Kim HA

Abstract

PURPOSE
The measurement of serum human epidermal growth factor receptor 2 (HER2) extracellular domain levels is a well-established method for evaluating whether a metastatic HER2-positive breast cancer patient will respond to HER2-targeted treatment. However, little is known about the value of serum HER2 for detecting disease relapse following curative surgical treatment in breast cancer patients. The purpose of this study was to evaluate the sensitivity of serum HER2, carcinoembryonic antigen (CEA), and carcinoma antigen 15-3 (CA 15-3) for the detection of disease recurrence in postoperative breast cancer patients with a primary HER2-positive tumor.
METHODS
Serial measurements were taken of serum HER2, CEA, and CA 15-3 levels in patients with primary invasive HER2-positive breast cancer who underwent curative surgical treatment between January 2008 and December 2010. Following treatment, serum HER2 levels were monitored every 6 months using a chemiluminescence immunoassay.
RESULTS
Overall, 264 patients were analyzed in this retrospective study. The median follow-up period was 27.7 months, and 24 patients relapsed during follow-up. The sensitivity of serum HER2, CEA, and CA 15-3 for the detection of disease recurrence was 37.5%, 25.1%, and 12.5%, respectively. Sensitivity increased to 45.8% when all three tumor markers were combined in the analysis. In a subgroup of patients without liver disease, the sensitivity of serum HER2, CEA, and CA 15-3 was 57.1%, 21.4%, and 14.3%, respectively. Of the 264 patients in this study, 80 patients had chronic hepatitis, liver cirrhosis, or abnormal aspartate aminotransferase or alanine aminotransferase levels during the follow-up period. Following the exclusion of these patients, the sensitivity of serum HER2 for the detection of disease recurrence increased to 57.1%.
CONCLUSION
Serial serum HER2 measurement may be useful for the detection of disease relapse in patients with HER2-positive breast cancer. Abnormal liver function can result in elevated serum HER2 in the absence of disease recurrence.

Keyword

Breast neoplasms; Carcinoembryonic antigen; Carcinoma antigen 15-3; Human epidermal growth factor receptor 2; Tumor-associated antigen

MeSH Terms

Alanine Transaminase
Aspartate Aminotransferases
Breast Neoplasms*
Breast*
Carcinoembryonic Antigen
Follow-Up Studies
Hepatitis, Chronic
Humans
Immunoassay
Liver
Liver Cirrhosis
Liver Diseases
Luminescence
Receptor, Epidermal Growth Factor
Recurrence*
Retrospective Studies
Biomarkers, Tumor
Alanine Transaminase
Aspartate Aminotransferases
Carcinoembryonic Antigen
Receptor, Epidermal Growth Factor

Figure

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  Figure 1 Changes in serum human epidermal growth factor receptor 2 (HER2) levels at baseline and at the 6-month follow-up.

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  Figure 2 Changes in serum human epidermal growth factor receptor 2 (HER2) levels in patients with disease recurrence at follow-up. (A) Case I. A 26 years woman presented lung metastasis at 16 months after curative operation. At the time of disease relapse, elevated serum HER2 was observed. (B) Case II. A 54 year woman showed liver metastasis at 18 months after breast conservative surgery. Elevated serum HER2 level was checked at the time of diagnosis of disease relapse.

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  Figure 3 Receiver operating characteristic curve for serum human epidermal growth factor receptor 2 (HER2), carcinoembryonic antigen (CEA), and carcinoma antigen 15-3 (CA 15-3) levels.

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  Figure 4 Changes in serum human epidermal growth factor receptor 2 (HER2), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels in patients with elevated serum HER2 levels and no evidence of disease recurrence. (A)Case I. A 47 year patient presented mild fatty liver during the follow up period. The serum HER2, AST, ALT level has been changed simultaneously. During the follow up period, there was no evidence of disease recurrence. (B) Case II. A 45 year patient without any past history of liver disease showed elevated serum AST/ALT level. The serum HER2 level showed similar movement with the fluctuation of serum AST/ALT level. There was no evidence of disease relapse during follow up period.

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  Figure 5 The relationship between serum human epidermal growth factor receptor 2 (HER2) and serum aspartate aminotransferase (AST) (A) and alanine aminotransferase (ALT) (B).

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  Figure 6 Receiver operating characteristic (ROC) curve for serum human epidermal growth factor receptor 2 (HER2), carcinoembryonic antigen (CEA), and carcinoma antigen 15-3 (CA 15-3) levels in patients with normal aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels, chronic hepatitis, or liver cirrhosis.

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