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

다국어 초록 (Multilingual Abstract)

Purpose: The measurement of serum human epidermal growthfactor receptor 2 (HER2) extracellular domain levels is a wellestablishedmethod for evaluating whether a metastatic HER2-positive breast cancer patient will respond to HER2-targetedtreatment. However, little is known about the value of serumHER2 for detecting disease relapse following curative surgicaltreatment in breast cancer patients. The purpose of this studywas to evaluate the sensitivity of serum HER2, carcinoembryonicantigen (CEA), and carcinoma antigen 15-3 (CA 15-3) for the detectionof disease recurrence in postoperative breast cancer patientswith a primary HER2-positive tumor. Methods: Serial measurementswere taken of serum HER2, CEA, and CA 15-3 levelsin patients with primary invasive HER2-positive breast cancerwho underwent curative surgical treatment between January2008 and December 2010. Following treatment, serum HER2levels were monitored every 6 months using a chemiluminescenceimmunoassay. Results: Overall, 264 patients were analyzedin this retrospective study. The median follow-up periodwas 27.7 months, and 24 patients relapsed during follow-up. Thesensitivity of serum HER2, CEA, and CA 15-3 for the detection ofdisease recurrence was 37.5%, 25.1%, and 12.5%, respectively.
Sensitivity increased to 45.8% when all three tumor markerswere combined in the analysis. In a subgroup of patients withoutliver disease, the sensitivity of serum HER2, CEA, and CA 15-3was 57.1%, 21.4%, and 14.3%, respectively. Of the 264 patientsin this study, 80 patients had chronic hepatitis, liver cirrhosis, orabnormal aspartate aminotransferase or alanine aminotransferaselevels during the follow-up period. Following the exclusion ofthese patients, the sensitivity of serum HER2 for the detection ofdisease recurrence increased to 57.1%. Conclusion: Serial serumHER2 measurement may be useful for the detection of diseaserelapse in patients with HER2-positive breast cancer. Abnormalliver function can result in elevated serum HER2 in the absenceof disease recurrence.

참고문헌 (Reference)

1 Andrulis IL, "neu/erbB-2 amplification identifies a poor-prognosis group of women with node-negative breast cancer. Toronto Breast Cancer Study Group" 16 : 1340-1349, 1998

2 Molina R, "Use of serial carcinoembryonic antigen and CA 15.3 assays in detecting relapses in breast cancer patients" 36 : 41-48, 1995

3 Duffy MJ, "Serum tumor markers in breast cancer: are they of clinical value?" 52 : 345-351, 2006

4 Motoo Y, "Serum levels of c-erbB-2 protein in digestive diseases" 29 : 616-620, 1994

5 Molina R, "Serum levels of C-erbB-2 (HER-2/neu) in patients with malignant and non-malignant diseases" 18 : 188-196, 1997

6 Pedersen AC, "Sensitivity of CA 15-3, CEA and serum HER2 in the early detection of recurrence of breast cancer" 51 : 1511-1519, 2013

7 Fehm T, "Prognostic significance of serum HER2 and CA 15-3 at the time of diagnosis of metastatic breast cancer" 24 (24): 1987-1992, 2004

8 Schwartz MK, "Monitoring therapy by serum HER-2/neu" 15 : 324-329, 2000

9 Nahta R, "Mechanisms of disease: understanding resistance to HER2-targeted therapy in human breast cancer" 3 : 269-280, 2006

10 류동원, "Impact of Serum HER2 Levels on Survival and Its Correlation with Clinicopathological Parameters in Women with Breast Cancer" 한국유방암학회 15 (15): 71-78, 2012

11 Baxevanis CN, "Immunobiology of HER-2/neu oncoprotein and its potential application in cancer immunotherapy" 53 : 166-175, 2004

12 Slamon DJ, "Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene" 235 : 177-182, 1987

13 Gerhardt W, "Evaluation of test data from clinical studies. I. Terminology, graphic interpretation, diagnostic strategies, and selection of sample groups. II. Critical review of the concepts of efficiency, receiver operated characteristics (ROC), and likelihood ratios" 181 : 1-74, 1986

14 Sugano K, "Combined measurement of the c-erbB-2 protein in breast carcinoma tissues and sera is useful as a sensitive tumor marker for monitoring tumor relapse" 89 : 329-336, 2000

15 Cook GB, "Clinical utility of serum HER-2/neu testing on the Bayer Immuno 1 automated system in breast cancer" 21 (21): 1465-1470, 2001

16 Baskić D, "Clinical evaluation of the simultaneous determination of CA 15-3, CA 125and sHER2 in breast cancer" 12 : 657-667, 2007

17 Molina R, "C-erbB-2, CEA and CA 15.3 serum levels in the early diagnosis of recurrence of breast cancer patients" 19 (19): 2551-2555, 1999

18 Harris L, "American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer" 25 : 5287-5312, 2007