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Serum HER-2: sensitivity, specificity, and predictive values for detecting metastatic recurrence in breast cancer patients

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Abstract

Purpose

The aim of this study was to determine the sensitivity, specificity, and predictive values of serum HER-2 for detecting metastatic recurrence in breast cancer patients.

Methods

In the period 2004–2009, serum HER-2 was measured in 1,348 patients with breast cancer: 837 during routine controls at the Oncology Department and 511 newly diagnosed. The patients with positive serum HER-2, all the newly diagnosed and 1/5 of the patients with negative serum HER-2 were followed with serum HER-2 measurements every 3–12 months using the ADVIA Centaur assay. Tissue HER-2 status was determined by IHC and FISH. Patients with a single serum HER-2 value above 15 μg/L were considered serum positive. Metastases were diagnosed according to the routine clinical methods using imaging/biopsy.

Results

Of the 862 patients included, 21 had unavailable medical records and were excluded. Patients with unknown tissue status (218), missing blood sample before recurrence (74), or presenting with primary metastatic disease (9) were also excluded. Blood samples before the detection of metastatic recurrence were available in 154 tissue HER-2-positive and in 386 tissue HER-2-negative patients. The sensitivity, specificity, positive and negative predictive values in tissue HER-2-positive patients with values above 15 μg/L were 69 % (95 % CI 53–80 %), 71 % (62–78), 47 % (35–59), and 86 % (77–91), respectively. Combining the cutoff value of 15 μg/L with a delta value of >100 % increase from individual baseline after primary therapy, or increasing the cutoff to 32 μg/L raises the specificity to 96 %, but lowers the sensitivity to 50 and 47 %, respectively. Preoperative serum HER-2 values were accessible in 69 tissue-positive patients, but no significant association was found with later development of metastases. The sensitivity, specificity, positive and negative predictive values in tissue HER-2-negative patients with values above 15 μg/L were 33 % (21–47), 77 % (73–82), 18 % (12–27), and 88 % (84–91), respectively.

Conclusions

Monitoring tissue HER-2-positive breast cancer patients with serum HER-2 has a sufficient sensitivity to detect metastatic recurrence, while its use in monitoring of tissue HER-2-negative patients is unsatisfactory.

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Abbreviations

HER-2:

Human epidermal growth factor receptor 2

ECD:

Extracellular domain

IHC:

Immunohistochemistry

FISH:

Fluorescence in situ hybridization

FEC:

Fluorouracil, epirubicin, cyclophosphamide

CT/UL/MR:

Computed tomography/ultrasound/magnetic resonance

HNU:

Human neu unit

CA 15-3:

Cancer antigen 15-3

CEA:

Carcinoembryonic antigen

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Acknowledgments

The Research Fund at Vejle Hospital, University of Southern Denmark and Plum A/S Denmark financed this work. We would like to thank the laboratory technologists Sara Egsgaard and Camilla Davidsen for their excellent work. Test kits used for HER-2 serum measurements were partially provided by Siemens.

Conflict of interest

  Ivan Brandslund received honoraria for 2 lectures on serum HER-2 from Siemens Denmark.

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Authors and Affiliations

  1. Department of Clinical Biochemistry, Lillebaelt Hospital, Kabbeltoft 25, 7100, Vejle, Denmark

    Patricia Diana Sørensen, Jonna Skov Madsen, Eva Brix Petersen, Rikke Fredslund Andersen & Ivan Brandslund

  2. Faculty of Health Sciences, Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark

    Patricia Diana Sørensen, Jonna Skov Madsen & Ivan Brandslund

  3. Department of Clinical Oncology, Lillebaelt Hospital, Vejle, Denmark

    Erik Hugger Jakobsen

  4. Department of Clinical Pathology, Lillebaelt Hospital, Vejle, Denmark

    Birthe Østergaard

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  1. Patricia Diana Sørensen
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Correspondence to Patricia Diana Sørensen.

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Sørensen, P.D., Jakobsen, E.H., Madsen, J.S. et al. Serum HER-2: sensitivity, specificity, and predictive values for detecting metastatic recurrence in breast cancer patients. J Cancer Res Clin Oncol 139, 1005–1013 (2013). https://doi.org/10.1007/s00432-013-1411-7

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  • DOI: https://doi.org/10.1007/s00432-013-1411-7

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