Breast Cancer
The Serum HER-2/neu Test and Metastatic Breast Cancer

Breast Cancer

Extensive studies have shown that HER-2/neu (c-erbB-2) positive breast cancer represents 20 to 30 percent of all breast cancers. Studies have shown that up to 90% of metastatic breast cancer patients can have an elevated Serum HER-2/neu level. In HER-2/neu positive breast cancer, the cancer cells have an abnormal level of HER-2/neu genes per cell, which leads to abnormally high levels of the HER-2/neu cancer-causing proteins called oncoproteins (overexpression). This causes the cancer cells to grow and divide quickly into more cancer cells. Overexpression of HER-2/neu has been shown to be an indicator of poor prognosis with patients exhibiting aggressive disease, decreased overall survival, and a higher probability of recurrence.2-3

The Siemens HER-2/neu test is the only Serum HER-2/neu test available for sale in the U.S. for measuring circulating levels of the HER-2/neu oncoprotein in the follow-up and monitoring of patients with metastatic breast cancer whose initial serum HER-2/neu is greater than 15 ng/mL. It is the only serum test available to monitor HER-2/neu baseline values and Serum HER-2/neu level changes over the course of the disease. Monitoring Serum HER-2/neu levels yields important information about response to therapy and cancer progression, and may help physicians make more informed decisions when developing and modifying patient treatment regimens.4-6

The HER-2/neu Oncoprotein

  • HER-2/neu is an oncoprotein, a class of proteins that are linked to tumor growth
  • 20 to 30 percent of all breast cancers are HER-2/neu (c-erbB-2) positive 2
  • HER-2/neu positive breast cancer cells have an abnormal number of HER-2/neu genes per cell, which leads to the production of abnormally high levels of HER-2/neu


Tissue and Serum HER-2/neu Testing

  • Traditional HER-2/neu status assessment has been generally limited to testing tissue from primary breast cancer
  • Serum HER-2/neu testing provides current or real-time assessment of a patient’s Serum HER-2/neu status with a minimally invasive procedure
  • Serum HER-2/neu testing enables physicians to:

        - Monitor changes in HER-2/neu levels over the course of metastatic disease
        - Assess response to treatment


Clinical Testing Algorithm

The Serum HER-2/neu test is for patients with metastatic breast cancer whose initial Serum HER-2/neu is greater than 15 ng/mL regardless of HER-2 positivity determined by tissue.

Serum HER-2/neu Testing Algorithm for Metastatic Breast Cancer (MBC) 7-11

Serum HER-2/neu Test Utility at a Glance

The Serum HER-2/neu test is used to monitor a patient’s HER-2/neu status once a diagnosis of metastatic breast cancer has been established. The chart above shows how the Serum HER-2/neu test is typically used as a monitoring tool complementary to tissue testing.

Complement Your Laboratory Menu with Serum HER-2/neu

The Serum HER-2/neu test from Siemens Healthcare Diagnostics measures circulating levels of the HER-2/neu oncoprotein. It is a simple blood test, with reliable and easily interpreted results. This assay is available on the automated ADVIA Centaur® System.

Performance Summary and Test Specificatons: ADVIA Centaur System

  • Sandwich immunoassay
  • Direct chemiluminescence technology
  • Normal cutoff value of 15 ng/mL
  • Two monoclonal antibodies that are specific for unique epitopes on the extracellular domain of the HER-2/neu oncoprotein
Sample Type Sample Test Volume Assay Range Analytical Sensitivity Calibration Interval Onboard Stability
Serum 20 µL 0.5-350 ng/mL 0.5 ng/mL 14 days 41 days

High Degree of Assay Performance and Clinical Reliability

  • Confidence in test results due to excellent precision and resistance to interference from HER-2/neu-based therapy6
  • Improved long-term patient monitoring due to low reagent lot-to-lot variability7
  • Broad assay range of 0.5 to 350 ng/mL
  • Excellent reproducibility with a Total % CV Range of 3.2% – 5.7%
  • 95% of normal patients have serum HER-2/neu levels below 15.2 ng/mL
  • Serial changes in HER-2/neu were correlated with changes in clinical status for all patients whose pre-treatment HER-2/neu values exceeded 15 ng/mL. For each pair of serial measurements, an increase of equal or greater than 15% was considered to indicate progression (predictive value of 67%). For each pair of serial measurements, a decrease of less than 15% was considered to indicate a lack of progression (predictive value of 71%).


1. Valero V, Roche H, Pienkowski T, et al. BCIRG 007: Serum HER-2/neu levels in women with metastatic HER-2/neu-amplified breast cancer. J Clin Oncol. ASCO Annual Meeting Proceedings 2007, Abstract No: 1020.
2. Slamon DJ, et al. Science 1987;235:177.
4. Schwartz MK, et al. International Journal of Biological Markers 2000;15(4):324.
5. Lipton A, et al. Journal of Clinical Oncology 2002;20(6):1467.
6. Esteva FJ, et al. Journal of Clinical Oncology 2002;20(7):1800.
7. Ali SM, Carney WP, Esteva FJ, et al. Serum HER-2/neu and relative resistance to trastuzumab-based therapy in patients with metastatic breast cancer. Cancer. 2008 Sep 15;113(6):1294-301.
8. Lipton A, Leitzel K, Chaudri-Ross HA, et al. Decrease in serum extracellular domain of HER2 at 4 and 8 weeks is associated with prolonged progression-free survival on lapatinib monotherapy. Proceedings of the 31st Annual CTRC-AACR San Antonio Breast Cancer Symposium, 2008. December: Abstract No. 3140.
9. Zidan J, Dashkovsky I, Stayerman C, et al. Comparison of HER-2 overexpression in primary breast cancer and metastatic sites and its effect on biological targeting therapy of metastatic disease. Br J Cancer. 2005 Sep 5;93(5):552-6.
10. Lower EE, Glass E, Blau R, Harman S. HER-2/neu expression in primary and metastatic breast cancer. 1: Breast Cancer Res Treat. 2009 Jan;113(2):301-6. Epub 2008 Feb 14.
11. Carney WP, Brown-Shimer S, Hamer PJ. Serum HER-2/neu testing can identify HER-2/neu positive patients previously classified as negative by tissue testing. American Association for Clinical Chemistry Annual Meeting Proceedings, 2008. Clin Chem Vol 54(56) Suppl, pg A130: Abstract No. C-96.

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