HER2 Support Group Forums - Elissa - HER2 Serum Test Info

The following appeared in January 2006 CAP Today: HER2/neu
I read the article "IHC, FISH Still Sharing HER2 Spotlight" (August 2005) with great interest. As a practicing oncologist at the Charité in Berlin, Germany, I have a considerable amount of experience treating women with breast cancer. I am also familiar with the longstanding controversy surrounding IHC versus FISH for selecting patients to be treated with Herceptin. I rely on these methods to a great extent in my own practice.

I would like to point out another method that can be used for assessing HER2/neu status and for monitoring changes in HER2/neu. This is an FDA-cleared test that measures the extracellular domain of HER2/neu in the serum of breast cancer patients. This serum HER2/neu test (Bayer HealthCare, Diagnostics Division, Tarrytown, NY) has an established normal cutoff of 15 ng/mL. Numerous reports have shown that serum HER2/neu is elevated (>15 ng/mL) not only in metastatic breast cancer patients but also in a subset of women with primary breast cancer.1 I believe this should be considered in conjunction with IHC/FISH for assessing patients with breast cancer. According to my studies and publications, we have found, as have others, that over 50 percent of women with metastatic breast cancer can have an elevated serum HER2/neu level.2

More important, and related to your article, we have shown that there is a population of women that are HER2/neu-negative in the primary breast tumor, who are subsequently found to be HER2/neu-positive in the metastatic tumor by IHC/FISH methods.3 This has been confirmed by the recent Zidan, et al study.4

In addition, studies have also shown that there is a population of women with breast cancer (10-30 percent) that can be HER2/neu-negative by IHC/FISH in the primary tumor but have an elevated (>15 ng/mL) serum HER2/neu test during metastatic breast cancer.1 I believe this is a very important point because women who are designated HER2/neu-negative by tissue testing are not now eligible for Herceptin-based therapy, despite having a HER2/neu-positive tumor as evidenced by elevation of serum HER2/neu. Recent studies suggest that if you use the HER2/neu status as determined at the time of metastasis (regardless of HER2/neu status as determined at the time of primary disease), these patients also respond to Herceptin-based therapy.4-5

In summary, as a practicing oncologist, I think it is important to consider all three methods when assessing a patient's HER2/neu status. References
1. Carney WP, et al. Monitoring circulating levels of the HER-2/neu oncoprotein in breast cancer. Clin Breast Cancer. 2004;5(2):105-116.
2. Lueftner D, et al. Clin Biochem. 2003;36:233-240.
3. Lueftner D, et al. Breast Cancer Res Treat. 2004; 88(suppl1) 127. Abstract 3.45.
4. Zidan J, et al. Comparison of HER-2/neu expression in primary breast cancer and metastatic sites and its effect in biological targeting therapy of metastatic disease. Br J Cancer. 2005;10:1038-1046.
5. Meng S, et al. HER-2 gene amplification can be acquired as breast cancer progresses. PNAS. 2004;101(25): 9393-9398. PD Dr. med Diana Lüftner
Department of Oncology and Hematology
Humboldt-University Berlin
Germany