HER-2 is the abbreviation for Human Epidermal Growth Factor Receptor 2. The HER-2/neu gene encodes 1 of 4 transmembrane receptor protein-tyrosine kinases that mediate cell growth, differentiation, and survival. HER-2/neu gene overexpression or amplification is found in ~20% of breast tumors and is associated with agressive disease and a higher rate of recurrence and mortality. Of 25,000 patients with HER-2/neu positive tumors have shorter disease free survival overall survival regardless of other prognostic indicators and lymph node status. Because of these factors, ASCO & CAP recommend that all tumors be tested for it.1
The serum HER-2/neu test was cleared in 2000 by the FDA for the management and monitoring of women with metastatic breast cancer, however, it should be noted that many clinical research studies have shown that women with early breast cancer can also have elevated ( greater than 15 ng/ml) serum HER-2/neu levels.
The serum HER-2/neu test is a simple blood test and it specifically measures the levels of the HER-2 protein released by the cell into the blood. Normal breast cells release the HER-2 protein into the blood. The normal level is less than 15 ng/ml. Patients should considered any number less than 15 ng/ml as normal and it doesn’t matter if the patient is 8,10, 12, or 14. The blood test is very simple and the test needs very little blood to measure the amount of the HER-2 protein in the blood. Increasing levels of the HER-2/neu protein in the blood reflects tumor progression while decreasing levels reflect response of the tumor to therapy.
ASCO does not endorse the use of any tumor markers or the HER-2/neu oncoprotein, however, in the Jan 2007 issue of the Journal of Clinical Oncology guidelines were published which provided a substantial summary of the serum HER-2/neu data indicating the importance of the test. There is a substantial amount of data and information published on the serum HER-2/neu test which patients should offer to their oncologist to read. Physicians The serum HER-2/neu test is an additional tool for managing breast cancer patients and should always be used in conjunction with other diagnostic tools. Some women that are said to be negative for a HER-2 by tissue testing (IHC or FISH) can have elevated serum HER-2 levels at the time of metastatic breast cancer. Women with elevated levels and a negative tissue test should have their original tumor re-tested by IHC or FISH or a biopsy of a metastatic tumor to check the HER-2/neu status. More education is needed to inform breast cancer oncologists, so they will know that the test is available, is standardized, is FDA cleared and is reliable. Serum HER-2/neu levels will fluctuate depending on the behavior of the tumor in response or lack of response to therapies. The test should be done on all women with metastatic breast cancer and repeated 3 or 4 times a year. The test is dynamic and changes with growth of the tumor or the shrinking of the tumor. The test is a real time test and will help physicians manage patients with HER-2 positive tumors since increasing levels reflect cancer progression while decreasing levels reflect the response of the tumor to treatment.
1 AmericanSociety of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. Arch Pathol Lab Med. 2007;131:18-43.