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What does the test tell him and her: HER-2/neu testing. Part II:

© Laura Ruth

"What do the results mean?" might be the question which pops into your head after you receive either negative or positive results back from any HER-2/neu diagnostic test. Currently the HER-2/neu gene or protein are used for prognosis and therapy options for breast cancer. According to cytogeneticist Rhona Schreck at Cedars-Sinai Medical Center and in much of the medical community, it is generally believed that a high level of HER-2/neu expression predicts a shortened disease-free survival, higher probability of tumor recurrence, and poor clinical outcome.

Even though the increased level of HER-2/neu protein reports a looming message, the levels of HER-2/neu protein, both increased and decreased, can be used to choose therapy options or rationalize therapeutic responses. A patient with increased levels of the HER-2/neu protein is a candidate for treatment with HerceptinTM. HerceptinTM is an antibody based treatment that prevents the cancerous cells from proliferating by binding to the protein and preventing the cellular growth mechanism. HerceptinTM can be used alone or in combination with other chemotherapies.

Ross and Fletcher recently surveyed the current literature on patients with HER-2/neu abnormalities and the patient's response to therapy. The trends they found about the various therapy options includes information about hormonal therapy, i.e. tamoxifen, CMF (cytoxan, methotrexate, 5-fluorouracil) adjuvant chemotherapy, paclitaxel (Taxol), doxorubicin (Adriamycin), CAFT (cisplatin, Adriamycin [doxorubicin], fluorouracil, teniposide), and surgery. HER-2/neu positive tumors are sometimes resistant to hormonal therapy, CMF adjuvant therapy, and sometimes Taxol. Interestingly, in one 20-year follow up chemotherapy study, HER-2/neu tumors treated with tamoxifen had an adverse outcome versus untreated tumors. At this point the literature indicates that some HER-2/neu positive tumors have an enhanced response rate to doxorubicin and the anti-topoisomerase drug epirubicin. According to Dr. Jeffrey Ross, a pathologist at the Albany Medical College and Consultant Medical Director of Ventana Medical Systems, Inc., "HER-2 testing is used to avoid tamoxifen alone in node-negative cases not getting cytotoxic adjuvant therapy. It is also used to select for adriamycin regimens in adjuvant settings." Although the literature review found strong trends in positive and negative responses to various therapies, further studies are required to make firmer conclusions.

Literature References

http://www.ncbi.nlm.nih.gov/htbin-post/E... HER-2/neu gene amplification by fluorescence in situ hybridization allows risk-group assessment in node-negative breast cancer. Harbeck, N. et al, International Journal of Oncology, 14: 663-671, 1999.

http://www.ncbi.nlm.nih.gov/htbin-post/E... Detection and quantitation of HER-2/neu gene amplification in human breast cancer archival material using fluorescence in situ hybridization. Pauletti, G., et al, Oncogene, 13(1): 63-72, 1996.

http://www.ncbi.nlm.nih.gov/htbin-post/E... HER-2/neu as a predictive marker of response to breast cancer therapy. Pegram, M.D., et al, Breast Cancer Research and Treatment 52: 65-77, 1998.