The National Comprehensive Cancer Network (NCCN) has updated its Practice Guidelines in Oncology to indicate that fluorescence in situ hybridization (FISH), the diagnostic technology used in Abbott's Vysis PathVysion test, may be more accurate than immunohistochemistry (IHC), the most commonly used test method for determining HER2 status in women with metastatic breast cancer.
The NCCN is a not for profit, tax-exempt corporation that is an alliance of the world's leading cancer centers. The organization's Clinical Practice Guidelines in Oncology are widely recognized and used as the standard for clinical policy in cancer care, and are the only comprehensive set of guidelines updated annually by any national organization in any area of medicine.
"The new guidelines on HER2 testing will help ensure that physicians and patients have the most accurate information when deciding on the best course of treatment for this life-threatening disease," said Steven Seelig, M.D., Ph.D., divisional vice president, Vysis research and development, Abbott Laboratories. "As a highly accurate test for HER2 diagnosis, PathVysion is a vital tool in the fight against breast cancer."
PathVysion, designed to detect amplification of the HER2 gene in breast cancer tissue specimens, is used to identify which women are potential candidates for Herceptin, a unique monoclonal therapy that specifically targets tumor cells that overexpress the HER2 protein. It is the only FISH-based test the U.S. Food and Drug Administration (FDA) has approved for inclusion in the Herceptin package insert for the selection of patients who may respond to treatment. In addition to Herceptin therapy selection, PathVysion is also used for assessing patient prognosis and response to Adriamycin-based therapies, making it the only HER2 assessment method approved for these three claims.
In 25 to 30 per cent of breast cancer patients, the presence of multiple copies of the HER2 gene on a single chromosome, called "gene amplification," leads to overexpression of HER2 protein, which plays a pivotal role in the rapid growth of tumor cells. Determination of HER2 gene status is critical for selecting therapeutic options. HER2 status indicates the likelihood of response to certain chemotherapeutic agents, aids in assessing patient prognosis, and identifies patients who may respond to Herceptin. FISH testing measures the number of copies of the HER2 gene at the DNA level. Using fluorescent coloring and a microscope, physicians can count the actual number of HER2 genes present in the cell nucleus. In comparison, IHC-based tests measure HER2 protein overexpression, making the interpretation of results subjective.
"Personalized treatment begins with an accurate diagnosis," said Mark Pegram, M.D., associate professor of medicine, Division of Hematology/Oncology, and director of the Women's Cancer Program, UCLA/Jonsson Comprehensive Cancer Center. "We rely on PathVysion to determine a woman's HER2 status because it reduces false negatives and false positives, clearly differentiating those patients who will most likely respond to Herceptin from those who may not. By using PathVysion, physicians can make better treatment decisions that may extend a patient's survival."
In the past, NCCN guidelines have addressed the importance of HER2 testing and available diagnostic options. This is the first year the organization specifically calls attention to the accuracy of FISH versus IHC. While acknowledging differences in cost, the guidelines state that available data suggest that amplified HER2 by FISH analysis is a better predictor that patients will respond to Herceptin therapy than those with HER2 expression of 2+ determined by IHC.
Results from the IHC test are reported as O, 1+, 2+, or 3+. Tumors with a 3+ score from an IHC test are considered HER2 positive. Tumors with IHC 2+ scores are considered borderline and, therefore, subject to interpretation. IHC results are subjectively scored by interpreting tissue color change, and can be affected by tissue processing techniques and antibody sensitivity. By contrast, PathVysion's FISH technology offers objective, quantitative results. The test contains a second, built-in control probe specific for chromosome 17, where the HER2 gene resides. This control probe helps to achieve more accurate results because the reader directly counts HER2 gene copies and control probes at the same time.
"One false result can have a devastating impact on a patient and their loved ones, which is why we educate patients about the most accurate diagnostic tools available," said Karlynn BrintzenhofeSzoc, DSW, president-elect of the Association of Oncology Social Work, who recently developed a training program to help members understand the role of molecular diagnostics in cancer treatment. "Furthermore, as oncology social workers it is our job to help patients understand and play an active role in their treatment decisions. Specifically, I encourage breast cancer patients to ask for PathVysion FISH to ensure that their HER2 status is diagnosed as accurately as possible."
FISH testing continues to gain global awareness as a valuable diagnostic tool for determining HER2 status. The Japanese Ministry of Health, Labour and Welfare announced on April 6th that HER2 testing with FISH had been approved for government reimbursement. In Europe, Abbott is in the process of seeking CE certification. The CE mark indicates that a company has met essential health and safety requirements for a particular product and can market it throughout the European Union.
Abbott's Diagnostics Division is a global leader in in vitro diagnostics and offers a broad range of instrument systems and tests across key segments in the global diagnostics market, including hospitals, reference labs, blood banks, physician offices, clinics and consumers. Through its Vysis subsidiary and its exclusive alliance with Celera Diagnostics, Abbott also offers a broad range of in vitro molecular diagnostic products that provide information critical to the evaluation and management of cancer, prenatal disorders and other genetic diseases.