The debate on how to select patients who will respond best to costly drug treatments for aggressive breast cancer now favors fluorescence in situ hybridization (FISH) to measure the HER-2 receptor found in human breast tumors, according to a leading pathologist presenting at the Association for Molecular Pathology annual meeting.

Michael Press, M.D., Ph.D., pathologist and Harold E. Lee Chair in Cancer Research, Norris Comprehensive Cancer Center, University of Southern California, told a symposium audience that a growing body of research in recent years demonstrates that FISH technology is an accurate, reproducible and predictive diagnostic method for testing women with breast cancer who are candidates for drug treatments targeted to the HER-2 tumor receptor. The drugs are Herceptin® (trastuzumab) and lapatinib. His remarks were presented at a symposium sponsored by Abbott Molecular.

HER-2 is a tumor marker for aggressive disease and to measure response to targeted therapies.

The protein is a molecular target for the two medications, which suppress the HER-2 signal transduction pathway. For patients with HER-2-positive tumors, both drugs are clearly associated with improved clinical outcomes in metastatic breast cancer, and Herceptin is approved for use as adjuvant therapy.

Earlier this year, Press co-authored an article published in the Journal of Clinical Oncology refuting guidelines developed by the American Society of Clinical Oncology and the College of American Pathologists that recommended immunohistochemistry (IHC) as the preferred diagnostic method for determining a breast-cancer patient’s HER-2 status.

“Evaluation of HER-2 status should consider the costs of treatment as well as the potential benefits of therapy,” Press said. “And the cost of the diagnostic test is minimal compared with the cost of the medications. More accurate assignment of patients to treatment more than offsets the costs of erroneously treating women whose breast cancers lack HER-2 amplification.

In addition, there is the human cost of failing to treat women whose breast cancers have HER-2 amplification.”

“An issue with FISH for HER-2 testing is that up to 2 percent of breast cancers have FISH ratios at or near the cutoff level. However, we are aware of no published data demonstrating that patients with borderline HER-2 amplification respond less favorably to trastuzumab and lapatinib,” he said.

Breast Cancer Incidence
According to the World Health Organization, more than1.2 million cases of breast cancer are diagnosed every year and about 75 percent of them are women age 50 and older. It is estimated that 12.6 percent of all women will get breast cancer in their lifetimes, and about 80 percent of those diagnosed with the disease have no family history of breast cancer. The good news is that early detection greatly maximizes survival through breast self exams and mammography.

About FISH
Abbott Molecular’s PathVysion HER-2 DNA Probe Kit is designed to detect amplification of the HER-2/neu gene via fluorescence in situ hybridization (FISH) in formalin-fixed, paraffin-embedded human breast cancer tissue specimens. Results from the PathVysion kit are intended for use as an adjunct to existing clinical and pathologic information currently used as prognostic factors in stage II, node-positive breast cancer patients. The PathVysion kit is further indicated as an aid to predict disease-free and overall survival in patients with stage II, node positive breast cancer treated with adjuvant cyclophosphamide, doxorubicin, and 5-fluorouracil (CAF) chemotherapy. The PathVysion kit is indicated as an aid in the assessment of patients for whom HERCEPTIN® (Trastuzumab) treatment is being considered (see HERCEPTIN package insert). The PathVysion kit is not intended for use to screen for or diagnose breast cancer. It is intended to be used as an adjunct to other prognostic factors currently used to predict disease-free and overall survival in stage II, node-positive breast cancer patients, and no treatment decisions for stage II, node-positive breast cancer patients should be based on HER-2/neu gene amplification status alone. Selected patients with breast cancers shown to lack amplification of HER-2/neu may still benefit from CAF adjuvant therapy on the basis of other prognostic factors which predict poor outcome (e.g. tumor size, number of involved lymph nodes, and hormone receptor status).

Conversely, selected patients with breast cancers shown to contain gene amplification may not be candidates for CAF therapy due to pre-existing or intercurrent medical illnesses.

About Abbott Molecular
Abbott Molecular (abbottmolecular.com) is an emerging leader in molecular diagnostics - the analysis of DNA, RNA, and proteins at the molecular level. Abbott Molecular’s instruments and reagents detect pathogens and subtle, but key changes in patients’ genes and chromosomes, which permit earlier diagnoses, the selection of appropriate therapies and improved monitoring of disease progression.

About Abbott
Abbott is a global, broad-based health care company devoted to the discovery, development, manufacture and marketing of pharmaceuticals and medical products, including nutritionals, devices and diagnostics. The company employs more than 72,000 people and markets its products in more than 130 countries.

Source:  Abbott Molecular