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Feb 3, 2008 09:38AM
Mar 19, 2008 09:39AM
Your situation gives me pause.
It appears that your equivocal results on HER2/neu testing may prompt a second (or third look) at your individual situation, particularly by a clinician expert in HER2 positive disease states.
I can think of two scenerios for discussion:
a) Do equivocal results themselves merit Herceptin treatment under close supervision, due to the known benefits of decrease in recurrence with this monoclonal antibody?
b) Being ER/PR+ with equivocal HER2+ status is Herceptin treatment of merit? This point is driven by data suggesting ER+ status crosstalks with HER, and is best left to discussion with your doctors.
Here then is the ASCO guidelines on HER2 testing, specifically discussing "equivocal" states.
"American Society of Clinical Oncology-College of American Pathologists Guideline Recommendations for Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer
Antonio C. Wolff*, M. Elizabeth H. Hammond*, Jared N. Schwartz*, Karen Hagerty, D. Craig Allred, Richard Cote, Mitchell Dowsett, Patrick L. Fitzgibbons, Steven Gutman, Wedad Hanna, Patricia Keegan, Amy Langer, Lisa M. McShane, Soonmyung Paik, Mark D. Pegram, Edith A. Perez, Michael F. Press, Anthony Rhodes, Catharine Sturgeon, Sheila Taube, Raymond Tubbs, Gail H. Vance, Marc van de Vijver, Thomas Wheeler, Judy Yost, and Daniel F. Hayes*
*ASCO/CAP Expert Panel Co-Chairs
Purpose: To develop a guideline to improve the accuracy of human epidermal growth factor receptor 2 (HER2) testing in invasive breast cancer and its utility as a predictive marker.
Methods: The American Society of Clinical Oncology and the College of American Pathologists convened an expert panel, which conducted a systematic review of the literature and developed recommendations for optimal HER2 testing performance. The guideline was reviewed by selected experts and approved by the board of directors for both organizations.
Results: Approximately 20% of current HER2 testing may be inaccurate. When carefully validated testing is performed, available data do not clearly demonstrate the superiority of either immunohistochemistry (IHC) or in situ hybridization (ISH) as a predictor of benefit from anti-HER2 therapy.
Recommendations: The panel recommends that HER2 status should be determined for all invasive breast cancer. A testing algorithm that relies on accurate, reproducible assay performance, including newly available types of brightfield ISH, is proposed. Elements to reliably reduce assay variation (for example, specimen handling, assay exclusion, and reporting criteria) are specified. An algorithm defining positive, equivocal, and negative values for both HER2 protein expression and gene amplification is recommended: a positive HER2 result is IHC staining of 3+ (uniform, intense membrane staining of > 30% of invasive tumor cells), a fluorescent in situ hybridization (FISH) result of more than six HER2 gene copies per nucleus or a FISH ratio (HER2 gene signals to chromosome 17 signals) of more than 2.2; a negative result is an IHC staining of 0 or 1+, a FISH result of less than 4.0 HER2 gene copies per nucleus, or FISH ratio of less than 1.8. Equivocal results require additional action for final determination. It is recommended that to perform HER2 testing, laboratories show 95% concordance with another validated test for positive and negative assay values. The panel strongly recommends validation of laboratory assay or modifications, use of standardized operating procedures, and compliance with new testing criteria to be monitored with the use of stringent laboratory accreditation standards, proficiency testing, and competency assessment. The panel recommends that HER2 testing be done in a CAP-accredited laboratory or in a laboratory that meets the accreditation and proficiency testing requirements set out by this document."
And here is an eligibility statement of HER in a clinical trial that got me thinking on your situation:
"Patients will be considered to be eligible if HER2 expression is documented by one of the following methods: - IHC, 1+, 2+, or 3+ levels of expression or -Gene amplification [FISH], positive as determined by the laboratory performing the test or - Serum HER2 ECD greater than or equal to 15 ng/ml". (Note, this is just to illustrate a clinical trial example).
Our personal oncologist's carry great knowledge on HER2 disease states. As one can see though, you fall in a gray zone which may benefit from the "two heads" theory of help. Hope this helps.
All the best to you and other HER ladies.
It cannot be emphasized too strongly that treatment of each patient is a highly individualized matter. (FDA-approved labeling for warfarin (Coumadin) NDA 9-218/5-105)