Quality improvement analysis of HER2 FISH testing in breast cancer in response to the new ASCO/CAP guidelines.

Abstract

Abstract Abstract #3013 Background: The new ASCO/CAP guidelines for HER2 testing in breast cancer redefined the interpretation of HER2 FISH testing result. A new category of equivocal result is defined as FISH ratio of 1.8-2.2. Patients with equivocal results constitute a poorly studied subgroup with uncertain association of test scores to benefit from HER2-directed therapy. Additional quality control and quality assurance recommendations were also detailed in the guideline. As part of our institutional effort for quality improvement of HER2 testing, we reviewed the FISH HER2 testing performed in our institution for the past four years.
 Methods: The FDA-approved PathVision HER2 FISH kit (Abbott Molecular, CA) was used for all FISH testing. The Herceptest ParmDx antibody (Dako Cytomation) and the Neu-Her2/Cerb-2 antibody (Vision Biosystems) were used for all IHC testing. The new ASCO/CAP interpretation criteria were applied to the FISH enumeration results and compared with the IHC results and interpretation. Correlation with clinical decision of trastuzumab therapy and clinical outcome was reviewed.
 Results: A total of 554 samples between 2004 and 2008 were tested for HER2 FISH. According to the new interpretation criteria, 12.8% of the samples had amplified values and 3.8% of the samples had equivocal values. IHC was negative for Her2 for all the samples with equivocal FISH results. Only one patient was treated with trastuzumab. In addition to this equivocal category, some samples showed genetic heterogeneity with some of the tumor showing cells with HER2 amplification whereas cells at different areas of the same tumor were not amplified. Half of these patients were treated and the remaining 50% were not. The discordant rate between FISH and IHC was 3.6% overall, and aneusomy 17 may explain some of the discordance. Of patients with discordant HER2 results by FISH and IHC, physicians' decision to treat with trastuzumab or not appeared to be based on either FISH or IHC with equal frequencies.
 Conclusion: Due to small sample size and retrospective nature of this review, outcome data was uninformative in these small cohorts. As suggested by the ASCO/CAP expert panel, pooling data from all adjuvant trastuzumab trails on subjects with equivocal results would be helpful to provide an evidence base for physicians to make treatment decisions. Alternatively, we are beginning to explore molecular expression profiles to see whether some of these equivocal or discordant cases behave more like HER2 positive or negative patients. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3013.