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J Clin Oncol. 2016 Oct 10;34(29):3518-3528. doi: 10.1200/JCO.2016.66.6693.

HER2 Gene Amplification Testing by Fluorescent In Situ Hybridization (FISH): Comparison of the ASCO-College of American Pathologists Guidelines With FISH Scores Used for Enrollment in Breast Cancer International Research Group Clinical Trials.

Author information

1
Michael F. Press, Denice D. Tsao-Wei, Yanling Ma, Ivonne Villalobos, and Anaamika Campeau, University of Southern California Norris Comprehensive Cancer Center; Dennis J. Slamon, Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA; Nicholas Robert, Virginia Cancer Specialists/US Oncology Research Network, Fairfax, VA; Vicente Valero, The University of Texas MD Anderson Cancer Center, Houston, TX; Guido Sauter and Martina Mirlacher, University of Hamburg, Hamburg; Wolfgang Eiermann, Frauenklinik vom Roten Kreuz, Munich, Germany; Marc Buyse, Hélène Fourmanoir, and Emmanuel Quinaux, International Drug Development Institute, Louvain-la-Neuve, Belgium; Tadeusz Pienkowski, Postgraduate Medical Education Center, Warsaw, Poland; John Crown, Irish Cooperative Onoclogy Research Group, St Vincent's University Hospital, Dublin, Ireland; Miguel Martin, Instituto de Investigación Sanitaria Gregorio Marañón, Universidad Complutense, Madrid, Spain; John R. Mackey, University of Alberta; Mary-Ann Lindsay, Cancer International Research Group/Translational Research in Oncology, Edmonton, Alberta, Canada; and Valerie Bee, Cancer International Research Group/Translational Research in Oncology, Paris, France.

Abstract

Purpose ASCO and the College of American Pathologists (ASCO-CAP) recently recommended further changes to the evaluation of human epidermal growth factor receptor 2 gene (HER2) amplification by fluorescent in situ hybridization (FISH). We retrospectively assessed the impact of these new guidelines by using annotated Breast Cancer International Research Group (BCIRG) -005, BCIRG-006, and BCIRG-007 clinical trials data for which we have detailed outcomes. Patients and Methods The HER2 FISH status of BCIRG-005/006/007 patients with breast cancers was re-evaluated according to current ASCO-CAP guidelines, which designates five different groups according to HER2 FISH ratio and average HER2 gene copy number per tumor cell: group 1 (in situ hybridization [ISH]-positive): HER2-to-chromosome 17 centromere ratio ≥ 2.0, average HER2 copies ≥ 4.0; group 2 (ISH-positive): ratio ≥ 2.0, copies < 4.0; group 3 (ISH-positive): ratio < 2.0, copies ≥ 6.0; group 4 (ISH-equivocal): ratio < 2.0, copies ≥ 4.0 and < 6.0; and group 5 (ISH-negative): ratio < 2.0, copies < 4.0. We assessed correlations with HER2 protein, clinical outcomes by disease-free survival (DFS) and overall survival (OS) and benefit from trastuzumab therapy (hazard ratio [HR]). Results Among 10,468 patients with breast cancers who were successfully screened for trial entry, 40.8% were in ASCO-CAP ISH group 1, 0.7% in group 2; 0.5% in group 3, 4.1% in group 4, and 53.9% in group 5. Distributions were similar in screened compared with accrued subpopulations. Among accrued patients, FISH group 1 breast cancers were strongly correlated with immunohistochemistry 3+ status (P < .0001), whereas groups 2, 3, 4, and 5 were not; however, groups 2, 4 and, 5 were strongly correlated with immunohistochemistry 0/1+ status (all P < .0001), whereas group 3 was not. Among patients accrued to BCIRG-005, group 4 was not associated with significantly worse DFS or OS compared with group 5. Among patients accrued to BCIRG-006, only group 1 showed a significant benefit from trastuzumab therapy (DFS HR, 0.71; 95% CI, 0.60 to 0.83; P < .0001; OS HR, 0.69; 95% CI, 0.55 to 0.85; P = .0006), whereas group 2 did not. Conclusion Our findings support the original categorizations of HER2 by FISH status in BCIRG/Translational Research in Oncology trials.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00021255 NCT00312208.

PMID:
27573653
PMCID:
PMC5074347
DOI:
10.1200/JCO.2016.66.6693
[Indexed for MEDLINE]
Free PMC Article

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