Immunohistochemistry and fluorescence in situ hybridization assessment of HER2 in clinical trials of adjuvant therapy fo
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PRECLINICAL STUDY
Immunohistochemistry and fluorescence in situ hybridization assessment of HER2 in clinical trials of adjuvant therapy for breast cancer (NCCTG N9831, BCIRG 006, and BCIRG 005) Edith A. Perez • Michael F. Press • Amylou C. Dueck • Robert B. Jenkins Chungyeul Kim • Beiyun Chen • Ivonne Villalobos • Soonmyung Paik • Marc Buyse • Anne E. Wiktor • Reid Meyer • Melanie Finnigan • JoAnne Zujewski • Mona Shing • Howard M. Stern • Wilma L. Lingle • Monica M. Reinholz • Dennis J. Slamon
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Received: 24 January 2013 / Accepted: 31 January 2013 / Published online: 19 February 2013 Ó The Author(s) 2013. This article is published with open access at Springerlink.com
Abstract A comprehensive, blinded, pathology evaluation of HER2 testing in HER2-positive/negative breast cancers was performed among three central laboratories. Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) analyses were performed on 389 tumor blocks from three large adjuvant trials: N9831, BCIRG-006, and BCIRG-005. In 123 cases, multiple blocks were examined. HER2 status was defined according to FDA-approved guidelines and was independently re-assessed at each site. Discordant cases were adjudicated at an on-site, face-to-face meeting. Results across three independent pathologists were concordant by IHC in 351/381 (92 %) and FISH in 343/373 (92 %) blocks. Upon adjudication, consensus was reached
Electronic supplementary material The online version of this article (doi:10.1007/s10549-013-2444-y) contains supplementary material, which is available to authorized users. E. A. Perez (&) Mayo Clinic, 4500 San Pablo Road S., Jacksonville, FL 32224, USA e-mail: [email protected] M. F. Press I. Villalobos Norris Comprehensive Cancer Center, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA 90033, USA A. C. Dueck Mayo Clinic, 13400 E. Shea Blvd., Scottsdale, AZ 85259, USA R. B. Jenkins B. Chen A. E. Wiktor R. Meyer W. L. Lingle M. M. Reinholz Mayo Clinic, 200 First St. SW, Rochester, MN 55905, USA
on 16/30 and 18/30 of discordant IHC and FISH cases, respectively, resulting in overall concordance rates of 96 and 97 %. Among 155 HER2-negative blocks, HER2 status was confirmed in 153 (99 %). In the subset of 102 HER2-positive patients from N9831/BCIRG-006, primary blocks from discordant cases were selected, especially those with discordant test between local and central laboratories. HER2 status was confirmed in 73 (72 %) of these cases. Among 118 and 113 cases with IHC and FISH results and[1 block evaluable, block-to-block variability/heterogeneity in HER2 results was seen in 10 and 5 %, respectively. IHC-/FISHwas confirmed for 57/59 (97 %) primary blocks from N9831 (locally positive, but centrally negative); however, 5/22 (23 %) secondary blocks showed HER2 positivity. Among 53 N9831 patients with HER2-normal disease adjudicated as IHC-/FISH—(although locally positive), there was a nonstatistically significant improvement in disease-free survival M. Buyse IDDI, Belgium, Avenue Provinciale, 30
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