PMID- 25886996 OWN - NLM STAT- MEDLINE DCOM- 20160115 LR - 20181113 IS - 1465-542X (Electronic) IS - 1465-5411 (Print) IS - 1465-5411 (Linking) VI - 17 IP - 1 DP - 2015 Mar 18 TI - Quantitative measurement of HER2 expression in breast cancers: comparison with 'real-world' routine HER2 testing in a multicenter Collaborative Biomarker Study and correlation with overall survival. PG - 41 LID - 10.1186/s13058-015-0543-x [doi] LID - 41 AB - INTRODUCTION: Accurate assessment of HER2 status is critical in determining appropriate therapy for breast cancer patients but the best HER2 testing methodology has yet to be defined. In this study, we compared quantitative HER2 expression by the HERmark Breast Cancer Assay (HERmark) with routine HER2 testing by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), and correlated HER2 results with overall survival (OS) of breast cancer patients in a multicenter Collaborative Biomarker Study (CBS). METHODS: Two hundred and thirty-two formalin-fixed, paraffin-embedded breast cancer tissues and local laboratory HER2 testing results were provided by 11 CBS sites. HERmark assay and central laboratory HER2 IHC retesting were retrospectively performed in a blinded fashion. HER2 results by all testing methods were obtained in 192 cases. RESULTS: HERmark yielded a continuum of total HER2 expression (H2T) ranging from 0.3 to 403 RF/mm2 (approximately 3 logs). The distribution of H2T levels correlated significantly (P<0.0001) with all routine HER2 testing results. The concordance of positive and negative values (equivocal cases excluded) between HERmark and routine HER2 testing was 84% for local IHC, 96% for central IHC, 85% for local FISH, and 84% for local HER2 status. OS analysis revealed a significant correlation of shorter OS with HER2 positivity by local IHC (HR=2.6, P=0.016), central IHC (HR=3.2, P=0.015), and HERmark (HR=5.1, P<0.0001) in this cohort of patients most of whom received no HER2-targeted therapy. The OS curve of discordant low (HER2 positive but H2T low, 10% of all cases) was aligned with concordant negative (HER2 negative and H2T low, HR=1.9, P=0.444), but showed a significantly longer OS than concordant positive (HER2 positive and H2T high, HR=0.31, P=0.024). Conversely, the OS curve of discordant high (HER2 negative but H2T high, 9% of all cases) was aligned with concordant positive (HR=0.41, P=0.105), but showed a significantly shorter OS than concordant negative (HR=41, P<0.0001). CONCLUSIONS: Quantitative HER2 measurement by HERmark is highly sensitive, accurately quantifies HER2 protein expression and correlates well with routine HER2 testing. When HERmark and local HER2 results were discordant, HERmark more accurately predicted overall survival. FAU - Yardley, Denise A AU - Yardley DA AD - Sarah Cannon Research Institute, 3322 West End Avenue, Nashville, TN, 37203, USA. dyardley@tnonc.com. AD - Tennessee Oncology, PLLC, 250 25th Avenue North, Nashville, TN, 37203, USA. dyardley@tnonc.com. FAU - Kaufman, Peter A AU - Kaufman PA AD - Dartmouth Hitchcock Medical Center, 1 Medical Center Drive, Lebanon, NH, 03766, USA. Peter.A.Kaufman@hitchcock.org. FAU - Huang, Weidong AU - Huang W AD - Monogram Biosciences, Inc., 345 Oyster Point Boulevard, South San Francisco, CA, 37203, USA. huangw2@labcorp.com. FAU - Krekow, Lea AU - Krekow L AD - Texas Oncology Bedford, 1615 Hospital Parkway, Bedford, TX, 76022, USA. Lea.krekow@usoncology.com. FAU - Savin, Michael AU - Savin M AD - Texas Oncology and Medical City, 7777 Forest Lane, Dallas, TX, 75230, USA. michael.savin@usoncology.com. FAU - Lawler, William E AU - Lawler WE AD - St. Jude Heritage Medical Group, 2720 Harbor Boulevard, Fullerton, CA, 92835, USA. wlawler@stjoe.org. FAU - Zrada, Stephen AU - Zrada S AD - The Center for Cancer and Hematologic Disease, 1930 New Jersey 70 (East), Cherry Hill, NJ, 08003, USA. ndinubile@centerforcancer.com. FAU - Starr, Alexander AU - Starr A AD - Monroe Medical Associates, 71 Ald Taylor Way, Harvey, IL, 60426, USA. starr.alex@comcast.net. FAU - Einhorn, Harvey AU - Einhorn H AD - Swedish American Regional Medical Center, 1401 East State Street, Rockford, IL, 61104, USA. rkinnear@swedishamerican.org. FAU - Schwartzberg, Lee S AU - Schwartzberg LS AD - The West Clinic, 100 N Humphreys Boulevard, Memphis, TN, 38120, USA. lschwartzberg@westclinic.com. FAU - Adams, John W AU - Adams JW AD - Arlington Cancer Center, 906 West Randol Mill Road, Arlington, TX, 76012, USA. jadams@acc-tx.com. FAU - Lie, Yolanda AU - Lie Y AD - Monogram Biosciences, Inc., 345 Oyster Point Boulevard, South San Francisco, CA, 37203, USA. Liey@labcorp.com. FAU - Paquet, Agnes C AU - Paquet AC AD - Monogram Biosciences, Inc., 345 Oyster Point Boulevard, South San Francisco, CA, 37203, USA. paquet@ipmc.cnrs.fr. AD - Present address: Institut de Pharmacologie Moleculaire et Cellulaire-IPMC, Sophia Antipolis, 660 Route des Lucioles, 06560, Valbonne, France. paquet@ipmc.cnrs.fr. FAU - Sperinde, Jeff AU - Sperinde J AD - Monogram Biosciences, Inc., 345 Oyster Point Boulevard, South San Francisco, CA, 37203, USA. Sperinj@labcorp.com. FAU - Haddad, Mojgan AU - Haddad M AD - Monogram Biosciences, Inc., 345 Oyster Point Boulevard, South San Francisco, CA, 37203, USA. Mojgan.Haddad@HealthTell.com. AD - Present address: HealthTell, 3130 Crow Canyon Place, San Ramon, CA, 94583, USA. Mojgan.Haddad@HealthTell.com. FAU - Anderson, Steve AU - Anderson S AD - Monogram Biosciences, Inc., 345 Oyster Point Boulevard, South San Francisco, CA, 37203, USA. sanderson@LabCorp.com. FAU - Brigino, Marlon AU - Brigino M AD - Center for Molecular Biology and Pathology, Laboratory Corporation of America, Inc, Research Triangle Park, NC, 27709, USA. Briginm@LabCorp.com. FAU - Pesano, Rick AU - Pesano R AD - Monogram Biosciences, Inc., 345 Oyster Point Boulevard, South San Francisco, CA, 37203, USA. Rick.L.Pesano@QuestDiagnostics.com. AD - Present address: Quest Diagnostics, 33608 Ortega Highway, San Juan Capistrano, CA, 92675, USA. Rick.L.Pesano@QuestDiagnostics.com. FAU - Bates, Michael P AU - Bates MP AD - Monogram Biosciences, Inc., 345 Oyster Point Boulevard, South San Francisco, CA, 37203, USA. Michael.Bates@cepheid.com. AD - Present address: Cepheid, 904 East Caribbean Drive, Sunnyvale, CA, 94089, USA. Michael.Bates@cepheid.com. FAU - Weidler, Jodi AU - Weidler J AD - Monogram Biosciences, Inc., 345 Oyster Point Boulevard, South San Francisco, CA, 37203, USA. Jodi.Weidler@cepheid.com. AD - Present address: Cepheid, 904 East Caribbean Drive, Sunnyvale, CA, 94089, USA. Jodi.Weidler@cepheid.com. FAU - Bosserman, Linda AU - Bosserman L AD - Wilshire Oncology Medical Group, 8283 Grove Avenue, Rancho Cucamonga, CA, 91730, USA. lbosserman@coh.org. AD - Present address: City of Hope, 1500 East Duarte Road, Rancho Cucamonga, CA, 91010, USA. lbosserman@coh.org. LA - eng PT - Journal Article PT - Multicenter Study DEP - 20150318 PL - England TA - Breast Cancer Res JT - Breast cancer research : BCR JID - 100927353 RN - 0 (Biomarkers, Tumor) RN - EC 2.7.10.1 (Receptor, ErbB-2) SB - IM MH - Adult MH - Aged MH - Biomarkers, Tumor/genetics/metabolism MH - Breast Neoplasms/diagnosis/*genetics/*metabolism/mortality MH - Female MH - Follow-Up Studies MH - Humans MH - *Immunohistochemistry/methods MH - *In Situ Hybridization, Fluorescence/methods MH - Kaplan-Meier Estimate MH - Middle Aged MH - Neoplasm Grading MH - Neoplasm Staging MH - Prognosis MH - Receptor, ErbB-2/*genetics/*metabolism MH - Reproducibility of Results MH - Retrospective Studies MH - Risk Factors MH - Tumor Burden MH - Young Adult PMC - PMC4391602 EDAT- 2015/04/19 06:00 MHDA- 2016/01/16 06:00 PMCR- 2015/03/18 CRDT- 2015/04/19 06:00 PHST- 2014/10/14 00:00 [received] PHST- 2015/02/27 00:00 [accepted] PHST- 2015/04/19 06:00 [entrez] PHST- 2015/04/19 06:00 [pubmed] PHST- 2016/01/16 06:00 [medline] PHST- 2015/03/18 00:00 [pmc-release] AID - 10.1186/s13058-015-0543-x [pii] AID - 543 [pii] AID - 10.1186/s13058-015-0543-x [doi] PST - epublish SO - Breast Cancer Res. 2015 Mar 18;17(1):41. doi: 10.1186/s13058-015-0543-x.