This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dressler, L. G. Articles by Hayes, D. F. Search for Related Content PubMed PubMed Citation Articles by Dressler, L. G. Articles by Hayes, D. F. Social Bookmarking                            What's this?

Comparison of HER2 Status by Fluorescence in Situ Hybridization and Immunohistochemistry to Predict Benefit From Dose Escalation of Adjuvant Doxorubicin-Based Therapy in Node-Positive Breast Cancer Patients

From the Lineberger Comprehensive Cancer Center; Department of Medicine; Department of Pathology, University of North Carolina at Chapel Hill, Chapel Hill, NC; The University of Texas M.D. Anderson Cancer Center, Houston, TX; Cancer and Leukemia Group B (CALGB) Statistical Center, Duke University School of Medicine, Durham, NC; University of Kansas Medical Center, Kansas City, KS; Department of Pathology, Roswell Park Cancer Institute, Buffalo, NY; University of California at San Francisco, San Francisco, CA; Genome Institute of Singapore, Singapore; Department of Pathology, University of Oklahoma, Oklahoma City, OK; North Shore Long Island Jewish Health System, Manhasset, NY; University of Vermont, Burlington, VT; Memorial Sloan-Kettering Cancer Center, New York, NY; and University of Michigan, Ann Arbor, MI

Address reprint requests to Lynn G. Dressler, DrPH, University of North Carolina, Lineberger Comprehensive Cancer Center, CB 7295, Mason Farm Rd, Chapel Hill, NC 27599-7295, e-mail: dressler{at}med.unc.edu

PURPOSE: HER2 is a clinically important tumor marker in breast cancer; however, there is controversy regarding which method reliably measures HER2 status. We compared three HER2 laboratory methods: immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR), to predict disease-free survival (DFS) and overall survival (OS) after adjuvant doxorubicin-based therapy in node-positive breast cancer patients.

METHODS: This is a Cancer and Leukemia Group B (CALGB) study, using 524 tumor blocks collected from breast cancer patients registered to clinical trial CALGB 8541. IHC employed CB11 and AO-11-854 monoclonal antibodies; FISH used PathVysion HER2 DNA Probe kit; PCR utilized differential PCR (D-PCR) methodology.

RESULTS: Cases HER2 positive by IHC, FISH and D-PCR were 24%, 17%, and 18%, respectively. FISH and IHC were clearly related ( = 64.8%). All three methods demonstrated a similar relationship for DFS and OS. By any method, for patients with HER2-negative tumors, there was little or no effect of dose of adjuvant doxorubicin-based therapy. For patients with HER2-positive tumors, all three methods predicted a benefit from dose-intense (high-dose) compared with low- or moderate-dose adjuvant doxorubicin-based therapy.

CONCLUSION: FISH is a reliable method to predict clinical outcome following adjuvant doxorubicin-based therapy for stage II breast cancer patients. There is a moderate level of concordance among the three methods (IHC, FISH, PCR). None of the methods is clearly superior. Although IHC-positive/FISH-positive tumors yielded the greatest interaction with dose of therapy in predicting outcome, no combination of assays tested was statistically superior.

Supported in part by grants from the National Cancer Institute (National Institutes of Health, Bethesda, MD; CA31946) to the Cancer and Leukemia Group B (Richard L. Schilsky, MD, Chairman) and by NCI-U01-CA64061-05, the T.J. Martell Foundation for Leukemia, Cancer and AIDS Research, and Vysis Inc, Downers Grove, IL.

The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				L. N. Harris, G. Broadwater, M. Abu-Khalaf, D. Cowan, A. D. Thor, D. Budman, C. T. Cirrincione, D. A. Berry, E. P. Winer, C. A. Hudis, et al. Topoisomerase II{alpha} Amplification Does Not Predict Benefit From Dose-Intense Cyclophosphamide, Doxorubicin, and Fluorouracil Therapy in HER2-Amplified Early Breast Cancer: Results of CALGB 8541/150013 J. Clin. Oncol., July 20, 2009; 27(21): 3430 - 3436. [Abstract] [Full Text] [PDF]

				J Zustin, K Boddin, M C Tsourlakis, E Burandt, M Mirlacher, F Jaenicke, J Izbicki, W Ruether, J M Rueger, C Bokemeyer, et al. HER-2/neu analysis in breast cancer bone metastases J. Clin. Pathol., June 1, 2009; 62(6): 542 - 546. [Abstract] [Full Text] [PDF]

				D. J. Slamon and M. F. Press Alterations in the TOP2A and HER2 Genes: Association With Adjuvant Anthracycline Sensitivity in Human Breast Cancers J Natl Cancer Inst, May 6, 2009; 101(9): 615 - 618. [Full Text] [PDF]

				E. de Azambuja, M. Paesmans, M. Beauduin, A. Vindevoghel, N. Cornez, C. Finet, F. Ries, M. T. Closon-Dejardin, J. Kerger, P. Gobert, et al. Long-Term Benefit of High-Dose Epirubicin in Adjuvant Chemotherapy for Node-Positive Breast Cancer: 15-Year Efficacy Results of the Belgian Multicentre Study J. Clin. Oncol., February 10, 2009; 27(5): 720 - 725. [Abstract] [Full Text] [PDF]

				M. Dowsett and A. K. Dunbier Emerging Biomarkers and New Understanding of Traditional Markers in Personalized Therapy for Breast Cancer Clin. Cancer Res., December 15, 2008; 14(24): 8019 - 8026. [Abstract] [Full Text] [PDF]

				M. P. DiGiovanna, D. F. Stern, S. Edgerton, G. Broadwater, L. G. Dressler, D. R. Budman, I. C. Henderson, L. Norton, E. T. Liu, H. B. Muss, et al. Influence of Activation State of ErbB-2 (HER-2) on Response to Adjuvant Cyclophosphamide, Doxorubicin, and Fluorouracil for Stage II, Node-Positive Breast Cancer: Study 8541 From the Cancer and Leukemia Group B J. Clin. Oncol., May 10, 2008; 26(14): 2364 - 2372. [Abstract] [Full Text] [PDF]

				L.-P. P. Tran and J. L. Grabinski Chemotherapy for Early-Stage Breast Cancer: A Paradigm in Flux Journal of Pharmacy Practice, February 1, 2008; 21(1): 46 - 56. [Abstract] [PDF]

				D. F. Hayes, A. D. Thor, L. G. Dressler, D. Weaver, S. Edgerton, D. Cowan, G. Broadwater, L. J. Goldstein, S. Martino, J. N. Ingle, et al. HER2 and Response to Paclitaxel in Node-Positive Breast Cancer N. Engl. J. Med., October 11, 2007; 357(15): 1496 - 1506. [Abstract] [Full Text] [PDF]

				P. L. Porter, W. E. Barlow, I-T. Yeh, M. G. Lin, X. P. Yuan, E. Donato, G. W. Sledge, C. L. Shapiro, J. N. Ingle, C. M. Haskell, et al. p27Kip1 and Cyclin E Expression and Breast Cancer Survival After Treatment With Adjuvant Chemotherapy J Natl Cancer Inst, December 6, 2006; 98(23): 1723 - 1731. [Abstract] [Full Text] [PDF]

				C. Compton The cancer and leukemia group B pathology committee at 50. Clin. Cancer Res., June 1, 2006; 12(11): 3617s - 3621s. [Abstract] [Full Text] [PDF]

				N. L. Henry and D. F. Hayes Uses and abuses of tumor markers in the diagnosis, monitoring, and treatment of primary and metastatic breast cancer. Oncologist, June 1, 2006; 11(6): 541 - 552. [Abstract] [Full Text] [PDF]

				K. I. Pritchard, L. E. Shepherd, F. P. O'Malley, I. L. Andrulis, D. Tu, V. H. Bramwell, M. N. Levine, and the National Cancer Institute of Canada Clinical T HER2 and Responsiveness of Breast Cancer to Adjuvant Chemotherapy N. Engl. J. Med., May 18, 2006; 354(20): 2103 - 2111. [Abstract] [Full Text] [PDF]

				M. J. Piccart-Gebhart Anthracyclines and the Tailoring of Treatment for Early Breast Cancer N. Engl. J. Med., May 18, 2006; 354(20): 2177 - 2179. [Full Text] [PDF]