© 2002 by Oxford University Press
Journal of the National Cancer Institute, Vol. 94, No. 11, 855-857,
June 5, 2002
© 2002 Oxford University Press
BRIEF COMMUNICATION |
Concordance Between Local and Central Laboratory HER2 Testing in the Breast Intergroup Trial N9831
Affiliations of authors: P. C. Roche, V. J. Suman, R. B. Jenkins, J. N. Ingle, Mayo Clinic and Mayo Foundation, Rochester, MN; N. E. Davidson, Eastern Cooperative Oncology Group Data Management Office, Brookline, MA; S. Martino, Southwest Oncology Group Operations Office, San Antonio, TX; P. A. Kaufman, Cancer and Leukemia Group B Data Management Center, Durham, NC; F. K. Addo, Medcenter One Health Systems, and Mid Dakota Clinic, Bismarck, ND; B. Murphy, Metro-Minnesota Community Oncology Program, St. Louis Park, MN; E. A. Perez, Mayo Clinic and Mayo Foundation, Jacksonville, FL.
Correspondence to: Edith A. Perez, M.D., Mayo Clinic, Division of Hematology/Oncology, 4500 San Pablo Rd., Jacksonville, FL 32224 (e-mail: perez.edith{at}mayo.edu).
ABSTRACT
The efficacy of trastuzumab for metastases coupled with the relatively poor prognosis of patients with node-positive, HER2-positive breast cancer has led to the evaluation of trastuzumab as an adjuvant therapy. A prospective, randomized, three-arm, phase III trial is being conducted by the Breast Intergroup (N9831) for women with primary, operable, histologically confirmed, node-positive breast carcinoma that strongly overexpresses (3+) HER2 protein and/or displays HER2/neu gene amplification, as determined by local laboratory testing. The protocol requires confirmatory central testing of HER2 status using the HercepTestTM immunohistochemistry and the Vysis PathVysionTM fluorescence in situ hybridization (FISH) assays. Tumor specimens from the first 119 patients enrolled in N9831 were centrally tested; 74% were found to be HercepTestTM 3+ and 66% were found to have HER2 gene amplification. Only six of nine (67%) of the specimens submitted by local laboratories as FISH positive could be confirmed by central assays. The concordance for central HercepTestTM and central FISH assays was 92%. The poor concordance (74%) between local and central testing for HER2 status has led to modifications in the eligibility criteria for N9831.
Trastuzumab (anti-HER2 therapy, Herceptin), a new targeted antineoplastic agent, is a monoclonal antibody specifically directed against the extracellular domain of the HER2 protein. Treatment with trastuzumab improves outcomes for women with HER2-overexpressing metastatic breast cancer when used in combination with chemotherapy (1) or when used in sequence after chemotherapy (2). Prospective clinical trials evaluating trastuzumab as an adjuvant therapy were designed on the basis of both the efficacy of trastuzumab for patients with metastases and the relatively poor prognosis of patients with axillary lymph node-positive, HER2/neu-positive breast cancer.
One of four ongoing large-scale trials evaluating adjuvant trastuzumab is N9831, a prospective, randomized, three-arm, phase III trial conducted by all members of the Breast Intergroup (Cancer and Leukemia Group B, Eastern Cooperative Oncology Group, Southwest Oncology Group, and North Central Cancer Treatment Group [NCCTG]), with the NCCTG as the coordinating center (trial N9831; http://www.cancer.gov/clinical_trials/finding/) (3). Women with primary operable, histologically confirmed, node-positive breast adenocarcinoma that strongly overexpresses HER2 protein or displays HER2/neu gene amplification in local laboratories are eligible for the trial. Measurement of HER2 protein may be performed by the Food and Drug Administration (FDA)-approved DAKO HercepTestTM (package insert 2001; DAKO, Carpinteria, CA) (3+ score) or another immunohistochemical assay where one third or more invasive tumor cells stain positive (3+) with an anti-HER2 antibody. Gene amplification assays using fluorescence in situ hybridization (FISH) may be performed by PathVysionTM (package insert 2001; Vysis, Inc., Downers Grove, IL) (
2.0 HER2/neu probe/control probe ratio considered amplified) or INFORM (package insert 2001; Ventana Medical Systems, Inc., Tucson, AZ) (5 gene copies of HER2/neu considered amplified). Women whose tumors stain 0–2+ by local community-based immunohistochemistry (IHC) but demonstrate amplification by local community-based FISH are eligible for the study. A schematic showing the randomization and treatment regimen can be found at the Journal's Web site (supplemental Fig. 1, http://jncicancerspectrum.oupjournals.org/jnci/content/vol94/issue11/index.shtml). A secondary endpoint of N9831 is to assess the concordance between HER2 protein overexpression and HER2/neu gene amplification as determined by HercepTestTM and FISH (using PathVysionTM), respectively, at a central testing facility.
We report the results of a planned analysis of the first 119 tumor specimens that underwent central HER2 testing, which assesses the level of agreement between local community HER2 testing and central HER2 testing and the concordance between central HER2 HercepTestTM and central HER2/neu FISH results. The N9831 protocol indicated that if a discrepancy of more than 20% was observed between local and central testing for HER2 status in this analysis, then consideration would be given to changing the provision that patient eligibility be based solely on local HER2 results.
Sections from 119 paraffin-embedded breast tumor specimens were analyzed for HER2 overexpression using the HercepTestTM and a DAKO Autostainer in strict accordance with the manufacturer's instructions in the Immunohistochemistry Laboratory (P. C. Roche, Mayo Clinic, Rochester, MN). The stained slides were interpreted and scored on a 0–3+ scale according to the FDA-approved guidelines for HercepTestTM by the study pathologist. FISH (protocol available at the Journal's Web site [supplemental protocol http://jncicancerspectrum.oupjournals.org/jnci/content/vol94/issue11/index.shtml]), is performed with the PathVysionTM HER2/neu DNA probe kit following the manufacturer's instructions in the Cytogenetics Laboratory (R. B. Jenkins, Mayo Clinic, Rochester, MN). An area of the invasive carcinoma is identified from a hematoxylin-and-eosin-stained serial section from each specimen and outlined on the test slide. Two technologists independently count and analyze the number of fluorescent signals in each of 30 tumor cell nuclei as described (4).
As of July 15, 2001, the specimens of 119 women enrolled on N9831 have been centrally evaluated for HER2 status (Table 1
). HER2 status at enrollment was determined in one of 65 different local U.S. laboratories by the HercepTestTM (50%), other IHC methods (42%), Vysis FISH (7%), or Ventana FISH (1%). Only two of these 65 local laboratories were used by more than 5% of the women.
|
Central testing for HER2 status showed that 88 or 74% (95% confidence interval [CI] = 65% to 82%) of the 119 women had tumor specimens with positive (3+) HER2 protein overexpression and/or HER2/neu gene amplification (Table 1
, A). Central testing also showed that 79 or 66% (95% CI = 57% to 75%) of 119 women had tumor specimens with HER2/neu gene amplification (Table 1, B). Forty-four of the 59 (75%) 3+ specimens by local laboratories using HercepTestTM were found to be 3+ by central testing (Table 1, A). This group of 59 is a subgroup of the 110 specimens tested by IHC in the local laboratories. Of the nine tumors reported to have HER2/neu gene amplification by local testing, six (67%) were found to have HER2/neu gene amplification by central testing (Table 1, B). The results of central testing for HER2 are considered to be concordant if the central HercepTestTM score is 0, 1+, or 2+ and the HER2/neu gene is not amplified by central FISH testing or the central HercepTestTM score is 3+ and the HER2/neu gene is amplified by central FISH testing. The degree of concordance for central evaluation between IHC and FISH of the 119 specimens was 92% (Table 2). The discordance occurred among nine (8%) specimens classified as HER2/neu not amplified by FISH but as 3+ by HercepTestTM.
|
Our results demonstrate that there is poor agreement between the results from local laboratory-based HER2 testing and those of central testing by experienced investigators. Some factors that may contribute to these discrepancies could include deviation from standardized testing protocols, inexperience with scoring IHC staining patterns, interpretation made on the basis of the in situ cancer rather than the invasive cancer component, and difficulty in evaluating tumors with chromosome 17 polysomy.
The poor concordance (74%) between local laboratory results of HER2 positivity and central laboratory findings using HercepTestTM or FISH is of great concern because the benefit of trastuzumab, at least in retrospective studies, appears to be observed primarily in patients whose tumors overexpress HER2 protein by IHC or gene amplification by FISH (5–7). So far, our results indicate that as many as 26% of the patients already enrolled using local testing for entry criteria may not be the best candidates to determine whether anti-HER2 monoclonal antibody therapy is advantageous as an adjuvant for chemotherapy. We did not address whether the volume of HER2 tests performed by local laboratories influenced the concordance with our central testing or whether a particular testing method may be contributing to the discordance. Only two of 65 laboratories were used by more than 5% of the women. Thus, our data do not allow us to conclude whether testing only in other reference laboratories or changes in methodology would eliminate the problem of discordance.
We have chosen to modify the HER2 testing requirement for our N9831 clinical trial 1) to ensure the enrollment of patients with the highest probability of benefiting from anti-HER2 monoclonal antibody therapy [such patients would be the most appropriate population to address the primary aim of this clinical trial (trial N9831; http://www.cancer.gov/clinical_trials/finding/) (3)], and 2) to ensure the protection of patients who do not strongly overexpress HER2 from the experimental aspects of treatment with trastuzumab. A notification regarding discordant findings of HER2 testing has been sent to physicians and patients already participating in this clinical trial. Protocol eligibility was modified so that a woman can enroll onto the trial if she has node-positive breast cancer that is found to strongly overexpress HER2 or has HER2/neu gene amplification by central testing or by a local laboratory. If the woman was enrolled on the basis of local laboratory testing, then central confirmatory testing will be performed before the completion of the first chemotherapy regimen. After central review, if the tumor specimen is found to strongly overexpress HER2 (3+ positivity by HercepTestTM) or has HER2/neu amplification by FISH, then the patient will continue protocol treatment as randomly assigned. However, if the tumor specimen does not meet the central testing criteria, the specimen will be sent to an additional reference laboratory for review and, if the testing is still negative, then the patient and her physician will be informed of the findings, and adjuvant therapy will be continued at the individual physician's discretion.
In summary, the overall performance of HER2 testing by local laboratories in this initial sample of 119 patients was disappointing, with unacceptably high levels of discordance with central testing. Although most of our experience involved IHC, finding three discordant cases of nine tested by FISH indicates the need for further evaluation of this assay as used by local oncology and pathology practices. Specific guidelines to gain proficiency in HER2 testing are difficult to specify, but there is general agreement that this is related to the volume of testing and rigorous quality-control measures, including correlative studies involving both IHC and FISH. Based on the findings with this initial sample and the critical importance of accurate HER2 testing for optimal patient care, we conclude that further study of the inter-laboratory agreement is indicated.
NOTES
Note added in proof: Specimens from 370 women were centrally tested as of February 21, 2002. The results are nearly identical to those presented in this report for 119 women. Seventy-five percent (279/370) of enrolled women had tumors that are 3+ by central IHC, and 71% (263/370) had tumors that are amplified by central FISH. Of 36 women (10%) enrolled with local FISH testing, 23 (64%) had tumors that are amplified by central FISH and 26 (72%) had tumors that are 3+ by central IHC. The concordance for central IHC and central FISH is 92% (342/370).
R. B. Jenkins serves on the Scientific Advisory Board of Vysis, Inc., and conducts research sponsored by the company.
P. A. Kaufman conducts research sponsored by Genentech, and is a member of the Genentech Speaker's Bureau.
E. A. Perez conducts research sponsored by Genentech.
Genentech is providing a research grant to partially cover the data analysis (including HER2 testing and cardiac testing) in this trial.
This study was conducted as a collaborative trial of the North Central Cancer Treatment Group and Mayo Clinic and was supported in part by Public Health Service grants CA25224, CA37404, CA15083, CA63826, CA52352, CA63849, CA35195, CA35272, CA60276, CA35269, CA37417, CA63848, CA35101, CA35415, CA35103, and U10CA25224–21 from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services. Other support for this study was provided by grants from the Breast Cancer Research Foundation and Genentech.
REFERENCES
1
Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 2001;344:783–92.
2
Cobleigh MA, Vogel CL, Tripathy D, Robert NJ, Scholl S, Fehrenbacher L, et al. Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J Clin Oncol 1999;17:2639–48.
3 Perez EA, Comis RL, Kaufman PA, Martino S. Phase III randomized study of doxorubicin plus cyclophosphamide followed by paclitaxel with or without trastuzumab (Herceptin) in patients with HER-2-overexpressing breast cancer. [Accessed 04/30/02.] Available from: http://www.cancer.gov/clinical_trials/finding/.
4
Perez EA, Roche PC, Jenkins RB, Reynolds CA, Halling KC, Ingle JN, et al. HER2 testing in patients with breast cancer: poor correlation between weak positivity by immunohistochemistry and gene amplification by fluorescence in situ hybridization. Mayo Clin Proc 2002;77:148–54.
5 Mass RD, Sanders C, Charlene K, Johnson L, Everett T, Anderson S. The concordance between the clinical trials assay (CTA) and fluorescence in situ hybridization (FISH) in the Herceptin pivotal trials [abstract 291]. Proc ASCO 2000;19:75a.
6 Mass RD, Press M, Anderson S, Murphy M, Slamon D. Improved survival benefit from Herceptin (trastuzumab) in patients selected by fluorescence in situ hybridization (FISH) [abstract 85]. Proc ASCO 2001;20:22a.
7 Vogel CL, Cobleigh M, Tripathy D, Mass R, Murphy M, Stewart SJ, et al. Superior outcomes with Herceptin (trastuzumab) (H) in fluorescence in situ hybridization (FISH)-selected patients [abstract 86]. Proc ASCO 2001;20:22a.
Manuscript received November 29, 2001; revised April 2, 2002; accepted April 23, 2002.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  G. Sauter, J. Lee, D. J. Slamon, and M. F. Press Reply to E.H. Hammond et al J. Clin. Oncol., October 20, 2009; 27(30): e155 - e157. [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. Barron, M. J. Cziraky, T. Weisman, and D. G. Hicks HER2 Testing and Subsequent Trastuzumab Treatment for Breast Cancer in a Managed Care Environment Oncologist, August 1, 2009; 14(8): 760 - 768. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Bueno-de-Mesquita, D. S. A. Nuyten, J. Wesseling, H. van Tinteren, S. C. Linn, and M. J. van de Vijver The impact of inter-observer variation in pathological assessment of node-negative breast cancer on clinical risk assessment and patient selection for adjuvant systemic treatment Ann. Onc., July 21, 2009; (2009) mdp273v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Minot, B. R. Kipp, R. M. Root, R. G. Meyer, C. A. Reynolds, A. Nassar, M. R. Henry, and A. C. Clayton Automated Cellular Imaging System III for Assessing HER2 Status in Breast Cancer Specimens: Development of a Standardized Scoring Method That Correlates With FISH Am J Clin Pathol, July 1, 2009; 132(1): 133 - 138. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Sauter, J. Lee, J. M.S. Bartlett, D. J. Slamon, and M. F. Press Reply to V. Arena et al J. Clin. Oncol., July 1, 2009; 27(19): e9 - e10. [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Xiao, X. Gao, S. Maragh, W. G. Telford, and A. Tona Cell Lines as Candidate Reference Materials for Quality Control of ERBB2 Amplification and Expression Assays in Breast Cancer Clin. Chem., July 1, 2009; 55(7): 1307 - 1315. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Plebani, G. Lippi, J. M.S. Bartlett, K. Miller, D. G. Hicks, and S. Kulkarni HER2: Closing the Gap Between Laboratory Testing and Clinical Practice Am J Clin Pathol, June 1, 2009; 131(6): 897 - 898. [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Onitilo, J. M. Engel, R. T. Greenlee, and B. N. Mukesh Breast Cancer Subtypes Based on ER/PR and Her2 Expression: Comparison of Clinicopathologic Features and Survival Clin. Med. Res., June 1, 2009; 7(1-2): 4 - 13. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Brunelli, E. Manfrin, G. Martignoni, K. Miller, A. Remo, D. Reghellin, S. Bersani, S. Gobbo, A. Eccher, M. Chilosi, et al. Genotypic Intratumoral Heterogeneity in Breast Carcinoma With HER2/neu Amplification: Evaluation According to ASCO/CAP Criteria Am J Clin Pathol, May 1, 2009; 131(5): 678 - 682. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Gong, W. Sweet, Y.-J. Duh, L. Greenfield, Y. Fang, J. Zhao, E. Tarco, W. F. Symmans, J. Isola, and N. Sneige Chromogenic In Situ Hybridization Is a Reliable Method for Detecting HER2 Gene Status in Breast Cancer: A Multicenter Study Using Conventional Scoring Criteria and the New ASCO/CAP Recommendations Am J Clin Pathol, April 1, 2009; 131(4): 490 - 497. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. F. Leary, W. M. Hanna, M. J. van de Vijver, F. Penault-Llorca, J. Ruschoff, R. Y. Osamura, M. Bilous, and M. Dowsett Value and Limitations of Measuring HER-2 Extracellular Domain in the Serum of Breast Cancer Patients J. Clin. Oncol., April 1, 2009; 27(10): 1694 - 1705. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Sauter, J. Lee, J. M.S. Bartlett, D. J. Slamon, and M. F. Press Guidelines for Human Epidermal Growth Factor Receptor 2 Testing: Biologic and Methodologic Considerations J. Clin. Oncol., March 10, 2009; 27(8): 1323 - 1333. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. F. Press, R. S. Finn, D. Cameron, A. Di Leo, C. E. Geyer, I. E. Villalobos, A. Santiago, R. Guzman, A. Gasparyan, Y. Ma, et al. HER-2 Gene Amplification, HER-2 and Epidermal Growth Factor Receptor mRNA and Protein Expression, and Lapatinib Efficacy in Women with Metastatic Breast Cancer Clin. Cancer Res., December 1, 2008; 14(23): 7861 - 7870. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Carbone, G. Botti, A. Gloghini, G. Simone, M. Truini, M. P. Curcio, P. Gasparini, A. Mangia, T. Perin, S. Salvi, et al. Delineation of HER2 Gene Status in Breast Carcinoma by Silver in Situ Hybridization is Reproducible among Laboratories and Pathologists J. Mol. Diagn., November 1, 2008; 10(6): 527 - 536. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Vanden Bempt, P. Van Loo, M. Drijkoningen, P. Neven, A. Smeets, M.-R. Christiaens, R. Paridaens, and C. De Wolf-Peeters Polysomy 17 in Breast Cancer: Clinicopathologic Significance and Impact on HER-2 Testing J. Clin. Oncol., October 20, 2008; 26(30): 4869 - 4874. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. L. Gomez, D. C. Doval, M. A. Chavez, P. C.-S. Ang, Z. Aziz, S. Nag, C. Ng, S. X. Franco, L. W.C. Chow, M. C. Arbushites, et al. Efficacy and Safety of Lapatinib As First-Line Therapy for ErbB2-Amplified Locally Advanced or Metastatic Breast Cancer J. Clin. Oncol., June 20, 2008; 26(18): 2999 - 3005. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. K.T. Tan, L. K. Tan, K. Yu, P. H. Tan, M. Lee, L. H. Sii, C. Y. Wong, G. H. Ho, A. W.Y. Yeo, P. K.H. Chow, et al. Clinical Validation of a Customized Multiple Signature Microarray for Breast Cancer Clin. Cancer Res., January 15, 2008; 14(2): 461 - 469. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. C. Wolff, S. Paik, and M. F. Press HER2 as a Predictive Marker: Why Bother Testing? ASCO Educational Book, January 1, 2008; 2008(1): 25 - 28. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. P. Carden, D. Olmos, and J. S. de Bono Validated and Qualified Biomarkers Are Critical to Optimizing Anticancer Drug Development: Potential Roles for the Study of Circulating Tumor Cells ASCO Educational Book, January 1, 2008; 2008(1): 166 - 170. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. B. Moeder, J. M. Giltnane, M. Harigopal, A. Molinaro, A. Robinson, K. Gelmon, D. Huntsman, R. L. Camp, and D. L. Rimm Quantitative Justification of the Change From 10% to 30% for Human Epidermal Growth Factor Receptor 2 Scoring in the American Society of Clinical Oncology/College of American Pathologists Guidelines: Tumor Heterogeneity in Breast Cancer and Its Implications for Tissue Microarray Based Assessment of Outcome J. Clin. Oncol., December 1, 2007; 25(34): 5418 - 5425. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Arnould, P. Arveux, J. Couturier, M. Gelly-Marty, C. Loustalot, F. Ettore, C. Sagan, M. Antoine, F. Penault-Llorca, B. Vasseur, et al. Pathologic Complete Response to Trastuzumab-Based Neoadjuvant Therapy Is Related to the Level of HER-2 Amplification Clin. Cancer Res., November 1, 2007; 13(21): 6404 - 6409. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. P. Coudert, R. Largillier, L. Arnould, P. Chollet, M. Campone, D. Coeffic, F. Priou, J. Gligorov, X. Martin, V. Trillet-Lenoir, et al. Multicenter Phase II Trial of Neoadjuvant Therapy With Trastuzumab, Docetaxel, and Carboplatin for Human Epidermal Growth Factor Receptor-2 Overexpressing Stage II or III Breast Cancer: Results of the GETN(A)-1 Trial J. Clin. Oncol., July 1, 2007; 25(19): 2678 - 2684. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Barrett, H. Magee, D. O'Toole, S. Daly, and M. Jeffers Amplification of the HER2 gene in breast cancers testing 2+ weak positive by HercepTest immunohistochemistry: false-positive or false-negative immunohistochemistry? J. Clin. Pathol., June 1, 2007; 60(6): 690 - 693. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Ross, W. F. Symmans, L. Pusztai, and G. N. Hortobagyi Standardizing Slide-Based Assays in Breast Cancer: Hormone Receptors, HER2, and Sentinel Lymph Nodes Clin. Cancer Res., May 15, 2007; 13(10): 2831 - 2835. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Dendukuri, K. Khetani, M. McIsaac, and J. Brophy Testing for HER2-positive breast cancer: a systematic review and cost-effectiveness analysis Can. Med. Assoc. J., May 8, 2007; 176(10): 1429 - 1434. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A Di Leo The state of HER-2 status Ann. Onc., May 1, 2007; 18(5): 813 - 815. [Full Text] [PDF]
|
|
|
|
|
|
A. C. Wolff, M. E. H. Hammond, J. N. Schwartz, K. L. Hagerty, D. C. Allred, R. J. Cote, M. Dowsett, P. L. Fitzgibbons, W. M. Hanna, A. Langer, et al. American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations for Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer J. Clin. Oncol., January 1, 2007; 25(1): 118 - 145. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Gonzalez-Angulo, G. N. Hortobagyi, and F. J. Esteva Adjuvant Therapy with Trastuzumab for HER-2/neu-Positive Breast Cancer Oncologist, September 1, 2006; 11(8): 857 - 867. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Pusztai, C. Mazouni, K. Anderson, Y. Wu, and W. F. Symmans Molecular Classification of Breast Cancer: Limitations and Potential Oncologist, September 1, 2006; 11(8): 868 - 877. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. A. Perez, V. J. Suman, N. E. Davidson, S. Martino, P. A. Kaufman, W. L. Lingle, P. J. Flynn, J. N. Ingle, D. Visscher, and R. B. Jenkins HER2 Testing by Local, Central, and Reference Laboratories in Specimens From the North Central Cancer Treatment Group N9831 Intergroup Adjuvant Trial J. Clin. Oncol., July 1, 2006; 24(19): 3032 - 3038. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Anderson, K. R. Hess, M. Kapoor, S. Tirrell, J. Courtemanche, B. Wang, Y. Wu, Y. Gong, G. N. Hortobagyi, W. F. Symmans, et al. Reproducibility of Gene Expression Signature-Based Predictions in Replicate Experiments Clin. Cancer Res., March 15, 2006; 12(6): 1721 - 1727. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. M. McShane, D. G. Altman, W. Sauerbrei, S. E. Taube, M. Gion, and G. M. Clark Reporting Recommendations for Tumor Marker Prognostic Studies J. Clin. Oncol., December 20, 2005; 23(36): 9067 - 9072. [Full Text] [PDF]
|
|
|
|
|
|
M. F. Press, G. Sauter, L. Bernstein, I. E. Villalobos, M. Mirlacher, J.-Y. Zhou, R. Wardeh, Y.-T. Li, R. Guzman, Y. Ma, et al. Diagnostic Evaluation of HER-2 as a Molecular Target: An Assessment of Accuracy and Reproducibility of Laboratory Testing in Large, Prospective, Randomized Clinical Trials Clin. Cancer Res., September 15, 2005; 11(18): 6598 - 6607. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. M. McShane, D. G. Altman, W. Sauerbrei, S. E. Taube, M. Gion, G. M. Clark, and for the Statistics Subcommittee of the NCI-EORTC W Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK) J Natl Cancer Inst, August 17, 2005; 97(16): 1180 - 1184. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Baselga, X. Carbonell, N.-J. Castaneda-Soto, M. Clemens, M. Green, V. Harvey, S. Morales, C. Barton, and P. Ghahramani Phase II Study of Efficacy, Safety, and Pharmacokinetics of Trastuzumab Monotherapy Administered on a 3-Weekly Schedule J. Clin. Oncol., April 1, 2005; 23(10): 2162 - 2171. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Al-Kuraya, P. Schraml, J. Torhorst, C. Tapia, B. Zaharieva, H. Novotny, H. Spichtin, R. Maurer, M. Mirlacher, O. Kochli, et al. Prognostic Relevance of Gene Amplifications and Coamplifications in Breast Cancer Cancer Res., December 1, 2004; 64(23): 8534 - 8540. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Th. Went, S. Dirnhofer, M. Bundi, M. Mirlacher, P. Schraml, S. Mangialaio, S. Dimitrijevic, J. Kononen, A. Lugli, R. Simon, et al. Prevalence of KIT Expression in Human Tumors J. Clin. Oncol., November 15, 2004; 22(22): 4514 - 4522. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Bernard-Marty, F. Cardoso, and M. J. Piccart Facts and Controversies in Systemic Treatment of Metastatic Breast Cancer Oncologist, November 1, 2004; 9(6): 617 - 632. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Isola, M. Tanner, A. Forsyth, T. G. Cooke, A. D. Watters, and J. M. S. Bartlett Interlaboratory Comparison of HER-2 Oncogene Amplification as Detected by Chromogenic and Fluorescence in situ Hybridization Clin. Cancer Res., July 15, 2004; 10(14): 4793 - 4798. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. D. Pegram, T. Pienkowski, D. W. Northfelt, W. Eiermann, R. Patel, P. Fumoleau, E. Quan, J. Crown, D. Toppmeyer, M. Smylie, et al. Results of Two Open-Label, Multicenter Phase II Studies of Docetaxel, Platinum Salts, and Trastuzumab in HER2-Positive Advanced Breast Cancer J Natl Cancer Inst, May 19, 2004; 96(10): 759 - 769. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Yaziji, L. C. Goldstein, T. S. Barry, R. Werling, H. Hwang, G. K. Ellis, J. R. Gralow, R. B. Livingston, and A. M. Gown HER-2 Testing in Breast Cancer Using Parallel Tissue-Based Methods JAMA, April 28, 2004; 291(16): 1972 - 1977. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. L. Wiley and L. K. Diaz High-Quality HER-2 Testing: Setting a Standard for Oncologic Biomarker Assessment JAMA, April 28, 2004; 291(16): 2019 - 2020. [Full Text] [PDF]
|
|
|
|
 |
|
 L. K. Diaz, R. Gupta, N. Kidwai, N. Sneige, and E. L. Wiley The Use of TMA for Interlaboratory Validation of FISH Testing for Detection of HER2 Gene Amplification in Breast Cancer J. Histochem. Cytochem., April 1, 2004; 52(4): 501 - 507. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. B. Elkin, M. C. Weinstein, E. P. Winer, K. M. Kuntz, S. J. Schnitt, and J. C. Weeks HER-2 Testing and Trastuzumab Therapy for Metastatic Breast Cancer: A Cost-Effectiveness Analysis J. Clin. Oncol., March 1, 2004; 22(5): 854 - 863. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I O Ellis, J Bartlett, M Dowsett, S Humphreys, B Jasani, K Miller, S E Pinder, A Rhodes, and R Walker Best Practice No 176: Updated recommendations for HER2 testing in the UK J. Clin. Pathol., March 1, 2004; 57(3): 233 - 237. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E D Hsi and R R Tubbs Guidelines for HER2 testing in the UK J. Clin. Pathol., March 1, 2004; 57(3): 241 - 242. [Full Text] [PDF]
|
|
|
|
|
|
R. Nahta and F. J. Esteva HER-2-Targeted Therapy: Lessons Learned and Future Directions Clin. Cancer Res., November 1, 2003; 9(14): 5078 - 5084. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. T. Junttila, M. Laato, T. Vahlberg, K.-O. Soderstrom, T. Visakorpi, J. Isola, and K. Elenius Identification of Patients with Transitional Cell Carcinoma of the Bladder Overexpressing ErbB2, ErbB3, or Specific ErbB4 Isoforms: Real-Time Reverse Transcription-PCR Analysis in Estimation of ErbB Receptor Status from Cancer Patients Clin. Cancer Res., November 1, 2003; 9(14): 5346 - 5357. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Atalay, F. Cardoso, A. Awada, and M. J. Piccart Novel therapeutic strategies targeting the epidermal growth factor receptor (EGFR) family and its downstream effectors in breast cancer Ann. Onc., September 1, 2003; 14(9): 1346 - 1363. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Ross, J. A. Fletcher, G. P. Linette, J. Stec, E. Clark, M. Ayers, W. F. Symmans, L. Pusztai, and K. J. Bloom The HER-2/neu Gene and Protein in Breast Cancer 2003: Biomarker and Target of Therapy Oncologist, August 1, 2003; 8(4): 307 - 325. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Vincent-Salomon, G. MacGrogan, J. Couturier, L. Arnould, and S. Mathoulin-Pelissier Re: HER2 Testing in the Real World J Natl Cancer Inst, April 16, 2003; 95(8): 628 - 628. [Full Text] [PDF]
|
|
|
|
|
|
R. L. Camp, M. Dolled-Filhart, B. L. King, and D. L. Rimm Quantitative Analysis of Breast Cancer Tissue Microarrays Shows That Both High and Normal Levels of HER2 Expression Are Associated with Poor Outcome Cancer Res., April 1, 2003; 63(7): 1445 - 1448. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Nahta, G. N. Hortobagyi, and F. J. Esteva Growth Factor Receptors in Breast Cancer: Potential for Therapeutic Intervention Oncologist, February 1, 2003; 8(1): 5 - 17. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Zujewski "Build Quality in"--HER2 Testing in the Real World J Natl Cancer Inst, June 5, 2002; 94(11): 788 - 789. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||