Breast Neoplasms: Hammond ME

Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, Dowsett M, Fitzgibbons PL, Hanna WM, Langer A, McShane LM, Paik S, Pegram MD, Perez EA, Press MF, Rhodes A, Sturgeon C, Taube SE, Tubbs R, Vance GH, van de Vijver M, Wheeler TM, Hayes DF, Anonymous00094. · American Society of Clinical Oncology, Alexandria, VA; and the College of American Pathologists, Northfield, IL, USA. · Arch Pathol Lab Med. · Pubmed #19548375 No free full text.

Abstract: PURPOSE: To develop a guideline to improve the accuracy of human epidermal growth factor receptor 2(HER2) testing in invasive breast cancer and its utility as a predictive marker. METHODS: The American Society of Clinical Oncology and the College of American Pathologists convened an expert panel, which conducted a systematic review of the literature and developed recommendations for optimal HER2 testing performance. The guideline was reviewed by selected experts and approved by the board of directors for both organizations. RESULTS: Approximately 20% of current HER2 testing may be inaccurate. When carefully validated testing is performed, available data do not clearly demonstrate the superiority of either immunohistochemistry(IHC) or in situ hybridization (ISH) as a predictor of benefit from anti-HER2 therapy. RECOMMENDATIONS: The panel recommends that HER2 status should be determined for all invasive breast cancer. A testing algorithm that relies on accurate, reproducible assay performance, including newly available types of brightfield ISH, is proposed. Elements to reliably reduce assay variation (for example, specimen handling, assay exclusion, and reporting criteria) are specified. An algorithm defining positive, equivocal, and negative values for both HER2 protein expression and gene amplification is recommended: a positive HER2 result is IHC staining of 3 + (uniform, intense membrane staining of 30% of invasive tumor cells), a fluorescent in situ hybridization (FISH) result of more than six HER2 gene copies per nucleus or a FISH ratio (HER2 gene signals to chromosome 17 signals) of more than 2.2; a negative result is an IHC staining of 0 or 1 +, a FISH result of less than 4.0 HER2 gene copies per nucleus, or FISH ratio of less than 1.8. Equivocal results require additional action for final determination. It is recommended that to perform HER2 testing, laboratories show 95% concordance with another validated test for positive and negative assay values. The panel strongly recommends validation of laboratory assay or modifications, use of standardized operating procedures, and compliance with new testing criteria to be monitored with the use of stringent laboratory accreditation standards, proficiency testing, and competency assessment. The panel recommends that HER2 testing be done in a CAP-accredited laboratory or in a laboratory that meets the accreditation and proficiency testing requirements set out by this document.

Vance GH, Barry TS, Bloom KJ, Fitzgibbons PL, Hicks DG, Jenkins RB, Persons DL, Tubbs RR, Hammond ME, Anonymous00034. · Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA. · Arch Pathol Lab Med. · Pubmed #19391661 No free full text.

Abstract: CONTEXT: Intratumoral heterogeneity of HER2 gene amplification has been well documented and represents subclonal diversity within the tumor. The reported incidence of intratumor HER2 amplification genetic heterogeneity ranges in the literature from approximately 5% to 30%. The presence of HER2 genetic heterogeneity may increase subjectivity in HER2 interpretation by the pathologist. OBJECTIVES: To define HER2 genetic heterogeneity and to provide practice guidelines for examining and reporting breast tumors with genetic heterogeneity for improvement of HER2 testing in breast cancer. DESIGN: We convened an expert panel to discuss HER2 gene amplification testing by fluorescence in situ hybridization. Components addressed included a definition of HER2 amplification heterogeneity, practice guidelines for examination of the tissue, and reporting criteria for this analysis. RESULTS: Genetic heterogeneity for amplification of HER2 gene status in invasive breast cancer is defined and guidelines established for assessing and reporting HER2 results in these cases. These guidelines are additive to and expand those published in 2007 by the American Society of Clinical Oncology and the College of American Pathologists. CONCLUSION: Standardized methods for analysis will improve the accuracy and consistency of interpretation of HER2 gene amplification status in breast cancer.

Carlson RW, Moench SJ, Hammond ME, Perez EA, Burstein HJ, Allred DC, Vogel CL, Goldstein LJ, Somlo G, Gradishar WJ, Hudis CA, Jahanzeb M, Stark A, Wolff AC, Press MF, Winer EP, Paik S, Ljung BM, Anonymous00047. · Stanford Hospital and Clinics. · J Natl Compr Canc Netw. · Pubmed #16813731 No free full text.

Abstract: The NCCN HER2 Testing in Breast Cancer Task Force was convened to critically evaluate the ability of the level of HER2 expression or gene amplification in breast cancer tumors to serve as a prognostic and a predictive factor in the metastatic and adjuvant settings, to assess the reliability of the methods of measuring HER2 expression or gene amplification in the laboratory, and to make recommendations regarding the interpretation of test results. The Task Force is a multidisciplinary panel of 24 experts in breast cancer representing the disciplines of medical oncology, pathology, radiation oncology, surgical oncology, epidemiology, and patient advocacy. Invited members included members of the NCCN Breast Cancer Panel and other needed experts selected solely by the NCCN. During a 2-day meeting, individual task force members provided didactic presentations critically evaluating important aspects of HER2 biology and epidemiology: HER2 as a prognostic and predictive factor; results from clinical trials in which trastuzumab was used as a targeted therapy against HER2 in the adjuvant and metastatic settings; the available testing methodologies for HER2, including sensitivity, specificity, and ability to provide prognostic and predictive information; and the principles on which HER2 testing should be based. Each task force member was charged with identifying evidence relevant to their specific expertise and presentation. Following the presentations, an evidence-based consensus approach was used to formulate recommendations relating to the pathologic and clinical application of the evidence to breast cancer patient evaluation and care. In areas of controversy, this process extended beyond the meeting to achieve consensus. The Task Force concluded that accurate assignment of the HER2 status of invasive breast cancer is essential to clinical decision making in the treatment of breast cancer in both adjuvant and metastatic settings. Formal validation and concordance testing should be performed and reported by laboratories performing HER2 testing for clinical purposes. If appropriate quality control/assurance procedures are in place, either immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH) methods may be used. A tumor with an IHC score of 0 or 1+, an average HER2 gene/chromosome 17 ratio of less than 1.8, or an average number of HER2 gene copies/cell of 4 or less as determined by FISH is considered to be HER2 negative. A tumor with an IHC score of 3+, an average HER2 gene/chromosome 17 ratio of greater than 2.2 by FISH, or an average number of HER2 gene copies/cell of 6 or greater is considered HER2 positive. A tumor with an IHC score of 2+ should be further tested using FISH, with HER2 status determined by the FISH result. Tumor samples with an average HER2 gene/chromosome ratio of 1.8 to 2.2 or average number of HER2 gene copies/cell in the range of greater than 4 to less than 6 are considered to be borderline, and strategies to assign the HER2 status of such samples are proposed.

Hicks DG, Kulkarni S, Hammond ME. · No affiliation provided · Arch Pathol Lab Med. · Pubmed #18684020 No free full text.

This publication has no abstract.

Hammond ME, Fitzgibbons PL, Compton CC, Grignon DJ, Page DL, Fielding LP, Bostwick D, Pajak TF. · LDS Hospital and University of Utah School of Medicine, Salt Lake City, Utah, USA. · Arch Pathol Lab Med. · Pubmed #10888771 No free full text.

Abstract: The College of American Pathologists convened a prognostic factor conference in June 1999 to consider prognostic and predictive factors in breast, colon, and prostate cancer, and to stratify these factors into categories reflecting the strength of published evidence. Because so little progress in prognostic factor clinical utility has been made in the last 5 years, the conference participants focused their attention on decreasing variation in methods, interpretation, and reporting of these factors so that greater clarity of value could be achieved. The conference was organized to promote discussion, broad input, and future planning. An initial plenary session provided an overview of the status of tumor marker research, the impact of variation in medicine and pathology, and statistical issues related to prognostic factor research. In working group sessions for each cancer type, participants interactively evaluated and refined the documents created by the expert panels. A second plenary session dealt with issues common to all 3 groups, including the problem of micrometastases in lymph nodes in these sites; statistical issues that arose during the breakout discussions; and issues of variation in methods, interpretation, and reporting of immunohistochemical assays. A faculty session brainstormed strategies that could be used to implement the changes recommended. This session included invited representatives of the Food and Drug Administration, Health Care Financing Administration, Centers for Disease Control and Prevention, National Cancer Institute, American Joint Committee on Cancer, and International Union Against Cancer. Cancer site and general recommendations were presented and discussed during a final session to achieve consensus of the conference participants and to address feasibility of implementation of these recommendations. A final discussion focused on future initiatives that might lead to implementation of the changes proposed in the conference by the various organizations represented. This report summarizes the general conference recommendations, cancer working group recommendations, and plans for implementation of the recommendations.

Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, Dowsett M, Fitzgibbons PL, Hanna WM, Langer A, McShane LM, Paik S, Pegram MD, Perez EA, Press MF, Rhodes A, Sturgeon C, Taube SE, Tubbs R, Vance GH, van de Vijver M, Wheeler TM, Hayes DF, Anonymous00055, Anonymous00056. · American Society of Clinical Oncology, Alexandria, VA, USA. · J Clin Oncol. · Pubmed #17159189 No free full text.

Abstract: PURPOSE: To develop a guideline to improve the accuracy of human epidermal growth factor receptor 2 (HER2) testing in invasive breast cancer and its utility as a predictive marker. METHODS: The American Society of Clinical Oncology and the College of American Pathologists convened an expert panel, which conducted a systematic review of the literature and developed recommendations for optimal HER2 testing performance. The guideline was reviewed by selected experts and approved by the board of directors for both organizations. RESULTS: Approximately 20% of current HER2 testing may be inaccurate. When carefully validated testing is performed, available data do not clearly demonstrate the superiority of either immunohistochemistry (IHC) or in situ hybridization (ISH) as a predictor of benefit from anti-HER2 therapy. RECOMMENDATIONS: The panel recommends that HER2 status should be determined for all invasive breast cancer. A testing algorithm that relies on accurate, reproducible assay performance, including newly available types of brightfield ISH, is proposed. Elements to reliably reduce assay variation (for example, specimen handling, assay exclusion, and reporting criteria) are specified. An algorithm defining positive, equivocal, and negative values for both HER2 protein expression and gene amplification is recommended: a positive HER2 result is IHC staining of 3+ (uniform, intense membrane staining of > 30% of invasive tumor cells), a fluorescent in situ hybridization (FISH) result of more than six HER2 gene copies per nucleus or a FISH ratio (HER2 gene signals to chromosome 17 signals) of more than 2.2; a negative result is an IHC staining of 0 or 1+, a FISH result of less than 4.0 HER2 gene copies per nucleus, or FISH ratio of less than 1.8. Equivocal results require additional action for final determination. It is recommended that to perform HER2 testing, laboratories show 95% concordance with another validated test for positive and negative assay values. The panel strongly recommends validation of laboratory assay or modifications, use of standardized operating procedures, and compliance with new testing criteria to be monitored with the use of stringent laboratory accreditation standards, proficiency testing, and competency assessment. The panel recommends that HER2 testing be done in a CAP-accredited laboratory or in a laboratory that meets the accreditation and proficiency testing requirements set out by this document.

Zarbo RJ, Hammond ME. · Department of Pathology, Henry Ford Hospital and Medical Group, Detroit, Mich 48202, USA. · Arch Pathol Lab Med. · Pubmed #12708896 No free full text.

Abstract: CONTEXT: Practicing pathologists often encounter controversial clinical issues and nonstandardized laboratory approaches to the evolving science of predictive/prognostic tumor marker assays. This dilemma becomes especially acute when the assay is the sole determinant for selection of a specific therapy. OBJECTIVES: To summarize the areas of practical agreement and identify opportunities for improvement in Her-2/neu testing of breast cancer. DESIGN: The College of American Pathologists created a new comprehensive education model, called Strategic Science, with expert speakers integrating new and evolving basic, clinical, and scientific issues of Her-2/neu testing with aspects of laboratory management. SETTING: Symposium held May 4 and 5, 2002, in Rosemont, Ill. PARTICIPANTS: Ten speakers and more than 100 attendees. RESULTS: Components addressed were new technology assessment, practice guidelines, quality assurance, regulatory compliance, risk and liability, billing and coding, cost analysis, consultation, information management, and results reporting. CONCLUSIONS: This Strategic Science symposium derived areas of practical agreement, defined the current state-of-the-art, and identified areas for improvement in Her-2/neu testing.