title: HER-2/neu assessment in breast cancer using the original FDA and new ASCO/CAP guideline recommendations: impact on selecting patients for herceptin therapy.
abstract: We evaluated HER-2/neu status in 100 consecutive ductal breast carcinomas by using the Food and Drug Administration (FDA) and American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) scoring systems. With the FDA system, scores were 3+ in 23.0%, 2+ in 25.0%, and 0 or 1+ in 52.0% of cases. With the ASCO/CAP system, scores were 3+ in 16.0%, 2+ in 34.0%, and 0 or 1+ in 50.0%. With the FDA and ASCO/CAP systems, respectively, 3+ cases (n = 23 and 16, respectively) showed high-grade, granular HER-2/neu amplification in 15 (65%) and 14 (88%); low-grade, borderline amplification in 7 (30%) and 1 (6%); and chromosome 17 polysomy without amplification in 1 (4%) and 1 (6%). Concordance between schemes was higher for cases with high-grade, granular HER-2/neu amplification (concordance coefficient, 0.74). Cases with low-grade, borderline HER-2/neu amplification showed poor concordance (concordance coefficient, 0.20). The FDA and ASCO/CAP schemes for HER-2/neu evaluation select patients differently for trastuzumab therapy. Major discordance is present for low-grade, borderline HER-2/neu amplification. FDA low-grade, borderline tumors would be reclassified as without HER-2/neu amplification or as polysomic. The ASCO/CAP scheme has a great concordance coefficient between strong 3+ immunohistochemical cases and cases with high-grade, granular HER-2/neu amplification.
authors.affiliation: Department of Pathology, Università di Verona, Verona, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Brunelli
authors.forename: Erminia
authors.initials: E
authors.lastname: Manfrin
authors.forename: Guido
authors.initials: G
authors.lastname: Martignoni
authors.forename: Samantha
authors.initials: S
authors.lastname: Bersani
authors.forename: Andrea
authors.initials: A
authors.lastname: Remo
authors.forename: Daniela
authors.initials: D
authors.lastname: Reghellin
authors.forename: Marco
authors.initials: M
authors.lastname: Chilosi
authors.forename: Franco
authors.initials: F
authors.lastname: Bonetti
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D018579:Patient Selection; D017410:Practice Guidelines as Topic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D012955:Societies, Medical; D000068878:Trastuzumab; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab