HER-2/neu assessment in breast cancer using the original FDA and new ASCO/CAP guideline recommendations: impact on selecting patients for herceptin therapy.

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.