HER2/neu gene determination in women screened for breast carcinoma: how screening programs reduce the skyrocketing cost of targeted therapy.

Few data on Human Epidermal Growth Factor Receptor 2 (HER2)-positive breast carcinomas have been reported for screen-detected breast carcinoma. Assessing the impact of a targeted intervention with anti-HER2 inhibitors on costs is required in order to plan for better strategies in screening programs. A total of 54,472 women were screened and 323 cases were found to be invasive cancer. We performed immunophenotypical-fluorescent in situ hybridization (FISH) analysis. Among 153 evaluable breast carcinomas, tumours displayed a 3+ scoring status 3+ in 16 (10%), 2+ in 12 (8%), 1+ in 29 (19%) and 0 in 96 (63%) of cases, respectively. All 3+ HER2+ cases and 2/12 2+ (17%) cases exhibited HER2/neu gene amplification, the remaining cases did not. In contrast to the higher incidence reported at the population level, 20-30% HER2-positive cases for metastatic carcinomas, and only 11% of the screen-detected breast carcinomas displayed HER2/neu gene amplification. Breast cancer detection by screening programs hijacks the skyrocketing cost of the use of targeted therapy in HER2-positive carcinoma.

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.