OUP user menu

HER-2/neu Assessment in Breast Cancer Using the Original FDA and New ASCO/CAP Guideline Recommendations
Impact on Selecting Patients for Herceptin Therapy

Matteo Brunelli MD, Erminia Manfrin MD, Guido Martignoni MD, Samantha Bersani BaD, Andrea Remo MD, Daniela Reghellin MD, Marco Chilosi MD, Franco Bonetti MD
DOI: http://dx.doi.org/10.1309/MD79CDXN1D01E862 907-911 First published online: 1 June 2008


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.

Key Words:
  • HER-2/neu
  • Immunohistochemistry
  • Fluorescence in situ hybridization
  • FISH
  • FDA