A total of 592 primary invasive BC cases from before and after the publication of the updated ASCO/CAP guideline were evaluated for HER2 amplification by silver ISH according to the 2013 and 2018 guidelines.
For dual probe HER2 FISH assay, the 2013 CAP/ASCO guideline recommendations lowered the HER2/CEP17 ratio cut off for HER2 amplification to ≥2.0 and introduced an average HER2 copy number criterion for HER2 amplification (≥6.0/cell) and HER2 equivocal categories (≥4 and <6/cell).
Nine (13%) cases showed HER2 amplification by CISH, whereas 14 (20%) and 28 (40%) cases showed overexpression with IHC when the 2007 or 2013 ASCO/CAP criteria were utilized, respectively.
The routine assessment of HER2/neu amplification using the ASCO/CAP criteria on whole tissue sections is not significantly confounded by intratumoral heterogeneity in breast cancer with high-grade amplification; however, genetic heterogeneity exists in a subset of breast carcinomas with low-grade amplification.