B9
Borderline HER2 protein positive breast cancers have similar patient outcome regardless of HER2 gene amplification status
Fabricio Barros, Mohammed Aleskandarany, Emad Rakha, Sarah Watts, Claire Paish, Ian Ellis, Andy Green
University of Nottingham and Nottingham City Hospitals NHS Trust, UK
Background
HER2 plays an important role in breast cancer progression and provides predictive and prognostic information. HER2 status is currently assessed in routine breast cancer reporting using immunohistochemistry (IHC) in addition to in situ hybridisation (ISH) in borderline cases. The ability of HER2 gene status to predict response to targeted therapy (Herceptin) is well documented. However, prognostic information provided by IHC expression categories and prognostic value added by using ISH in borderline cases remains unclear.
Method
In this study, we have assessed HER2 status in a large well-characterised breast cancer series prepared as tissue microarray (n=1858) using IHC (HercepTest, DakoCytomation) and chromogenic ISH (CISH; DuoCISH, as an extension to HER2 FISH pharmDx; DakoCytomation) in order to identify relationships with clinico-pathological variables and patient outcome.
Results
There was excellent overall concordance between HercepTest negative (scores 0/1+) and positive (3+) with CISH positive/negative (defined as HER2/Chr17 copy number ratio of ≥2; p<0.001). Of the 74 borderline HercepTest 2+ cases (n=44), 59% showed HER2 gene amplification. 12% of cases were identified as HER2 positive (those with 3+ HercepTest scores or 2+ with gene amplification). Kaplan-Meier analysis for breast cancer specific (BCSS) and disease free survival (DFS) revealed statistically significant differences between HER2 positive and negative cases detected by HercepTest and CISH (p<0.001). Interestingly, we identified that HercepTest 2+ non-amplified cases were not significantly different with those amplified 2+ or 3+ cases with respect to their behaviour (BCSS and DFS).
Conclusion
The overall concordance between HercepTest and CISH analysis for HER2 status was excellent. All HercepTest 2+ cases identified were observed to have poor outcomes similar to those HercepTest 3+ cases regardless of gene amplification status. In the current clinical environment cases exhibiting IHC 2+ and non-amplified gene HER2 status will not be offered targeted HER2 therapy but do exhibit aggressive clinical behavioural characteristics.
