In Australia, Medicare-funded access to effective HER2-targeted therapies requires demonstration of HER2 positivity by in-situ hybridisation (ISH) amplification, regardless of immunohistochemistry status (IHC 3+). This is at odds with the recently updated American Society of Clinical Oncology/College of American Pathologists (ASCO CAP) guidelines. Given this discrepancy in practice and significant additional cost, this study evaluated the frequency of discordance in using both assays in a historical series of patients with breast cancer.
A retrospective audit of HER2 histopathology reports was performed for all breast cancers diagnosed between 2011 and 2017 at Austin Health. The proportion of concordant (defined as IHC 0/1+ and negative ISH, samples with IHC3+ and positive ISH, and samples with IHC2+ regardless of ISH) and discordant results (defined as IHC 3+ and ISH non-amplified or IHC 0/1+ and ISH amplified) were analysed.
Eight hundred and forty-six histopathology reports were reviewed from 786 patients. There were 10 discordant cases (1.2%), including three (0.4%) with a negative IHC (1+) but positive ISH, and 7 cases (0.8%) with a positive IHC but negative ISH. Access to funded therapy remained unchanged in 665 (79.0%) cases, implying $209,741 was spent on unnecessary ISH testing. Victorian Cancer Registry data from 13 898 breast cancers from 2008-2016 revealed a similarly low rate (1.5%) of cases with a negative IHC (1+) result but positive ISH, however 19.8% of patients with a positive IHC were found to have a negative ISH.
This study describes an extremely low rate of HER2 IHC/ISH discordance at a single institution suggesting that routine use of both assays is unnecessary in cases with unequivocal IHC. The negative predictive value of our IHC results is consistent with registry data, and provide a strong rationale for access to HER2 targeted therapies to be based IHC or ISH.