Improving HER2 classification with molecular testing

Human epidermal growth factor receptor 2 (HER2) scoring in breast cancer traditionally labelled tumours as either positive or negative but, more recently, HER2-low breast cancer has been recognised as a clinically relevant subset. This shift introduces challenges for diagnosis, as immunohistochemistry (IHC) – the gold standard diagnostic method – is prone to subjectivity and poor reproducibility when distinguishing between HER2 0, 1+ and 2+. Borderline cases can be ambiguous, and studies from across the UK and Europe have shown poor agreement in HER2-low scoring between different pathologists, raising concerns over consistency in routine practice. This article explores the limitations of current diagnostic workflows and discusses the role of RT-qPCR-based molecular subtyping as a complementary approach to improve reproducibility and support IHC interpretation.

HER2 is a transmembrane receptor tyrosine kinase that is vital for cell growth and survival. It was first identified as a breast cancer biomarker in 2005, and soon became the primary indicator for stratifying patients at initial diagnosis.³ HER2 status went on to also be used to determine the best treatment option, primarily to determine whether HER2-targeted agents such as pertuzumab, trastuzumab and trastuzumab emtansine (T-DM1) would be effective.^4-6 Patients were traditionally classed into two categories: HER2-negative or HER2-positive, which guided the use of these therapies. 

Current testing protocols