Trastuzumab deruxtecan (Enhertu®) has shown significant anti-tumour efficacy against HER2-low-expressing metastatic breast cancer (mBC) and has received approval in the US and Europe in this setting. Identification of patients with the potential to respond to the therapy relies on assessment of HER2 protein expression at a low level, a category not considered clinically significant previously. We report on a study examining testing proficiency in this area.
UK NEQAS ICC & ISH recruited 45 laboratories from its participants that regularly undertake clinical BC testing. They were provided with BC tissues in which HER2 expression levels had been established independently in two reference laboratories, both using the approved immunohistochemical (IHC) assay (4B5, Ventana) according to manufacturer’s instructions. Expression levels were consistently shown to be: 1+ on tumour A; variably 1+ or 0 on tumour B; 0 on tumour C; and 2+ on tumour D. Laboratories were asked to demonstrate HER2 by IHC and then interpret the staining.
39 (86.7%) laboratories used an approved assay (4B5, Ventana), the remaining 6 (13.3%) employed a variety of primary antibodies in laboratory developed tests (LDTs). Overall, 22 (56.4%) of those using the 4B5 assay achieved results concordant with the expected reference levels in all 4 tumours when they were assessed by an expert panel; none (0.0%) of the laboratories using an LDT achieved the expected levels of staining. Interpretive performance was assessed for each of the 4 BC samples: 14 (41.2%) were concordant with the reference score on tumour A; 17 (47.2%) on tumour B; 30 (83.3%) on tumour C; and 23 (63.9%) on tumour D. The combined technical and interpretative performance assessment showed: 8 (38.1%) laboratories achieved the expected staining levels and interpretation on tumour A; 17 (47.2%) on tumour B; 30 (83.3%) on tumour C; and 15 (41.7%) on tumour D.
The study indicates that in the HER2-low expression range, BC samples when tested for HER2 expression in clinical laboratories produce scores showing poor agreement (<50%) with those obtained using a well-validated assay interpreted by experts.
External Quality Assessment Services for Cancer Diagnostics CIC.
AstraZeneca UK LTD.
S. Parry: Financial Interests, Institutional, Other, Joint project: Diaceutics; Financial Interests, Personal, Advisory Board: AbbVie. A. Shaaban: Financial Interests, Personal, Advisory Board: AstraZeneca, Diaceutics; Financial Interests, Personal, Invited Speaker: Ventana Roche, Exact Science, Prosigna. A. Dodson: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Other, Lead joint project: Diaceutics. All other authors have declared no conflicts of interest.