ideasIdea
Calibrated reference slides so every lab scores HER2-low the same way
Whether a breast cancer counts as 'HER2-low', and so qualifies for a powerful drug, depends on which lab reads the slide. Standard reference slides with known HER2 levels would make the answer consistent.
T-DXd approval for HER2-low created a treatment decision at IHC 1+ versus 0, the least reproducible part of the HER2 scale, with inter-pathologist agreement reported as poor. Cell-line microarrays with quantified HER2 protein per cell, distributed as reference materials and run alongside clinical slides (as NordiQC and CAP do for proficiency testing), would anchor staining intensity and scoring to a physical standard, complemented by digital image analysis calibrated to the same materials.
Hypothesis
Laboratories using calibrated reference materials will show inter-laboratory agreement on HER2 0 versus 1+ above 85%, compared with the 60 to 70% reported in current concordance studies.
Rationale
Reference materials transformed reproducibility in clinical chemistry. Pathology has proficiency schemes but few quantitative anchors for low-level protein expression.
What would test it
Distribute reference arrays to 50 laboratories with a blinded set of clinical cases; measure agreement with and without reference calibration.
Maturity
early clinical
Who has to act
regulator
Cost to try
Small (under $1M)
Years to first evidence
2
Bottlenecks it attacks
- Biomarkers are not validated or standardised · Tests that decide who gets a drug are often not validated prospectively and are measured differently in every lab.