An updated review gathers the available evidence on HER2DX, a genomic and clinical test designed to help individualise treatment in early-stage HER2-positive breast cancer. The tool integrates biological features of the tumour with clinical variables to guide treatment intensity.
What was known
Treatments targeting HER2 have greatly improved outcomes in this subtype, but marked biological and clinical heterogeneity persists, driving variation in prognosis and treatment sensitivity. Guidelines provide broad frameworks, but uncertainty remains when adjusting treatment intensity to each patient.
What this work adds
HER2DX was developed to support individualised decisions in stage I to III HER2-positive breast cancer, combining tumour biology with key clinical variables such as tumour size and nodal status. The test generates three relevant outputs: a prognostic relapse risk score, a probability score for pathological complete response and an ERBB2 messenger RNA expression score. The review synthesises the evidence generated since its original development.
Main results
Large international individual-patient-level meta-analyses have demonstrated independent associations between the HER2DX risk score and survival, and between the complete-response score and pathologically confirmed response, beyond standard clinicopathological factors. Translational studies show that HER2DX captures complementary biological features, such as hormone receptor signalling, proliferation, HER2 pathway activation and immune infiltration and organisation, that are not fully reflected by conventional pathology. Prospective evaluations, including prespecified analyses from the ECOG-ACRIN EA1181 CompassHER2 trial and a Spanish multicentre study on the impact on real-world decisions, provide further evidence on its potential clinical application.
What it means
The review discusses how to integrate HER2DX into clinical practice to optimise treatment intensity, escalating or de-escalating it according to risk and the likelihood of response. For a patient, it is an additional decision-support tool rather than a treatment in itself, and it favours better-informed conversations about therapy intensity. For breast units, it means incorporating genomic tests with judgement and taking account of the care setting.
Spanish context
The evidence gathered includes a Spanish multicentre study on the impact of the test on real clinical decisions, placing Spanish hospitals in the practical evaluation of HER2DX. Medical oncology and pathology departments in the country take part in validating and using genomic platforms, within a growing trend towards personalised medicine in breast units.
Reference: Tolaney SM, Tung N, Wolff AC, DeMichele A, Cejalvo JM, Martínez-Sáez O, et al. HER2DX in early-stage HER2-positive breast cancer: a review of clinical utility. ESMO Open, 2026. DOI
