How Can HER2DX Testing Improve Management of Early-Stage HER2-Positive Breast Cancer?

Outcomes of human epidermal growth factor receptor 2 (HER2)-positive breast cancer have improved significantly alongside the development of new therapies. Even so, biological and clinical heterogeneity continue to create variability in prognosis and treatment sensitivity in early-stage disease, leading to uncertainty about how to tailor treatment intensity to specific patients.

HER2DX, a genomic-clinical test that integrates tumor biology with key clinical variables, can support individualized decision-making in early-stage HER2-positive breast cancer. The test generates three clinically relevant outputs, including a prognostic relapse risk score, a pathological complete response (pCR) score, and an ERBB2 messenger RNA expression score.

A substantial body of evidence on HER2DX’s clinical utility has emerged since its development. In a review published in ESMO Open, Sara M. Tolaney, MD, and colleagues summarize the evidence and outline practical considerations for integrating it into clinical practice.

The review outlines the literature on each of the test’s three scores. First, they examine the HER2DX risk score, which is independently associated with survival across clinically relevant subgroups, thereby aiding adjuvant therapy decision-making by providing information about expected outcomes.

Next, the authors discuss the pCR score, which estimates the patient’s probability of achieving a pCR and can identify patient subgroups with distinct response profiles. This score is useful in neoadjuvant decision-making and should be interpreted alongside the HER2DX risk score, as the two scores provide separate but complementary information.

Lastly, the authors discuss the HER2DX ERBB2 score, which measures ERBB2 expression and predicts clinical HER2 status. Research indicates that HER2DX ERBB2-low tumors may be biologically and pathologically heterogenous and less sensitive to anti-HER2-based therapies, meaning that this score could be beneficial in treatment decisions by helping physicians select the most promising treatment for each patient and avoid prescribing unnecessary interventions.

Overall, the authors note that HER2DX can support individualized treatment discussions, though it should not be used as a standalone decision-making tool because prospective validation of HER2DX-informed treatment decisions is still in progress.