NEW ESMO OPEN REVIEW EXAMINES GROWING BODY OF EVIDENCE SUPPORTING HER2DX IN EARLY-STAGE HER2-POSITIVE BREAST CANCER

• Comprehensive review led by Dr. Sara M. Tolaney (Dana-Farber Cancer Institute) synthesizes evidence from thousands of patients on HER2DX in stage I-III HER2-positive breast cancer.
• Discusses prespecified findings from the phase II CompassHER2 pCR trial and the first real-world decision-impact study, in which HER2DX changed the planned treatment strategy in 48% of patients.
•  The review presents HER2DX as a complementary decision-support tool, with further validation underway through the randomized DEFINITIVE trial.
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REVEAL GENOMICS, S.L., a Barcelona-based biotechnology company focused on advancing precision oncology through biomarker innovation, today highlighted the recent publication of an independent review article in ESMO Open, the peer-reviewed journal of the European Society for Medical Oncology (ESMO). Authored by an international panel of breast cancer experts, the review synthesizes the growing body of clinical evidence supporting the use of HER2DX in the management of stage I-III HER2-positive breast cancer.

The review, titled "HER2DX in early-stage HER2-positive breast cancer: a review of clinical utility,"was led by Sara M. Tolaney, MD, MPH, Chief of the Division of Breast Oncology at Dana-Farber Cancer Institute, together with a panel of international breast cancer experts. The article reviews the growing body of clinical evidence on HER2DX: a prognostic relapse risk score, a pathological complete response (pCR) score, and an ERBB2 messenger RNA expression score, each designed to help clinicians tailor treatment intensity for patients with early-stage HER2-positive breast cancer.

Among the evidence discussed in the review is a published individual-patient-level meta-analysis of 2,518 patients from 11 independent studies, which confirmed that the HER2DX risk score is independently associated with event-free and overall survival across adjuvant and neoadjuvant treatment settings.

The review also discusses prespecified findings from the phase II CompassHER2 pCR trial, in which the HER2DX pCR score was assessed in 569 patients and showed clear, statistically significant separation in pathological complete response rates between HER2DX pCR-high and pCR-low tumors, independent ofstandard clinicopathological factors, including hormone receptor status.

"This review reflects how the evidence supporting HER2DX has matured over the past few years. We are pleased to see independent experts consolidate the available clinical data and highlight the potential of biological information to complement established clinicopathological factors in treatment decision-making for patients with early-stage HER2-positive breast cancer", says Dr. Aleix Prat, co-founder and chairman of the board at REVEAL GENOMICS.

The review also details results from the first prospective, real-world decision-impact study of HER2DX, conducted across 12 hospitals in Spain with 34 medical oncologists who had no prior experience using the assay. Among 297 patients with newly diagnosed stage I-III HER2-positive breast cancer, HER2DXresults led to a change in the planned treatment strategy in 48% of patients,most often toward reduced-intensity regimens, and were associated with increased physician-reported confidence in treatment decisions, whether or not the original plan was modified.

 The authors note that, despite this expanding evidence base, HER2DX should currently be interpreted as a complementary biological decision-support tool to be considered alongside established clinicopathological factors, rather than as a standalone determinant of treatment selection.

 Validation is ongoing through several trials, including the randomized, multicenter DEFINITIVE prospective trial, which is being conducted across 43 hospitals in Europe and Israel and is supported by the European Union's Horizon Europe Research and Innovation Programme.

What's Next for HER2DX

The authors note that as the treatment landscape for HER2-positive breast cancer continues to evolve, with the emergence of next-generation antibody-drug conjugates, tyrosine kinase inhibitors, selective estrogen receptor degraders,and immune-modulating therapies, biological stratification tools are expected to play an increasingly central role in both early-stage and metastatic disease. The authors also discuss, as a potential area for future investigation, whether biological profiling could help identify selected patients for chemotherapy-free approaches

HER2DX may help refine estimates of prognosis and treatment sensitivity as this complexity grows, supporting more individualized treatment discussions. Prospective randomized studies remain important to confirm whetherHER2DX-guided escalation or de-escalation strategies can safely optimize outcomes while reducing overtreatment; one potential future application is identifying patients who could achieve durable disease control with dual HER2blockade alone, without chemotherapy.

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