Nature Communications Study Supports HER2DX as a Genomic Tool for Tailored Therapy in Older Individuals With HER2+ Breast Cancer

First study to evaluate HER2DX in a randomized trial focused exclusively on older individuals (aged 70–80 years). HER2DX independently predicts long-term survival outcomes in patients treated with trastuzumab with or without chemotherapy. Findings support HER2DX as a tool to guide chemotherapy decisions and de-escalation strategies in older adults.

REVEAL GENOMICS, S.L., a Barcelona-based biotechnology company seeking to revolutionize precision oncology through biomarker innovation, today announced the publication of the study “HER2DX in older patients with HER2-positive early breast cancer: extended follow-up from the RESPECT trial of trastuzumab ± chemotherapy” in Nature Communications.

This landmark study evaluated the HER2DX genomic assay in 154 individuals aged 70–80 years enrolled in the RESPECT trial (NCT01104935), a randomized phase III study comparing adjuvant trastuzumab with or without chemotherapy. The analysis, known as Trans-RESPECT, is the first to evaluate HER2DX in an older adult population, a demographic historically underrepresented in clinical trials.

Bringing Precision Oncology to Older Individuals with HER2+ Disease
Despite the growing number of older adults diagnosed with HER2-positive early breast cancer, optimal treatment strategies remain unclear. Many face increased risks of chemotherapy-related toxicity, and current clinical-pathological tools often fall short in identifying those who may safely avoid chemotherapy.
By integrating tumor-intrinsic biology (including immune infiltration, proliferation, HER2 signaling, and luminal differentiation) with clinical features, the test HER2DX provides a comprehensive risk assessment tailored to the biology of HER2+ disease.

Revealing Key Findings from the RESPECT Trial Analysis
HER2DX testing was performed on tumor samples from the RESPECT trial, with a median follow-up of 9.3 years. The HER2DX risk score classified 74% of individuals as low-risk, and 26% as high-risk. Those in the low-risk group had significantly better 10-year relapse-free survival (77.9% vs. 68.0%) and overall survival (85.9% vs. 69.7%) compared to high-risk individuals.
HER2DX remained independently associated with overall survival in multivariable analysis, outperforming traditional factors such as tumor size, nodal status, and hormone receptor expression. The assay’s immune, luminal, and proliferation signatures were each independently prognostic.

Clinical Impact: Transforming Treatment Decisions

Key insights from the study highlight HER2DX’s value in guiding treatment decisions for older individuals:

• Node-negative disease treated with trastuzumab alone: HER2DX identified a subgroup with excellent long-term outcomes, supporting the omission of chemotherapy in selected cases.
• HER2DX pCR score: Individuals with high pCR scores derived greater benefit from chemotherapy, particularly in terms of overall survival.
• Biological stratification: The assay’s component signatures (immune, luminal, proliferation) provided additive prognostic value and revealed substantial biological heterogeneity in this population.

These findings support the integration of HER2DX into clinical decision-making for older adults, enabling more personalized and less toxic treatment approaches.

Study Leaders Share Perspectives on HER2DX’s Role in Treating Older Patients
The study was led by Dr. Kazuki Nozawa (Nagoya City University) and co-senior authors Prof. Hiroji Iwata (Nagoya City University) and Dr. Aleix Prat, Co-founder and Chief Scientific Officer of REVEAL GENOMICS, Director of the Clínic Barcelona Comprehensive Cancer Center, and Professor of Medicine at the University of Barcelona.

“Older individuals with HER2-positive breast cancer are often excluded from biomarker-driven strategies,” explained Dr. Kazuki Nozawa. “This study demonstrates that HER2DX can provide meaningful prognostic information in this population. It’s time to incorporate this tool into routine clinical practice to better tailor treatments for the older population.”

“The RESPECT trial was designed to address a critical evidence gap in the treatment of older women with HER2-positive breast cancer,” noted Prof. Hiroji Iwata. “The integration of HER2DX into this trial provides a powerful example of how genomic tools can refine our understanding of risk. These results support the implementation of HER2DX to guide more personalized and less toxic treatment decisions.”

“This publication marks a significant milestone for HER2DX,” commented Patricia Villagrasa, CEO and Co-founder of REVEAL GENOMICS. “We are proud to contribute to the growing body of evidence supporting HER2DX as a transformative tool in precision oncology, especially for populations that have historically been overlooked in clinical research.”

About HER2DX
HER2DX is the world’s first diagnostic test formulated specifically for HER2+ breast cancer.
Marketed by REVEAL GENOMICS since January 2022, HER2DXis a standardized 27-gene expression test for patients with early-stage HER2+ breast cancer.

HER2DX is a prognostic, predictive assay based on clinical and genomic data. The test integrates clinical information (i.e. tumor size and nodal status) with biological information tracking immune response, luminal differentiation, tumor cell proliferation, and expression of the HER2 17q12-21 chromosomal amplicon, including the ERBB2 gene.

HER2DX predicts:

• Risk of relapse score (high vs. low): the risk of recurrence in patients with newly diagnosed HER2+ breast cancer.
• pCR likelihood score (high vs. medium vs. low): the likelihood of a patient responding to anti-HER2-based treatment before surgery.
• ERBB2 score (high vs. medium vs. low): the quantitative expression of ERBB2 mRNA across HER2-negative, HER2-low and HER2+ breast cancer.

About REVEAL GENOMICS
REVEAL GENOMICS, S.L. is a biotechnology start-up seeking to change the way biomarkers are used in oncology. It is focused on developing innovative diagnostic tools to define the best therapeutic options for patients with cancer. The company uses pioneering techniques, sophisticated computer applications, and machine learning to reveal new cancer research data.

REVEAL GENOMICS, S.L. is a spin-off of Hospital Clínic of Barcelona, IDIBAPS, University of Barcelona (U.B.), and Vall d’Hebron Institute of Oncology (VHIO).

REVEAL GENOMICS^® and HER2DX^® are registered trademarks of REVEAL GENOMICS, S.L.

Web: www.reveal-genomics.com.Twitter: @revealgenomics

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