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.

Barcelona, Spain.  REVEAL GENOMICS, S.L., a Barcelona-based biotechnology company seeking to revolutionize precision oncology through biomarker innovation, today announced the upcoming 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 70–80years 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.”