SABCS 2025: REVEAL GENOMICS Presents Major Advance in Predicting Brain Metastasis in HER2+ Breast Cancer

The new HER2DX central nervous system (CNS) progression score predicts risk of brain progression in advanced HER2+ breast cancer, addressing a major unmet need in identifying patients at the highest risk of CNS involvement. During SABCS 2025, the company presents a total of 7 studies with 1,300 tumor samples analyzed, covering HER2-positive, ER-negative, and triple-negative breast cancer (TNBC), representing one of the largest and most comprehensive genomic data contributions to the symposium. New clinical evidence includes superior pCR prediction compared with TILs, demonstration of real-time genomic testing feasibility in an international trial, and validation of RNA-based ERBB2 assessment to accelerate clinical decision-making.

REVEAL GENOMICS, S.L., a Barcelona-based biotechnology company focused on advancing precision oncology through biomarker innovation, announced today the presentation of seven studies at the upcoming San Antonio Breast Cancer Symposium (SABCS) 2025, held December 9–12 in San Antonio, Texas.

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These abstracts showcase the growing clinical utility and innovation of the company’s proprietary RNA platform and underscore REVEAL GENOMICS’ commitment to improving outcomes for individuals with breast cancer.

Across all studies, REVEAL GENOMICS and its collaborators analyzed more than 1,300 tumor samples from individuals with HER2-positive, ER-negative, and triple-negative breast cancer—one of the most extensive genomic contributions to SABCS 2025.

Seven independent studies validate the performance and clinical impact of REVEAL GENOMICS’ precision oncology platform

• New HER2DX Genomic Scores: Predicting Overall Survival and Brain Progression in Advanced HER2+ Breast Cancer

REVEAL GENOMICS presents two new analyses in a cohort of 215 individuals with advanced HER2-positive breast cancer, including 93 cases from Spain and 122 from Poland. The studies show that the HER2DX ERBB2 score, together with two newly developed genomic scores, independently predicts overall survival and the risk of brain progression in individuals treated with first-line therapy and in subsequent treatment settings.

These findings are particularly relevant in a landscape where multiple therapeutic options now exist, each with different levels of efficacy and tolerability. CNS progression remains a major unmet need, and until now no biomarker has been available to identify those at highest risk.

The newly developed HER2DX CNS Progression Score demonstrated a strong ability to stratify risk. In the Polish validation cohort, the 3-year cumulative incidence of CNS progression was 39.2% in the high-risk group, 13% in the intermediate-risk group, and 4.3% in the low-risk group.

Taken together, these results highlight the potential of HER2DX genomic scores—including the new CNS Progression Score—to guide treatment selection, personalize CNS surveillance, and ultimately improve outcomes for individuals with advanced HER2-positive breast cancer.

• Operational Feasibility of HER2DX in the DEFINITIVE Trial

The DEFINITIVE trial (NCT06446882) is an ongoing, international, multicenter, randomized prospective clinical trial across Europe and Israel. Funded by the European Union, it has been designed to evaluate the impact of HER2DX-guided treatment in stage II-III HER2-positive breast cancer. The poster presented at SABCS 2025 shows real-time operational insights from the first 122 patients screened. HER2DX testing was successfully completed in 115 cases (success rate 94.3%). The median turnaround time from sample reception to result was 7 working days, confirming the feasibility of rapid, centralized genomic testing. These results support the integration of genomic classifiers into real-time treatment decision-making in prospective clinical trials.

• HER2DX Genomic Test: SABCS 2025 & Newly Published Data

REVEAL GENOMICS also presents new data showing that HER2DX scores reflect pathological features from both the tumor and its immune microenvironment. However, no clinical-pathological variable could fully capture the information contained in the HER2DX scores. Most importantly, the HER2DX pCR score emerged as the only variable independently associated with pathologic complete response (pCR), even after adjusting for tumor-infiltrating lymphocytes (TILs). Notably, TILs were no longer predictive once the HER2DX pCR score was included in the analysis. These findings were recently published in Clinical Cancer Research.

• HER2DX pCR Score vs. TILs in the COMPASSHER2 pCR Trial

A proffered paper (GS1-04) evaluated TILs in the COMPASSHER2 pCR trial from ECOG-ACRIN, comparing their performance with the HER2DX pCR score in 569 patients. HER2DX was assessed as a secondary aim within a pre-specified, prospectively planned analysis embedded in COMPASSHER2 pCR (EA1181; NCT04266249), a large multicenter phase II trial evaluating neoadjuvant THP in more than 2,000 patients with stage II–III HER2-positive breast cancer. The results are fully consistent with the previous work developed: although TILs are associated with pCR, their predictive value disappears once the HER2DX pCR score is included in the model. This further reinforces the superior predictive ability of the HER2DX pCR score compared with TILs alone for identifying patients most likely to achieve a pCR.

• Prospective Evaluation of ERBB2 mRNA Score in ER-Negative Breast Cancer

A prospective pilot study evaluated whether the ERBB2 mRNA score—integrated into the HER2DX and TNBCDX assays—could streamline HER2 assessment in ER-negative breast cancer. Both assays were run blinded to HER2 status using their standard RNA-based platform. Based on the ERBB2 mRNA level, samples were automatically routed to the appropriate assay: ERBB2-low tumors generated a TNBCDX output, whereas ERBB2-medium/high tumors generated a HER2DX output. In parallel, all tumors underwent routine HER2 testing by IHC/ISH.

The ERBB2 mRNA score demonstrated perfect concordance with standard HER2 classification, correctly identifying every HER2-positive and HER2-negative case. These findings support RNA-based HER2 assessment as an accurate, rapid, and operationally simple approach that can help accelerate neoadjuvant decision-making in ER-negative disease.

• Independent Validation of TNBCDX in Early Triple-Negative Breast Cancer

A new independent validation study in 164 patients from two Spanish academic centers confirms that the TNBCDX 15-gene assay—used to generate both the pCR score and the risk score—accurately predicts pCR and recurrence risk in early-stage TNBC, irrespective of anthracycline or pembrolizumab use. These results build on the Annals of Oncology publication, where TNBCDX was originally developed and validated in 527 patients across three prospective neoadjuvant studies. In that analysis, the TNBCDX pCR score was significantly associated with pCR, and the TNBCDX risk score consistently predicted long-term outcomes including distant disease-free survival, and overall survival.

Together, the original 527-patient dataset and this new independent 164-patient cohort provide converging evidence that TNBCDX is a robust and reproducible tool for refining risk stratification and supporting more individualized systemic therapy decisions in early-stage TNBC.

Company Leadership Highlights the Impact and Vision Behind These Breakthroughs
The leadership of REVEAL GENOMICS highlights the importance of the SABCS 2025 findings, emphasizing their impact on advancing precision oncology and supporting clinicians and patients.

Prof. Aleix Prat, MD, PhD, Co-founder and CSO, remarks: "These results reflect years of collaborative research and our commitment to translating genomic science into real-world benefits for patients. We are proud to see our tools making a tangible difference in breast cancer care. The breadth of data presented at SABCS 2025 demonstrates the versatility and clinical impact of our genomic platforms. We are excited to continue advancing precision oncology through robust science and innovation."

Dr Patricia Villagrasa, Co-founder and CEO, adds: "Our mission is to empower clinicians and patients with the best possible information for treatment decisions. The progress showcased at SABCS 2025 is a clear reflection of our team’s dedication and the trust placed in us by the oncology community."

About REVEAL GENOMICS^®️
REVEAL GENOMICS, S.L. is a biotechnology start-up seeking to change the way biomarkers are used in oncology.It is dedicated to developing and delivering innovative genomic solutions that empower clinicians and patients with actionable insights for precision cancer care. The company’s HER2DX and TNBCDX platforms are at the forefront of personalized medicine, enabling more accurate risk assessment, treatment selection, and improved patient outcomes.

Its focus resides 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 company of Hospital Clínic of Barcelona, IDIBAPS, the University of Barcelona (U.B.), and the 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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