Biotechnology start-up Reveal Genomics detailed results of its DNADX assay in data presented at the San Antonio Breast Cancer Symposium 2023. DNADX is a novel machine learning-based approach that utilizes sequencing DNA data from tumor tissue or plasma circulating tumor DNA to identify clinically relevant phenotypic tumor features and classify breast cancer into four subtypes or clusters

Highlighting the trials’ exploration of the efficacy of the impact of T-DXd monotherapy and the combination of endocrine therapy with a CDK4/6 inhibitor, the results underscore the variability in patient response, emphasizing the critical role of precision diagnostics in cancer care, the company says.


The RELIEVE study, conducted by the Dana-Farber Cancer Institute (DFCI), analyzed plasma samples from patients with HER2+ and HER2- metastatic breast cancer receiving T-DXd monotherapy. DNADX subtypes, evaluated across 80 pre-treatment plasma samples, exhibited significant associations with time-to-next-treatment (TTNT) and overall survival (OS). Moreover, the DNADX HER2 signature demonstrated a significant association with TTNT, indicating its potential for predicting patient outcomes in the context of T-DXd monotherapy.

“The ability of the DNADX test to predict patient outcomes in blood and in the context of T-DXd monotherapy is remarkable,” says Sara Tolaney, MD, MPH, Chief of the Division of Breast Oncology at Dana-FarberCancer Institute. “This test should be further explored in pivotal clinical trials of T-DXd and other studies with targeted therapies, including antibody-drug conjugates.”

Further reading: Novel Biomarkers Help Decode Metastatic Breast Cancer


MEDSIR, a company specializing in the strategic design of independent clinical research, sponsored PARSIFAL phase II trial (NCT02491983), which randomized 486 patients with HR+/HER2- metastatic breast cancer to receive first-line palbociclib with either fulvestrant or letrozole; DNADX was evaluated in 122 pre-treatment plasma samples. 

The liquid biopsy-based DNADX subtypes exhibited a significant association with both progression-free survival (PFS) and (OS), revealing their potential to guide therapy and follow-up in patients with endocrine-sensitive HR+/HER2- advanced breast cancer.

“Prior to DNADX, no tool existed to identify patients whose tumors would progress to therapy in the first 12 months,” says Javier Cortés, MD, PhD, co-founder of MEDSIR, Head of the International Breast Cancer Center and investigator of the PARSIFAL trial. “This is important as we need new therapeutic approaches for these patients. Our study shows that the DNADX subtypes in plasma are strongly associated with prognosis in patients treated with first-line endocrine therapy and a CDK4/6 inhibitor.” 

These findings are consistent with validation studies of DNADX in this context published this year in Nature Communications.

Furthermore, DNADX subtypes demonstrated a positive interaction with the type of endocrine therapy in terms of PFS, suggesting a potential benefit of fulvestrant over letrozole in specific DNADX subtypes.

“The association of DNADX subtypes with fulvestrant benefit is intriguing, and suggests that phenotypic characterization of breast tumors using DNADX might allow us to identify the optimal endocrine treatment for each patient beyond ESR1 mutation,” says Antonio Llombart-Cussac, MD, PhD, co-founder of MEDSIR, head of the Medical Oncology Department at Hospital Arnau de Vilanova, and principal investigator of the PARSIFAL trial.

Funding and Recognition

“Our commitment lies in creating and advancing innovative genomic-based assays in oncology, such as our successful first product, HER2DX, for early-stage HER2+ breast cancer. Our forthcoming liquid biopsy-based assay, DNADX, marks our second product, slated for release in the short-term,” says Patricia Villagrasa, co-founder and CEO of Reveal Genomics. “We are pleased to announce that the Spanish Ministry of Science and Innovation has granted funding for the analytical and clinical validation of DNADX. This endorsement not only signifies the recognition of DNADX as an innovative tool, but also underscores its clinical utility.”