HER2DX: First genomic test for personalized HER2+ breast cancer treatments

January 25, 2022

·       HER2DX is the world's first diagnostic test formulated specifically for HER2-positive (HER2+) breast cancer.

·       HER2DX analyzes RNA on 27 genes to predict survival outcomes and the likelihood that patients will respond to treatment.

·       HER2DX has been validated on more than 1,000 patients, the results being published in The Lancet EBioMedicine.

·       The test was developed thanks to a partnership between Spanish, Italian and US researchers and will be marketed by REVEAL GENOMICS, a spin-off of Hospital Clínic de Barcelona, the August Pi i Sunyer Biomedical Research Institute (IDIBAPS), the University of Barcelona (UB) and the Vall d’Hebron Institute of Oncology (VHIO).

Barcelona, January 25, 2022. Researchers from Hospital Clínic-IDIBAPS-UB, VHIO, University of Padua (Italy) and REVEAL GENOMICS have developed and validated HER2DX, a genomic test that uses the clinical details and genomic data of early-stage HER2+ patients to predict their prognosis and probability to respond to drug therapies prior to undergoing surgery. HER2DX is the world's first genomic test intended for patients with HER2+ breast cancer.

The reliability of the HER2DX test has been established in a study coordinated by Dr. Aleix Prat, head of the Medical Oncology Department at Hospital Clínic, member of the IDIBAPS Translational Genomics and Solid Tumor Targeted Therapy Group, Professor at UB and co-founder of REVEAL GENOMICS in cooperation with a research group of the University of Padova headed by Prof. Pierfranco Conte and Prof. Valentina Guarneri; the study has been published in The Lancet EBioMedicine.

HER2+ breast cancer accounts for 20% of all diagnosed breast tumors. This represents more than 390,000 cases are diagnosed worldwide each year, which would mean that, on average, three women are diagnosed with HER2+ breast cancer every four minutes. Over more than five years, research undertaken at the laboratory headed by Dr. Prat and Dr. Charles M. Perou, researcher at the University of North Carolina at Chapel Hill (USA), co-founder of REVEAL GENOMICS and co-author of the study, has led to the discovery of the biological heterogeneity of HER2+ breast cancer, making it possible to identify patients with different responses to treatment and varying probabilities of recurrence after being diagnosed with breast cancer. “Our initial aim was to use the biological knowledge that we had accumulated with regard to the disease to help oncologists and patients make the best treatment decisions. To do this, we integrated and validated the clinical and genomic data of more than 1,000 patients. The effort was worthwhile and we can now say that HER2DX test is an innovative tool that allows us to predict the behavior of each patient’s tumor with greater reliability compared to the information available without the test”, says Dr. Prat.

Prior to this, clinicians had no tools other than tumor size and axillary node involvement to predict the risk of recurrence or the probability of survival. “Over the past 10 years major progress has been made in the treatment of HER2+ breast cancer. The issue now is that some patients receive more treatment than they need while, for some other patients, the treatment we give is not sufficient to cure their cancer. The problem is that critical therapeutic decisions, such as the amount or type of chemotherapy or the amount or duration of HER2 treatment, did not take the biological heterogeneity of the disease into account”, says Prof. Conte, co-author of the study.

A test that combines clinical and genomic variables to benefit patients

HER2DX measures the RNA levels of 27 genes, using an intelligent analytical software to divide patients into high and low risk groups, by giving them a score from 0 to 100. It does this by capturing the four crucial biological processes of HER2+ breast cancer: 1) activation of the immune system within the tumor, 2) the differentiated status of tumor cells, 3) the proliferation status of the tumor, and 4) the expression of the HER2 gene and several neighboring genes on chromosome 17. The information provided by the 27 genes, along with tumor size and axillary node involvement, is used to supply two types of clinical information: 1) patient prognosis and 2) tumor sensitivity to chemotherapy and HER2 treatments given prior to tumor surgery. The reliability of each of these indicators was validated via a range of tests on multiple cohorts totaling more than 1,000 patients.

"It is not new that genomics provides us with a lot of data. But now, for the first time, in the context of HER2+ breast cancer, we have been able to develop a tool that brings all this information into clinical practice, to make treatment as personalized and precise as possible. Tests, such as HER2DX, that predict the response to a given drug and provide information on biological aspects of the disease will be the most helpful for oncologists in the future. It will allow them to go deeper and understand each specific case," explained Dr. Ana Vivancos, head of the Cancer Genomics Group at VHIO and co-founder of REVEAL GENOMICS.  

T.J., a patient with early-stage HER2+ breast cancer who underwent chemotherapy and anti-HER2 treatment prior to surgery at Hospital Clínic, says: “After surgery we saw that the treatment went well, but residual tumor cells were found. Nevertheless, the new diagnostic test showed that my illness was low-risk and that the treatment I am receving now should be enough to give excellent long-term results, which is very reassuring for me”.

Another patient, E.L., who was diagnosed with high-risk HER2+ breast cancer using HER2DX, is currently undergoing chemotherapy with two anti-HER2 drugs prior to surgery: “In my case, the test confirmed that my cancer was high risk, but also indicated that my tumor has very high levels of the HER2 gene. Thanks to these findings, the clinical team indicated more intensive treatment than would be normal”.

The world's first specialized test for HER2+ breast cancer

HER2DX is now available and commercialized by REVEAL GENOMICS, the spin-off whose founders, in addition to Dr. Prat, Dr. Perou and Dr. Vivancos are Dr. Joel S. Parker, from the University of North Carolina at Chapel Hill (USA), and Dr. Patricia Villagrasa-González, CEO of the company. “Just one year after setting up REVEAL GENOMICS, we are happy to launch the company's first precision oncology test. We are convinced that HER2DX will provide oncologists and patients with the information they need to make the best therapeutic decisions”, says Dr. Villagrasa-González. HER2DX has been made possible thanks to a partnership between REVEAL GENOMICS and the Hospital Clínic of Barcelona Biomedical Diagnostic Center (CDB), headed by Dr. Aurea Mira, who, with her team, has also co-authored the study: “It is a great leap in technological and scientific innovation that, with the expertise of the CDB, is going to be available in record time for the benefit of patients with breast cancer", says Dr. Mira.


Development and validation of the new HER2DX assay for predicting pathological response and survival outcome in early-stage HER2-positive breast cancer
Aleix Prat, Valentina Guarneri, Tomás Pascual, Fara Brasó-Maristany, Esther Sanfeliu, Laia Paré, Francesco Schettini, Débora Martínez, Pedro Jares, Gaia Griguolo, Maria Vittoria Dieci, Javier Cortés, Antonio Llombart-Cussac, Benedetta Conte, Mercedes Marín-Aguilera, Nuria Chic, Joan Anton Puig-Butillé, Antonio Martínez, Patricia Galván, Yi-Hsuan Tsai, Blanca González-Farré, Aurea Mira, Ana Vivancos, Patricia Villagrasa, Joel S. Parker, Pierfranco Conte, Charles M. Perou.