The Germans Trias Research Institute and ICO Badalona describe genomic alterations that may help predict treatment response in an aggressive type of breast cancer

• Researchers have identified genomic alterations associated with treatment response in HER2-positive breast cancer.
• Understanding the factors that influence the benefit of treatments in HER2-positive breast cancer will help cure more patients and with reduced toxicity.

The Molecular and Translational Pathology Research Group at the Germans Trias i Pujol Research Institute and the Pathology Department of the Hospital, in collaboration with the Medical Oncology Department at Institut Català d'Oncologia - Badalona (ICO-Badalona), have described a set of molecular alterations that may help predict treatment response in a specific type of breast cancer.

This is a subtype of the disease characterised by HER2 amplification, which, although not the most common form, requires targeted therapies and still presents many challenges in improving cure rates and reducing treatment toxicity.

To address this, the multidisciplinary research group, part of the CARE Program (Translational Program in Cancer Research), conducted a study analysing tumour DNA from patients diagnosed with HER2-positive breast cancer, both before and after standard therapy. From this observation, and by comparing tumours that responded to treatment with those that did not respond well, the study was able to identify a series of molecular alterations in these tumours. "We observed that certain genes are associated with a poorer treatment response and, additionally, we found one that is frequently altered and could help predict that response", explains Pedro Luis Fernández, leader of the research group and head of the Pathology Department at Germans Trias Hospital.

Specifically, Fernández refers to the TP53 gene, which is well known in oncology but had not previously been clearly linked to treatment response in the context of HER2-positive breast cancer. This discovery -recently published in Modern Pathology, the leading journal in the field of Anatomical Pathology- leads the researchers to believe that TP53 analysis should be included among the essential biomarker tests performed before starting treatment for HER2-positive breast cancer, in order to help predict the response.

"If we suspect from the outset that the tumour is unlikely to respond well due to a TP53 mutation, we could avoid ineffective or unnecessary treatments and save time by opting for alternatives", illustrates Fernández, who also highlights the simplicity and speed of analysing this gene from the start, as it can be easily incorporated as an additional biomarker.

Laura Pons, also a member of the research group and first author of the study, underscores the qualitative and quantitative relevance of the work, which was funded by Instituto de Salud Carlos III and supported by Fundació La Marató de TV3. "It is a very important genomic sequencing study in the field of neoadjuvant therapy, based on high-quality samples that we collected and analysed using specialised technology, but also involving a significant investment of time", she notes. The more than 60 cases analysed correspond to women followed at the hospital between 2016 and 2022.

On average, the Germans Trias treats around thirty new cases of HER2-positive breast cancer each year, half of which do not respond fully to therapy. Pons also expresses the intention to recruit cases from other hospitals for this analytical work, "in order to further demonstrate what we have already shown in these more than 60 cases". In this regard, both Fernández and Pons hope that the genetic alterations described may help the scientific community develop useful models to provide more accurate diagnoses and new treatments or therapeutic strategies that improve survival in these patients.

Reference

Pons L, Hernandez L, Urbizu A, Arnaldo L, Rodriguez-Martinez P, Sanz C, Muñoz-Mármol AM, Fernandez E, Felip E, Quiroga V, Margelí M, Fernandez PL. Molecular landscape, genomic shift, and prediction in the neoadjuvant setting of human epidermal growth factor receptor 2-positive breast cancer. Mod Pathol. 2025 Sep;38(9):100787. DOI: 10.1016/j.modpat.2025.100787.