- A study led by the IIBM, together with Hospital 12 de Octubre, analyzes why some patients have a poor tolerance of a key treatment for advanced breast cancer less well than others
A team of researchers from the Pharmacogenomics and Tumor Biomarkers Group, led by Cristina Rodríguez-Antona at the Instituto de Investigaciones Biomédicas Sols-Morreale (IIBM), CSIC-UAM, in collaboration with the Medical Oncology Department at Hospital 12 de Octubre, the SOLTI group, and 26 Spanish hospitals, has investigated the factors that may explain the occurrence of adverse events in patients with advanced breast cancer treated with trastuzumab deruxtecan. The study results have been published in the journal ESMO Open.
Trastuzumab deruxtecan is an innovative treatment that combines an antibody targeting tumor cells with a chemotherapy drug, allowing cancer to be attacked more specifically. It has shown high efficacy in advanced breast cancer, especially in HER2-positive tumors or tumors with low HER2 expression. However, approximately 20% of patients must discontinue treatment due to side effects.
This work is part of the PROCURE Project, a multicenter study involving 26 Spanish hospitals and the SOLTI group, which investigates trastuzumab deruxtecan toxicity in patients with HER2-positive advanced breast cancer. The initiative integrates clinical and genetic data to advance more personalized oncology approaches.
The researchers analyzed 292 patients treated between 2022 and 2024 to determine whether genetic variations in the UGT1A1 gene could explain differences in toxicity. This gene had previously been associated with an increased risk of adverse events in other similar treatments.
The results show that, overall, genetic variants in the UGT1A1 gene do not predict which patients will develop greater toxicity with trastuzumab deruxtecan. No significant association was found with most adverse events, including pneumonitis, a lung inflammation that represents one of the most relevant side effects of this treatment.
However, patients carrying a specific genotype (the *28/*28 genotype) showed a trend toward higher rates of neutropenia and gastrointestinal toxicity. Interestingly, these same patients also remained on treatment for a longer period of time.
Overall, the findings highlight the complexity of predicting trastuzumab deruxtecan toxicity and the need to identify new biomarkers that can better anticipate which patients are at greater risk of adverse events, thereby advancing more personalized oncology.
The study also underscores the importance of collaboration between research centers and hospitals — involving 26 Spanish hospitals — as well as the commitment of the patients, whose contribution was essential to carrying out this work.