Rome, March 17, 2026 – A significant breakthrough in breast cancer treatment has been achieved, according to research published today in the prestigious scientific journal Nature. Italian researchers have identified specific genetic mutations that influence how breast tumors evolve and develop resistance to therapies, potentially paving the way for more effective, personalized treatment plans. This discovery offers new hope for patients facing treatment challenges and underscores the importance of genetic testing in cancer care.
Understanding Resistance Through Genetic Profiling
The study, conducted by researchers at the European Institute of Oncology – including Emanuela Ferraro, Antonio Marra, and Luca Boscolo Bielo – revealed that inherited genetic mutations play a key role in determining a tumor’s ability to become resistant to medication. Researchers not only pinpointed the molecular profile that drives drug resistance in breast cancers but also gained insights into how to delay that resistance, ultimately improving treatment outcomes.
“We have established a model for predicting the trajectories of drug resistance based on the configuration of the patient’s genome, demonstrating once again the fundamental importance of knowing the genetic profile before treatment, to choose the best possible therapy for each person,” explained Antonio Marra.
The Role of Genetic Mutations in Drug Resistance
Historically, the genetic basis of drug resistance in breast cancer has been poorly understood. While both inherited (germline) and non-inherited (somatic) mutations contribute to tumor evolution, the interplay between these genetic alterations and the development of drug resistance remained unclear. The new study, which analyzed clinical and genomic data from over 5,800 patients, sheds light on this complex relationship.
Researchers discovered that certain inherited genetic mutations, such as those in the BRCA2 gene, predispose tumors to evolve and become resistant to treatment.
Instability in DNA: A Key Factor
“We have demonstrated that breast tumors with a germline mutation in BRCA2 have a strong predisposition to loss of the RB1 gene, which renders DNA unstable. This creates a ‘double hit’ mechanism: an existing genetic vulnerability due to the inherited mutation, combined with DNA instability, promotes the development of resistance during therapy. Standard treatments, such as the combination of endocrine therapy and CDK4/6 inhibitors, are less effective against these tumors,” explained Emanuela Ferraro.
“But,” she continued, “we have observed that in experimental models and clinical data, PARP inhibitors appear to work better than CDK4/6 inhibitors in patients with BRCA2, opening up exceptionally interesting new perspectives for the apply of these drugs as a first-line treatment. In fact, a study has already been initiated based on these results.”
PARP Inhibitors: A New Approach to Enhance Effectiveness
“PARP inhibitors have been used for several years with excellent results against HER2-negative and BRCA1/2-mutated breast cancer, both metastatic and early-stage. However, these excellent drugs have only been used as a second-line treatment, i.e., when the first drug has stopped being effective. Our new data indicate that prioritizing PARP inhibitors in patients carrying a BRCA2 mutation can intercept the trajectories of RB1 gene loss and thus delay resistance to drugs,” continued Antonio Marra.
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