PREDICTIVE BRCA GENETIC TESTING IN ITALIAN PATIENTS WITH BREAST CANCER: A POSITION PAPER OF ITALIAN SCIENTIFIC SOCIETIES [Italian Association of Medical Oncology(AIOM); Italian Association of Radiotherapy and Clinical Oncology (AIRO); Italian National Association of Breast Surgeons (ANISC); Italian Society of Pathological Anatomy and Diagnostic Cytology (SIAPeC-IAP); Italian Society of Surgical Oncology (SICO); Italian Society of Human Genetic (SIGU); Italian Society of General Practice (SIMG); Italian Society of Medical and Interventional Radiology (SIRM)]

The introduction of Poly (ADP-ribose) Polymerase (PARP) inhibitors in both metastatic and early-stage breast cancer (BC) treatment has led to the emergence of Mainstreaming Cancer Genetics (MCG) as a new approach to genetic counselling, predictive of therapy outcomes. Therefore, the BRCA testing criteria for therapeutic purposes require further implementation. This position paper outlines the Italian indications for predictive genetic testing, approved by a multidisciplinary Expert Panel representing major scientific societies involved in BC treatment in Italy. We utilized the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, and framed clinical questions as population, intervention, comparison and outcome (PICO). The final recommendations were determined through a voting process, covering key topics such as eligibility criteria for onco-genetic counselling, the role of contralateral prophylactic mastectomy (CPM) in patients harboring BRCA1/2 germline pathogenic variants (gPV), and the positioning of predictive BRCA1/2 test. As results, the Expert Panel defined three distinct patient groups eligible for onco-genetic counselling, based on the a priori likelihood of carrying a gPV and the purpose of testing (predictive vs preventive). A conditional recommendation in favor of CPM in patients with a history of surgically treated BC and a BRCA gPV was suggested. Finally, a multidisciplinary pathway for BRCA testing was proposed, for patients with triple negative and hormone receptor-positive (HR+)/HER2-negative (HER2−) BC. In conclusion, the predictive BRCA testing inside the onco-genetic framework marks an important step-forward in BC management. However, the integration of somatic testing, digital pathology, and artificial intelligence-driven models could refine patient selection for tailored treatments.