Hereditary breast, ovarian, pancreatic and prostate cancer syndrome: Multigene testing, multiomics, and risk management

Hereditary breast, ovarian, pancreas and prostate cancer (HBOC/HBOPC) syndromes remain a major global health concern, with BRCA1, BRCA2 and other high- or moderate-risk homologous recombi nation repair (HRR) gene variants driving a significant share of familial cancer risk. Beyond breast and ovarian sites, these mutations increase susceptibility to prostate, pancreatic, and other solid tumors, high lighting the syndromic nature of HBOPC. Advances in multigene panel testing (MPT), AI-supported variant classification, and polygenic risk scores (PRS) now enable more precise risk estimation, while functional reclassification and population-specific founder mutation mapping reduce uncertainty in un derrepresented groups. Emerging epigenetic and non-coding RNA biomarkers further strengthen early detection and treatment stratification. However, large-scale validation is still needed to translate these tools into equitable care. Risk-reducing surgeries, tailored surveillance, and targeted therapies—includ ing PARP inhibitors, immunotherapy, and homologous recombination deficiency (HRD)-based regi mens—have transformed management but require equitable access and culturally sensitive counseling to address psychosocial barriers and family communication challenges. Real-world data (RWD) and cross border variant databases are essential to bridge gaps between guidelines and practice, especially where founder effects and mosaicism complicate standard criteria. This review integrates current evidence on the genetic and molecular foundations, organ-specific management, evolving therapies, and ethical di mensions of HBOPC care. By combining multidisciplinary insights with AI, functional analyses, and real-world implementation strategies, this review highlights how next-generation precision oncology can deliver equitable, high-quality, and locally adapted prevention and treatment for families worldwide.