Ahmet DİNÇ, Hilal YAZICI, Hülya YAZICI
Turkish Journal of Oncology - 2025;40(4):332-348
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 recombination 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, highlighting 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 underrepresented 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-including PARP inhibitors, immunotherapy, and homologous recombination deficiency (HRD)-based regimens-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 dimensions 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.
