Akademik Veri Yönetim Sistemi
II. INTERNATIONAL HEREDITARY CANCERS CONGRESS, Antalya, Türkiye, 5 - 08 Şubat 2026, ss.186-188, (Tam Metin Bildiri)
Clinicopathological Characteristics of Germline Pathogenic Variants in PALB2, RAD51C and RAD51D in Breast Cancer Patients: A Single-Center Experience Oğuzhan Yılmaz, Ebru Erzurumluoğlu Gökalp, Sevilhan Artan Department of Medical Genetics,Eskişehir Osmangazi University Faculty of Medicine,Eskişehir,Türkiye Introduction and Objective: Hereditary factors account for approximately 8% of breast cancer cases. While PALB2 germline pathogenic variants (GPV) are detected in roughly 1% of screened women—carrying a 7.2-fold relative risk and a 53% cumulative risk by age 80—prevalence data for RAD51C and RAD51D remain scarce. Although these genes are frequently linked to triple-negative breast cancer (TNBC), comprehensive data regarding other clinicopathological features like histological subtype and stage are limited. This study aims to characterize the clinicopathological profiles of patients with PALB2, RAD51C, or RAD51D GPVs identified via NGS at our center (2020–2025) and compare these findings with the current literature. Results: Among 487 breast cancer patients screened, germline pathogenic variants (GPVs) were identified in PALB2 (n=7; 1.4%), RAD51C (n=2), and RAD51D (n=2). The age at diagnosis for patients with PALB2 GPVs ranged from 35 to 67 years, with a median age of 51. Genotypically, the c.557dup (p.Asn186LysfsTer4) variant was identified in two unrelated patients, emerging as a recurrent mutation within this group. Analysis of histopathological data revealed a heterogeneous distribution; while the majority of patients presented with hormone receptor-positive (Luminal A and B) tumors, divergent phenotypes were observed among patients harboring the same genotypic alteration: one patient exhibited a HER2-positive phenotype, while the other presented with Triple-Negative Breast Cancer (TNBC). The most prominent shared clinical feature among RAD51C GPV carriers was an early age at diagnosis (41 and 45 years, respectively). Patients with RAD51D GPVs were of similar ages (54 and 52 years), and both were diagnosed with the Triple-Negative Breast Cancer (TNBC: ER-, PR-, HER2-) histological subtype. Discussion: Despite our limited cohort (n=11), these findings provide critical clinical insights. While international data report a median diagnosis age of 60–71 for RAD51C carriers, local studies suggest a younger onset of 50–55 years in Türkiye. Our notably earlier median of 43 may stem from ascertainment bias in high-risk clinical referrals or the early penetrance of specific variants like c.706-2A>G. Regarding RAD51D, the 100% correlation with the TNBC phenotype aligns with its established risk profile. Conversely, the PALB2 group exhibited significant phenotypic heterogeneity; although Luminal subtypes predominated, the presence of TNBC and HER2-positive cases reflects a broad spectrum similar to BRCA2. Finally, the recurrent c.557dup variant reinforces the likelihood of a population-specific founder mutation, highlighting the importance of geographic genetic signatures. Conclusion: Current guidelines classify PALB2, RAD51C, and RAD51D as moderate-to-high penetrance genes. Despite our limited cohort, these findings align with existing literature. The identification of population-specific variants, such as PALB2 c.557dup, underscores the clinical significance of geographic ancestry in genetic counseling. To establish the definitive prevalence of these genes in the Turkish population, larger multicenter studies are warranted. Keywords: PALB2, RAD51C, RAD51D, Breast Cancer