Divergent Prognostic Impact of Germline <i>BRCA1</i> and <i>BRCA2</i> Variants in Non-Metastatic Breast Cancer: A Real-World Cohort Study
CANCERS, cilt.18, sa.19, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 18 Sayı: 19
- Basım Tarihi: 2026
- Doi Numarası: 10.3390/cancers18193073
- Dergi Adı: CANCERS
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, CINAHL, EMBASE, Academic Search Ultimate (EBSCO), Natural Science Collection (ProQuest), Biological Science Database (ProQuest), Biomedical Reference Collection: Corporate Edition (EBSCO)
- Trakya Üniversitesi Adresli: Evet
Özet
Background: Germline pathogenic variants in BRCA1 and BRCA2 are established contributors to hereditary breast cancer, yet their separate prognostic effects in non-metastatic disease remain uncertain because they are frequently analyzed as a single group. Methods: We retrospectively evaluated 360 patients with stage I-III invasive breast cancer who underwent germline genetic testing. Patients were categorized as BRCA-negative (n = 281), BRCA1-positive (n = 43), or BRCA2-positive (n = 36). Disease-free survival (DFS) and overall survival (OS) were analyzed using Kaplan-Meier methods and Cox proportional hazards models with adjustment for molecular subtype and clinicopathological variables. Results: During follow-up, 76 DFS events and 27 deaths were observed. BRCA2 positivity was independently associated with worse DFS (hazard ratio [HR] 2.13, 95% confidence interval [CI] 1.14-3.98; p = 0.017), whereas BRCA1 positivity showed an association with improved OS (HR 0.08, 95% CI 0.01-0.51; p = 0.007). The OS finding should be interpreted cautiously because of the limited number of death events and the risk of model instability. Conclusions: Germline BRCA1 and BRCA2 variants may have divergent prognostic implications in non-metastatic breast cancer and should not be treated as a single homogeneous prognostic entity. Separate evaluation of these variants may improve risk stratification and support more individualized patient management, although validation in larger cohorts is warranted.