Divergent Prognostic Impact of Germline BRCA1 and BRCA2 Variants in Non-Metastatic Breast Cancer: A Real-World Cohort Study.
5 affiliations
- 1Division of Medical Oncology, Department of Internal Medicine, Trakya University School of Medicine, 22130 Edirne, Turkey.
- 2Department of Radiation Oncology, Trakya University School of Medicine, 22130 Edirne, Turkey.
- 3Department of Biostatistics, Trakya University School of Medicine, 22130 Edirne, Turkey.
- 4Department of Medical Genetics, Trakya University School of Medicine, 22130 Edirne, Turkey.
- 5Trakya University School of Medicine, 22130 Edirne, Turkey.
Abstract
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.
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BibTeX
@article{bayrakci2026divergent,
title = {{Divergent Prognostic Impact of Germline BRCA1 and BRCA2 Variants in Non-Metastatic Breast Cancer: A Real-World Cohort Study.}},
author = {Ismail Bayrakci and Rusen Cosar and Necdet Sut and Hakan Gurkan and Omer Faruk Cetinkaya and Eylul Senodeyici and Didem Divriklioglu and Gizem Bakir Kahveci and Ahmet Kucukarda and Muhammet Bekir Hacioglu and Bulent Erdogan and Sernaz Topaloglu},
journal = {Cancers},
year = {2026},
month = sep,
doi = {10.3390/cancers18193073},
url = {https://europepmc.org/article/MED/42882768},
note = {CC BY},
}
RIS
TY - JOUR
TI - Divergent Prognostic Impact of Germline BRCA1 and BRCA2 Variants in Non-Metastatic Breast Cancer: A Real-World Cohort Study.
AU - Ismail Bayrakci
AU - Rusen Cosar
AU - Necdet Sut
AU - Hakan Gurkan
AU - Omer Faruk Cetinkaya
AU - Eylul Senodeyici
AU - Didem Divriklioglu
AU - Gizem Bakir Kahveci
AU - Ahmet Kucukarda
AU - Muhammet Bekir Hacioglu
AU - Bulent Erdogan
AU - Sernaz Topaloglu
PY - 2026
DA - 2026/09/22
JO - Cancers
DO - 10.3390/cancers18193073
UR - https://europepmc.org/article/MED/42882768
AB - 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.
SN - 2072-6694
ER -