학술논문
Risk of metastasis in BRCA2 carriers diagnosed with triple-negative breast cancer.
Document Type
Academic Journal
Author
Moreno M; Graduate Program of A.C. Camargo Cancer Center, São Paulo, Brazil.; Medicine Course and Biomedical Sciences, Federal University of Fronteira Sul, Chapecó, Santa Catarina, Brazil.; Oliveira JS; Graduate Program of A.C. Camargo Cancer Center, São Paulo, Brazil.; Brianese RC; Clinical and Functional Genomics Group, CIPE, A.C. Camargo Cancer Center, São Paulo, Brazil.; de Castro DG; Department of Radiation Oncology, A.C. Camargo Cancer Center, São Paulo, Brazil.; Sanches SM; Department of Medical Oncology, A.C. Camargo Cancer Center, São Paulo, Brazil.; Torrezan GT; Clinical and Functional Genomics Group, CIPE, A.C. Camargo Cancer Center, São Paulo, Brazil.; National Institute of Science and Technology in Oncogenomics and Therapeutic Innovation (INCITO), São Paulo, Brazil.; Santiago KM; Clinical and Functional Genomics Group, CIPE, A.C. Camargo Cancer Center, São Paulo, Brazil.; De Brot M; Department of Anatomic Pathology, A.C. Camargo Cancer Center, São Paulo, Brazil.; Cordeiro de Lima VC; Department of Medical Oncology, A.C. Camargo Cancer Center, São Paulo, Brazil.; Baroni Alves Makdissi F; Department of Breast Surgery, A.C. Camargo Cancer Center, São Paulo, Brazil.; Casali Da Rocha JC; Department of Oncogenetics, A.C. Camargo Cancer Center, São Paulo, Brazil.; Calsavara VF; Biostatistics and Bioinformatics Research Center, Cedars-Sinai Medical Center, Los Angeles, California, USA.; Carraro DM; Clinical and Functional Genomics Group, CIPE, A.C. Camargo Cancer Center, São Paulo, Brazil.; National Institute of Science and Technology in Oncogenomics and Therapeutic Innovation (INCITO), São Paulo, Brazil.
Source
Publisher: John Wiley & Sons Ltd Country of Publication: United States NLM ID: 101595310 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2045-7634 (Electronic) Linking ISSN: 20457634 NLM ISO Abbreviation: Cancer Med Subsets: MEDLINE
Subject
Language
English
Abstract
Background: Triple-negative breast cancer (TNBC) is the neoplasia most associated with BRCA1 germline pathogenic variants (PV) and is more likely to develop metastases than the other breast cancer (BC) subtypes, mainly in the lungs and the central nervous system (CNS). Recently, BRCA2 carriers were shown to have a higher risk for developing CNS metastases. However, the patterns of recurrence and metastases of BRCA2 carriers with TNBC are unknown.
Methods: TNBC patient data attending the A.C. Camargo Cancer Center, from 1998 through 2020, were verified either by medical records or by BRCA1/2 genetic testing carried out. Multivariable logistic regression models were fit to the data to assess the independent factors for bone and CNS metastases. Adjustment was done using all independent variables with p < 0.2 in the univariable Cox model to describe the relationship between the independent variables until time of death.
Results: A total of 388 TNBC patients were evaluated. We identified PV in BRCA1/2 genes in 21% (82/388), being 17.7% (69/388) in BRCA1 and only 3.3% (13/388) in BRCA2. A total of 120 patients (31%) developed distant metastases. Bone or CNS metastases were observed in 40% and 60% of BRCA2 PV carriers (p = 0.155), respectively. The BRCA2 carriers tended to have a higher likelihood of developing bone metastases (OR, 4.06; 95% CI, 0.82-20.01; p = 0.085), when compared to BRCA1 carriers (OR, 0.6; 95% CI, 0.12-2.87; p = 0.528). BRCA2 carriers had an OR of 1.75 (95% CI, 0.33-9.14; p = 0.503) for CNS metastasis development, while BRCA1 carriers had an OR of 0.72 (95% CI, 0.23-2.23; p = 0.574).
Conclusions: Patients with TNBC and PV in the BRCA2 gene had higher frequencies of secondary bone involvement and CNS in the course of the disease. However, the BRCA2 PV did not represent an independent outcome predictor of metastases and overall survival. Efforts to increase the number of BRCA2 carriers among TNBC patients are crucial for determining their risk of developing bone and CNS metastases compared to BRCA2 noncarriers.
(© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
Methods: TNBC patient data attending the A.C. Camargo Cancer Center, from 1998 through 2020, were verified either by medical records or by BRCA1/2 genetic testing carried out. Multivariable logistic regression models were fit to the data to assess the independent factors for bone and CNS metastases. Adjustment was done using all independent variables with p < 0.2 in the univariable Cox model to describe the relationship between the independent variables until time of death.
Results: A total of 388 TNBC patients were evaluated. We identified PV in BRCA1/2 genes in 21% (82/388), being 17.7% (69/388) in BRCA1 and only 3.3% (13/388) in BRCA2. A total of 120 patients (31%) developed distant metastases. Bone or CNS metastases were observed in 40% and 60% of BRCA2 PV carriers (p = 0.155), respectively. The BRCA2 carriers tended to have a higher likelihood of developing bone metastases (OR, 4.06; 95% CI, 0.82-20.01; p = 0.085), when compared to BRCA1 carriers (OR, 0.6; 95% CI, 0.12-2.87; p = 0.528). BRCA2 carriers had an OR of 1.75 (95% CI, 0.33-9.14; p = 0.503) for CNS metastasis development, while BRCA1 carriers had an OR of 0.72 (95% CI, 0.23-2.23; p = 0.574).
Conclusions: Patients with TNBC and PV in the BRCA2 gene had higher frequencies of secondary bone involvement and CNS in the course of the disease. However, the BRCA2 PV did not represent an independent outcome predictor of metastases and overall survival. Efforts to increase the number of BRCA2 carriers among TNBC patients are crucial for determining their risk of developing bone and CNS metastases compared to BRCA2 noncarriers.
(© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)