Cancer Medicine (Aug 2023)

Risk of metastasis in BRCA2 carriers diagnosed with triple‐negative breast cancer

  • Marcelo Moreno,
  • Júlia Salles Oliveira,
  • Rafael Canfield Brianese,
  • Douglas Guedes deCastro,
  • Solange Moraes Sanches,
  • Giovana Tardin Torrezan,
  • Karina Miranda Santiago,
  • Marina De Brot,
  • Vladmir Claudio Cordeiro de Lima,
  • Fabiana Baroni Alves Makdissi,
  • Jose Claudio Casali Da Rocha,
  • Vinicius Fernando Calsavara,
  • Dirce Maria Carraro

DOI
https://doi.org/10.1002/cam4.6267
Journal volume & issue
Vol. 12, no. 15
pp. 16129 – 16141

Abstract

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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.

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