During the course of their disease, patients with triple-negative breast cancer (TNBC) and pathogenic variants (PV) in the BRCA2 gene had a higher occurrence of central nervous system (CNS) and secondary bone involvement, according to a study published in  Cancer Medicine.

Hereditary breast cancers—about 5% to 10% of all cases—are mostly due to germline PVs in BRCA1 or BRCA2 genes, the study authors noted. “Patients who develop TNBC may carry a germline PV in the BRCA1 gene, observed in up to 30% of individuals depending on the population studied. On the contrary, among [carriers of] BRCA1 [who] develop breast cancer, the TNBC subtype is found in around 80% of patients. TNBC is the neoplasia most associated with BRCA1germline PV and is more likely to develop metastases than the other breast cancer subtypes, mainly in the lungs and the CNS,” the study authors wrote, adding that carriers of BRCA2 were shown to have a higher risk for developing CNS metastases.

Since the patterns of recurrence and metastases of carriers of BRCA2 with TNBC are unknown, the study team aimed to evaluate the independent factors for CNS and bone metastasis. Data from patients with TNBC (N=388) were verified either by medical records or by BRCA1/2 genetic testing.

BRCA1/2 Pathogenic Variants Found in 21% of Participants

To assess the independent factors for CNS and bone metastases, multivariable logistic regression models were tailored to the data. To determine the correlation between the independent variables until time of death, adjustment was done using all independent variables with P<0.2 in the univariable Cox model.

The study team observed PVs in BRCA1/2 genes in 21% of total participants, with 17.7% in BRCA1 and just 3.3% in BRCA2. A total of 31% of patients developed distant metastases, and CNS and bone metastases were observed in 60% and 40% of BRCA2 PV carriers (P=0.155), respectively. The researchers noted that carriers of BRCA2 were more likely to develop bone metastases (OR, 4.06; 95% CI, 0.82-20.01; P=0.085), when compared with carriers of BRCA1 (OR, 0.6; 95% CI, 0.12-2.87; P=0.528). Carriers of BRCA1 had an OR of 0.72 (95% CI, 0.23-2.23; P=0.574), while carriers of BRCA2 had an OR of 1.75 (95% CI, 0.33-9.14; P=0.503) for CNS metastasis development (Table).

Obtaining Number of Cases Is Crucial to Help Characterize Patterns of Metastasis

“In patients with TNBC associated with germline PV in the BRCA2 gene, there was a higher number of cases with bone and CNS metastases, although it does not represent an independent risk factor for the spread of the disease to the brain or meninges and bone,” the study authors wrote. “Moreover, in this group of patients, the metastatic events occurred later.” They added that when compared with the carriers of BRCA2 and noncarriers, patients with TNBC and PV in the BRCA1gene manifested fewer metastatic events at an earlier age and showed a better survival rate.

“Since [patients with] TNBC with PV in the BRCA2 gene are a rare event, efforts to increase the number of cases from different centers are crucial to better characterize the pattern of metastasis and survival rate in this population,” the study authors wrote.