Incidence of brain metastases as a first site of recurrence among women with triple receptor-negative breast cancer

Abstract

Background: This retrospective study sought to define the incidence of brain metastases as a first site of recurrence among women with triple receptor-negative breast cancer (TNBC).

Methods: A total of 2448 patients with stage I through III TNBC who were diagnosed between 1990 and 2010 were identified. We computed the cumulative incidence of developing brain metastases as a first site of recurrence at 2 and 5 years. Cox proportional hazards models were fitted to determine factors that could predict for the development of brain metastases as a first site of recurrence. The Kaplan-Meier product limit method was used to compute survival following a diagnosis of brain metastases.

Results: At a median follow-up of 39 months, 115 (4.7%) patients had developed brain metastases as a first site of recurrence. The cumulative incidence at 2 and 5 years was 3.7% (95% confidence interval [CI] = 2.9%-4.5%) and 5.4% (95% CI = 4.4%-6.5%), respectively. Among patients with stage I, II, and III disease, the 2-year cumulative incidence of brain metastases was 0.8%, 3.1%, and 8%, respectively (P < .0001). The 5-year cumulative incidence was 2.8%, 4.6%, and 9.6% among patients with stage I, II, and III disease, respectively (P < .0001). In the multivariable model, patients with stage III disease had a significant increase in the risk of developing brain metastases as a first site of recurrence (hazards ratio = 3.51; 95% CI = 1.85-6.67; P = .0001) compared to patients with stage I disease. Those with stage II disease had a nonsignificant increased risk of developing brain metastases as a first site of recurrence (hazards ratio = 1.61; 95% CI = 0.92-2.81; P = .10) compared with patients with stage I disease. Median survival following a diagnosis of brain metastases was 7.2 months (range, 5.7-9.4 months).

Conclusions: Patients with nonmetastatic TNBC have a high early incidence of developing brain metastases as a first site of recurrence, which is associated with subsequent poor survival. Patients with stage III TNBC in particular would be an ideal cohort in which to research preventive strategies.

Figure 1

Estimates of cumulative incidence of brain metastases with 95% confidence intervals for a) all patients (cumulative incidence at 2 and 5 years 3.7% and 5.4% respectively) and b) stratified by stage (cumulative incidence at 2 and 5 years for stage I 0.8% and 2.8% respectively; stage II 3.1% and 4.6% respectively; stage III 8% and 9.6% respectively)

Figure 1

Estimates of cumulative incidence of brain metastases with 95% confidence intervals for a) all patients (cumulative incidence at 2 and 5 years 3.7% and 5.4% respectively) and b) stratified by stage (cumulative incidence at 2 and 5 years for stage I 0.8% and 2.8% respectively; stage II 3.1% and 4.6% respectively; stage III 8% and 9.6% respectively)

Figure 2

Kaplan–Meier plots illustrating survival following development of metastases among patients who developed brain metastases and those who developed metastases at other sites. Median survival among those who developed brain and other metastases was 7.2 months [95% CI 5.7–9.4 months] and 11.6 months (95% CI 10.6 – 13.0 months), respectively.