Clinical outcome of brain metastases differs significantly among breast cancer subtypes

Abstract

Brain metastases in patients with breast cancer are associated with a poor survival rate. A small number of studies have challenged this premise, suggesting that survival times following brain metastasis differ significantly between breast cancer subtypes. In the current study, overall survival (OS), brain metastases-free survival (BMFS) and survival following brain metastases (SFBM) were found to be associated with the intrinsic breast cancer subtype. A total of 1,147 patients with invasive breast cancer who were treated at the Hannover Medical School between January 2004 and December 2010 were included, from which 54 patients with brain metastases were identified. The Kaplan-Meier method or Cox regression analyses were performed for analysis of survival. OS was found to differ significantly between breast cancer subtypes: OS was significantly shorter in patients with triple-negative (TN) cancer compared with patients with human epidermal growth factor receptor (HER2)-enriched tumors (P<0.001). In addition, median BMFS times differed significantly between luminal (1,003 days), HER2-enriched (514 days) and TN breast cancer patients (460 days) (P=0.045). The median durations of SFBM were 386 days in luminal, 310 days in HER2-enriched and 147 days in TN breast cancer patients (P=0.029). The results suggested that patients with luminal breast cancer have a lower risk of brain metastases and the most favorable outcome with regard to BMFS, whereas patients with HER2-positive or TN breast cancer have a significantly higher risk of developing brain metastases. Compared with TN breast cancer, the duration of SFBM was doubled in HER2-enriched cancers. These findings may have important implications for treatment and follow-up strategies in patients with breast cancer.

Keywords: brain metastases; breast cancer; breast cancer subtypes; survival.

Figure 1.

Overall survival of breast cancer patients (n=1,147) by subtype. (A) Cumulative survival of breast cancer patients according to luminal, TN and HER2-enriched subtypes was estimated by the Kaplan-Meier method. (B) Cumulative survival of breast cancer patients according to luminal, TN, HR+/HER2+ and HR-/HER2+ subtypes was estimated by the Kaplan-Meier method. TN, triple-negative; HER2, human epidermal growth factor receptor 2; HR, hormone receptor.

Figure 2.

Brain metastases-free survival of breast cancer patients by subtype estimated by Kaplan-Meier method (n=54): Luminal [median, 1,003 days (33 months); 95% CI, 840.05–1,165.95 days], HER2-enriched [median, 514 days (17 months); 95% CI, 283.91–744.09 days], TN [median, 460 days (15 months); 95% CI, 154.33–765.67 days]. CI, confidence interval; HER2, human epidermal growth factor receptor 2; TN, triple-negative.

Figure 3.

Survival following brain metastases of breast cancer patients (n=54) by subtype, estimated by Kaplan-Meier method. (A) Survival according to luminal (median, 13 months; 95% CI, 0.00–914.26 days), HER2-enriched (median, 10 months; 95% CI, 0.00–658.19 days) and TN (median, 5 months; 95% CI, 109.64–184.36 days) subtypes. (B) Survival according to luminal (median, 13 months; 95% CI, 0.00–914.26 days), HR+/HER2+ (median, 28 months; 95% CI, 0.00–2,301.57 days), HR-/HER2+ (median, 10 months; 95% CI, 227.49–392.51 days), TN (median, 5 months; 95% CI, 109.64–184.36 days). CI, confidence interval; HER2, human epidermal growth factor receptor 2; TN, triple-negative; HR, hormone receptor.