Abstract
IntroductionBrain metastases (BM) occur in up to one third of patients with metastatic breast cancer (MBC), whose incidences and prognoses by breast cancer subtypes in BM have not been well delineated.MethodsRetrospective survival analyses were performed in 126 BM patients from 805 MBC patients treated at the National Cancer Center between August 2001 and April 2006, according to clinical characteristics, breast cancer subtypes, and receipt of trastuzumab. Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth receptor-2 (HER2) statuses were tested by immunohistochemical (IHC) staining, and HER2 FISH analysis conducted for IHC 2+.ResultsThe proportion of HER2+/ER- (29% vs 16%) and triple-negative (37% vs 25%) tumors was higher in the 126 BM patients than those without BM. While median survival after recurrence was longer in patients with luminal A disease (median survival of luminal A vs luminal B vs HER2+/ER- vs triple-negative: p = 0.0246; 39.6 vs 27.4 vs 20.9 vs 15.5 months), survival was shorter from BM to death in luminal A and triple negatives (median survival: p = 0.0113; 4.0 vs 9.2 vs 5.0 vs 3.4 months). Receipt of trastuzumab after BM was a significant variable for survival in HER2+ patients. Multivariate analyses identified ER-negative, HER2-negative, or triple-negative, as well as older age, presence of leptomeningeal disease, and three or more extracranial disease sites, as poor prognostic factors for survival after BM.ConclusionMBC patients who developed BM had higher proportions of triple-negative and HER2+/ER- tumor status. Triple receptor status is a useful prognostic marker for predicting survival after BM in metastatic breast cancer patients.
Highlights
Brain metastases (BM) occur in up to one third of patients with metastatic breast cancer (MBC), whose incidences and prognoses by breast cancer subtypes in BM have not been well delineated
While more than half of the early breast cancer (EBC) patients were luminal A, the proportion of patients with human epidermal growth factor receptor-2 (HER2)+/estrogen receptor (ER)- or triple-negative tumors was significantly higher in the BM population compared to the EBC population, suggesting that these subtypes were associated with the development of BM
The present study suggests that the patients with triple-negative tumors and HER2+/ER- tumors may have a higher risk to develop BM than the hormone receptor-positive subgroup, and no survival difference was observed between triple-negative tumors and HER2+/ERtumors after excluding patients who received trastuzumab after BM diagnosis (3.4 months vs 3.1 months, p = 0.9253)
Summary
Brain metastases (BM) occur in up to one third of patients with metastatic breast cancer (MBC), whose incidences and prognoses by breast cancer subtypes in BM have not been well delineated. Brain metastases (BM) clinically present in up to 16% of all metastatic breast cancers (MBC), autopsy series reveal approximately twice as many cases (34%) [1,2]. Of the patients with BM at autopsy, 19% are identified as having leptomeningeal disease (LMD) [1]. Recent gene expression studies using DNA microarrays have revealed the prognostic implication of breast cancer intrinsic subtypes, including the basal-like, HER2+/ER-, and two types of ER+ tumors: luminal A and luminal B subtypes [10,11].
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