Breast cancer subtypes and survival in patients with brain metastases

TLDR

Brain metastases occur in up to one third of metastatic breast cancer patients, yet subtype‑specific incidence and prognosis data remain poorly defined. The study retrospectively analyzed 126 brain‑metastasis patients from 805 metastatic breast cancer cases, determining ER, PR, and HER2 status by immunohistochemistry (with HER2 FISH for equivocal results) and assessing trastuzumab use. Patients with brain metastases exhibited higher rates of HER2+/ER‑ and triple‑negative tumors, and triple‑receptor status emerged as a strong prognostic marker, with ER‑, HER2‑, or triple‑negative disease, older age, leptomeningeal involvement, and ≥3 extracranial sites predicting poorer survival; trastuzumab improved outcomes in HER2+ patients.

Abstract

Abstract Introduction 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. Methods Retrospective 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+. Results The 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. Conclusion MBC 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.