Abstract
Breast cancer (BC) metastatic behavior varies according to the hormone receptors (HR) and HER2 statuses. Indeed, patients with triple-negative (TN) and HER2+ tumors are at higher risk of brain metastases (BM). The objective of this multinational cohort was to evaluate BM kinetics depending on the BC subtype. We retrospectively analyzed a series of BC patients with BM diagnosed in four European institutions (1996–2016). The delay between BC and BM diagnoses (BM-free survival) according to tumor biology was estimated with the Kaplan–Meier method. A multivariate analysis was performed using the Cox proportional hazards regression model. 649 women were included: 32.0% HER2−/HR+, 24.8% TN, 22.2% HER2+/HR− and 21.0% HER2+/HR+ tumors. Median age at BM diagnosis was 56 (25–85). In univariate analysis, BM-free survival differed depending on tumor biology: HER2−/HR+ 5.3 years (95% CI 4.6–5.9), HER2+/HR+ 4.4 years (95% CI 3.4–5.2), HER2+/HR− 2.6 years (95% CI 2.2–3.1) and TN 2.2 years (95% CI 1.9–2.7) (p < 0.001). It was significantly different between HR+ and HR- tumors (5.0 vs. 2.5 years, p < 0.001), and between HER2+ and HER2− tumors (3.2 vs. 3.8 years, p = 0.039). In multivariate analysis, estrogen-receptors (ER) and progesterone-receptors (PR) negativity, but not HER2 status, were independently associated with BM-free survival (hazard ratio = 1.36 for ER, p = 0.013, 1.31 for PR, p = 0.021, and 1.01 for HER2+ vs. HER2− tumors, p = 0.880). HR− and HER2+ tumors are overrepresented in BC patients with BM, supporting a higher risk of BM in these biological subtypes. HR status, but not HER2 status, impacts the kinetics of BM occurrence.
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