New brain metastases after whole-brain radiotherapy of initial brain metastases in breast cancer patients: the significance of molecular subtypes (KROG 16-12)

Abstract

Purpose To identify the risk factors leading to new brain metastases (BM) following brain-directed treatment for initial BM resulting from breast cancer (BC). Methods In this multi-institutional study, 538\xa0BC patients with available follow-up imaging after brain-directed treatment for initial BM were analyzed. Tumor molecular subtypes were classified as follows: hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2−, n \u2009=\u2009136), HER2-positive (HER2+, n \u2009=\u2009253), or triple-negative BC (TNBC, n \u2009=\u2009149). Results In 37.4% of patients, new BM emerged at a median of 10.5\xa0months after brain-directed treatment for initial BM. The 1-year actuarial rate of new BM for HR+/HER2−, HER2+, and TNBC were 51.9%, 44.0%, and 69.6%, respectively ( p \u2009=\u20090.008). Initial whole-brain radiotherapy (WBRT) reduced new BM rates (22.5% reduction at 1\xa0year, p \u2009<\u20090.001) according to molecular subtype (HR+/HER2−, 42% reduction at 1\xa0year, p \u2009<\u20090.001; HER2+, 18.5%, p \u2009=\u20090.004; TNBC, 16.9%, p \u2009=\u20090.071). Multivariate analysis revealed an increased risk of new BM for the following factors: shorter intervals between primary BC diagnoses and BM ( p \u2009=\u20090.031); TNBC (relative to HR+/HER2−) ( p \u2009=\u20090.016); presence of extracranial metastases ( p \u2009=\u20090.019); number of BM (>4) ( p \u2009<\u20090.001); and BM in both tentorial regions ( p \u2009=\u20090.045). Anti-HER2 therapy in HER2+ patients ( p \u2009=\u20090.013) and initial use of WBRT ( p \u2009<\u20090.001) significantly lowered new BM development. Conclusions Tumor molecular subtypes were associated with both rates of new BM development and the effectiveness of initial WBRT. Anti-HER2 therapy in HER2+ patients significantly lowered new BM occurrence.