Impact of breast cancer molecular subtypes on the incidence, kinetics and prognosis of central nervous system metastases in a large multicentre real-life cohort

Abstract

BACKGROUND: Metastatic breast cancer (MBC) behaviour differs depending on hormone receptors (HR) and human epidermal growth factor receptor (HER2) statuses. METHODS: The kinetics of central nervous system (CNS) metastases (CNS metastasis-free survival, CNSM-FS) and subsequent patient's prognosis (overall survival, OS) according to the molecular subtype were retrospectively assessed in 16703 MBC patients of the ESME nationwide multicentre MBC database (Kaplan-Meier method). RESULTS: CNS metastases occurred in 4118 patients (24.6%) (7.2% at MBC diagnosis and 17.5% later during follow-up). Tumours were HER2−/HR+ (45.3%), HER2+/HR+ (14.5%), HER2+/HR− (14.9%) and triple negative (25.4%). Median age at CNS metastasis diagnosis was 58.1 years (range: 22.8-92.0). The median CNSM-FS was 10.8 months (95% CI: 16.5-17.9) among patients who developed CNS metastases. Molecular subtype was independently associated with CNSM-FS (HR = 3.45, 95% CI: 3.18-3.75, triplenegative and HER2−/HR+ tumours). After a 30-month follow-up, median OS after CNS metastasis diagnosis was 7.9 months (95% CI: 7.2-8.4). OS was independently associated with subtypes: median OS was 18.9 months (HR = 0.57, 95% CI: 0.50-0.64) for HER2+/ HR+ , 13.1 months (HR = 0.72, 95% CI: 0.65-0.81) for HER2+/HR−, 4.4 months (HR = 1.55, 95% CI: 1.42-1.69) for triple-negative and 7.1 months for HER2−/HR+ patients (p <0.0001). CONCLUSIONS: Tumour molecular subtypes strongly impact incidence, kinetics and prognosis of CNS metastases in MBC patients. CLINICAL TRIAL REGISTRATION: NCT03275311.

Treatment strategies for breast cancer brain metastases

“…OS was independently associated with subtypes: the median OS after BM diagnosis was 18.9 months for ER + /HER2 + , 13.1 months for ER -/HER2 + , 7.1 months for ER + / HER2and 4.4 months for ER -/HER2 -(P < 0.0001). 2 These differences in OS following BM diagnosis are mostly due to available and efficient systemic treatment-before the anti-HER2 therapy revolution, survival outcomes were comparable between patients with HER2 + and HER2 -MBC. In a retrospective study, Dawood et al…”

“…1 In a 2019 retrospective assessment of the metastatic breast cancer (MBC) cohort from the ongoing Epidemiological Strategy and Medical Economics (ESME) research programme, the risk of developing BM is estimated to be as high as 25% among patients with advanced breast cancer (BC), with a median time of BM occurrence 2-3 years after the initial BC diagnosis. 2 What is the history of BCBM? The main hypothesis is that cancer cells from breast parenchyma must undergo epithelialto-mesenchymal transition (EMT) to enter the bloodstream, survive haematological diffusion and implant into the CNS after extravasation and a further step of reverse mesenchymal-toepithelial transition (MET).…”

Predicting Prognosis of Breast Cancer Patients with Brain Metastases in the BMBC Registry—Comparison of Three Different GPA Prognostic Scores

“…In comparison, 14% of patients in our cohort did not receive radiotherapy or local treatment of the brain which might explain the shorter survival times in our cohort in comparison to original cohorts [ 8 ]. However, the median OS time of 8.7 months is in the range of published real-world data of BC patients with BM [ 14 ].…”

Evolving treatment strategies of brain metastases from breast cancer: current status and future direction

“…15,16 The reported median overall survival (OS) for patients with luminal and HER2-positive disease was 7.1-18.9 and 13.1-16.5 months, respectively, while for patients with TNBC, OS was 4.4-4.9 months. 6,17 Therefore, management of patients with BM from BC is a significant issue directly related to quality of life and survival. Moreover, the tumor subtypes should be considered when treating BM as well as when designing new clinical trials.…”