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

Br J Cancer. 2019 Dec;121(12):991-1000. doi: 10.1038/s41416-019-0619-y. Epub 2019 Nov 13.

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, triple-negative 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Breast Neoplasms, Male / classification
  • Breast Neoplasms, Male / epidemiology*
  • Breast Neoplasms, Male / genetics
  • Breast Neoplasms, Male / pathology
  • Disease-Free Survival
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Kinetics
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Nervous System Neoplasms / epidemiology*
  • Nervous System Neoplasms / genetics
  • Nervous System Neoplasms / pathology
  • Nervous System Neoplasms / secondary
  • Prognosis
  • Receptor, ErbB-2 / genetics
  • Triple Negative Breast Neoplasms / classification
  • Triple Negative Breast Neoplasms / epidemiology*
  • Triple Negative Breast Neoplasms / genetics
  • Triple Negative Breast Neoplasms / pathology
  • Young Adult

Substances

  • ERBB2 protein, human
  • Receptor, ErbB-2

Associated data

  • ClinicalTrials.gov/NCT03275311