Central Nervous System Metastasis in Patients with HER2-Positive Metastatic Breast Cancer: Patient Characteristics, Treatment, and Survival from SystHERs

Clin Cancer Res. 2019 Apr 15;25(8):2433-2441. doi: 10.1158/1078-0432.CCR-18-2366. Epub 2018 Dec 28.

Abstract

Purpose: Patients with HER2-positive metastatic breast cancer (MBC) with central nervous system (CNS) metastasis have a poor prognosis. We report treatments and outcomes in patients with HER2-positive MBC and CNS metastasis from the Systemic Therapies for HER2-positive Metastatic Breast Cancer Study (SystHERs).

Experimental design: SystHERs (NCT01615068) was a prospective, U.S.-based, observational registry of patients with newly diagnosed HER2-positive MBC. Study endpoints included treatment patterns, clinical outcomes, and patient-reported outcomes (PRO).

Results: Among 977 eligible patients enrolled (2012-2016), CNS metastasis was observed in 87 (8.9%) at initial MBC diagnosis and 212 (21.7%) after diagnosis, and was not observed in 678 (69.4%) patients. White and younger patients, and those with recurrent MBC and hormone receptor-negative disease, had higher risk of CNS metastasis. Patients with CNS metastasis at diagnosis received first-line lapatinib more commonly (23.0% vs. 2.5%), and trastuzumab less commonly (70.1% vs. 92.8%), than patients without CNS metastasis at diagnosis. Risk of death was higher with CNS metastasis observed at or after diagnosis [median overall survival (OS) 30.2 and 38.3 months from MBC diagnosis, respectively] versus no CNS metastasis [median OS not estimable: HR 2.86; 95% confidence interval (CI), 2.05-4.00 and HR 1.94; 95% CI, 1.52-2.49]. Patients with versus without CNS metastasis at diagnosis had lower quality of life at enrollment.

Conclusions: Despite advances in HER2-targeted treatments, patients with CNS metastasis continue to have a poor prognosis and impaired quality of life. Observation of CNS metastasis appears to influence HER2-targeted treatment choice.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Breast Neoplasms / etiology
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • Central Nervous System Neoplasms / diagnosis*
  • Central Nervous System Neoplasms / mortality
  • Central Nervous System Neoplasms / secondary*
  • Central Nervous System Neoplasms / therapy
  • Combined Modality Therapy
  • Disease Management
  • Female
  • Humans
  • Middle Aged
  • Odds Ratio
  • Patient Reported Outcome Measures
  • Prognosis
  • Prospective Studies
  • Receptor, ErbB-2 / metabolism*
  • Survival Analysis
  • Treatment Outcome
  • Young Adult

Substances

  • Receptor, ErbB-2

Associated data

  • ClinicalTrials.gov/NCT01615068