HER2 Receptor Conversion Is a strong Survival Predictor in Patients with Breast Cancer Brain Metastases

World Neurosurg. 2021 Aug:152:e332-e343. doi: 10.1016/j.wneu.2021.05.096. Epub 2021 May 29.

Abstract

Background: Hormone and human epidermal growth factor receptor 2 (HER2/neu) receptor status is prognostic and predictive in breast cancer (BC) and guides the choice of therapy. However, owing to receptor conversion, the receptor status can differ in metastases compared with that of the primary tumor. The aim of the present study was to analyze the prognostic value of receptor status, receptor conversion, and clinical parameters in patients with resected BC brain metastases (BMs).

Methods: Patients with BCBMs treated at our institution from July 2007 to December 2019 were eligible for the present study. The receptor status of the BC and corresponding BMs and the occurrence of receptor conversion were separately recorded for 3 common receptors: HER2/neu, estrogen receptor, and progesterone receptor. The association between the receptor status or receptor conversion and clinical parameters was adjusted for outcome-relevant patient and tumor characteristics.

Results: The final analysis included 78 patients. HER2/neu receptor status in BMs was associated with overall survival (P = 0.033). Receptor conversion was identified in 39 patients (50.0%): HER2/neu, n = 9 (11.5%); estrogen receptor, n = 22 (28.2%); and progesterone receptor, n = 25 (32.1%). In the final multivariate Cox regression analysis, HER2/neu receptor conversion (adjusted hazard ratio [aHR], 3.58; P = 0.006), Karnofsky performance status score <70% (aHR, 3.11; P = 0.048), infratentorial BM location (aHR, 2.49; P = 0.007), and age ≥55 years at BM diagnosis (aHR, 2.20; P = 0.046) were independently associated with poorer survival.

Conclusions: Of the 3 common BC receptors, only HER2/neu receptor conversion was strongly associated with the prognosis of patients with surgically treated BCBMs. The clinical relevance of the reevaluation of receptor status in BMs favors surgical treatment of patients with noneloquent BCBMs.

Keywords: Breast cancer brain metastasis; HER2; Receptor conversion; Survival.

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Biomarkers, Tumor / analysis
  • Brain Neoplasms / genetics
  • Brain Neoplasms / mortality*
  • Brain Neoplasms / secondary*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology*
  • Female
  • Humans
  • Karnofsky Performance Status
  • Middle Aged
  • Prognosis
  • Receptor, ErbB-2 / genetics*
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / genetics
  • Receptors, Progesterone / genetics
  • Survival Analysis
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • Receptors, Estrogen
  • Receptors, Progesterone
  • ERBB2 protein, human
  • Receptor, ErbB-2