Triple-negative and HER2-overexpressing breast cancers exhibit an elevated risk and an earlier occurrence of cerebral metastases

Eur J Cancer. 2009 Nov;45(16):2792-8. doi: 10.1016/j.ejca.2009.06.027. Epub 2009 Jul 28.


Purpose: Evaluation of the influence of immunohistochemically defined breast cancer (BC) subtypes and other risk factors on the development of cerebral metastases (CM).

Methods: Exploratory analysis of a hospital-based prospective tumour registry including all patients with primary BC treated in our EUSOMA breast unit between 1998 and 2006.

Results: The study cohort contained 2441 patients, including 284 patients (11.6%) with triple-negative (oestrogen receptor (ER), progesterone receptor (PR) and HER2-negative) and 245 patients (10.1%) with HER2-overexpressing BC subtypes. Overall, 80 patients (3.3%) developed CM within a median follow-up period of 47 months, 19 (23.8%) of them with triple-negative and 19 (23.8%) with HER2-positive tumours. Therefore, 6.7% of all patients with triple-negative and 7.8% of patients with HER2-positive breast cancer developed CM. Multivariate analysis indicated that the highest risk for CM was triple-negative breast cancer. Further independent risk factors were: HER2-overexpression, early onset BC (age<50 years), and large tumour size (pT3/4). Among those patients developing CM, triple-negative BC showed the shortest interval between primary diagnosis and occurrence of CM with a median of 22 months, compared to 30 and 63.5 months in HER2-positive and ER+/HER2- BC, respectively. Survival after occurrence of CM did not differ among the subtypes.

Conclusion: Patients with triple-negative or HER2-positive BC have a higher risk for CM compared with patients bearing the ER+/HER2- phenotype and develop CM earlier in the course of disease. A risk profile for CM might help adjust surveillance in high risk populations and identify patients with a need for new treatment strategies.

MeSH terms

  • Adult
  • Aged
  • Brain Neoplasms / mortality
  • Brain Neoplasms / secondary*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Disease-Free Survival
  • Female
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Phenotype
  • Receptor, ErbB-2 / metabolism*
  • Receptors, Estrogen / metabolism*
  • Receptors, Progesterone / metabolism*
  • Risk Factors


  • Receptors, Estrogen
  • Receptors, Progesterone
  • Receptor, ErbB-2