Brain metastases from breast cancer: prognostic significance of HER-2 overexpression, effect of trastuzumab and cause of death

BMC Cancer. 2011 Sep 19:11:395. doi: 10.1186/1471-2407-11-395.

Abstract

Background: To access the prognostic significance of HER-2 overexpression, the effect of trastuzumab and the cause of death in patients with brain metastases (BM) from breast cancer (BC).

Methods: We analyzed the outcome of 130 patients with BM from BC who received whole-brain radiotherapy (WBRT) (without surgery or radiosurgery) between January 1998 and April 2006. Demographic data, tumor characteristics, and treatments were prospectively recorded. The impact of HER-2 overexpression and trastuzumab-based therapy on overall survival (OS) and the cause of death were evaluated.

Results: The median follow-up for the whole population was 6.25 months (mean: 9.15; range: 0.23-53). The median survival time and 1-year survival rates after BM diagnosis were 7.43 months and 35.8% (95% CI: 28-45.7) respectively. The median survival time for HER-2 negative patients (n = 78), HER-2 positive patients not treated with trastuzumab (n = 20) and HER-2 positive patients treated with trastuzumab (n = 32) were 5.9 months, 5.6 months and 19.53 months, respectively. The 1-year survival rates were 26.1%, 29.2% and 62.6% respectively, (p < 0.004). Among the 18 HER-2 positive patients treated with trastuzumab who died, 11 (61%) apparently succumbed from CNS progression, in the face of stable or responsive non-CNS disease. Trastuzumab-based therapy was associated with a 51% reduction in the risk of death (multiadjusted hazard ratio: 0.49; 95% CI, 0.29-0.83).

Conclusions: In our experience, trastuzumab-based therapy for HER-overexpressing tumors was associated with improved survival in BM BC patients. This subgroup of patients may benefit from innovative approaches, in order to obtain better intra cerebral control.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antineoplastic Agents / therapeutic use*
  • Brain Neoplasms / secondary
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Cause of Death
  • Female
  • Gene Expression
  • Humans
  • Kaplan-Meier Estimate
  • Middle Aged
  • Prognosis
  • Receptor, ErbB-2 / antagonists & inhibitors*
  • Receptor, ErbB-2 / genetics*
  • Trastuzumab
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Receptor, ErbB-2
  • Trastuzumab