Is risk of central nervous system (CNS) relapse related to adjuvant taxane treatment in node-positive breast cancer? Results of the CNS substudy in the intergroup Phase III BIG 02-98 Trial

Ann Oncol. 2008 Nov;19(11):1837-41. doi: 10.1093/annonc/mdn385. Epub 2008 Jun 18.

Abstract

Background: Breast cancer central nervous system (CNS) metastases are an increasingly important problem because of high CNS relapse rates in patients treated with trastuzumab and/or taxanes.

Patients and methods: We evaluated data from 2887 node-positive breast cancer patients randomised in the BIG 02-98 trial comparing anthracycline-based adjuvant chemotherapy (control arms) to anthracycline-docetaxel-based sequential or concurrent chemotherapy (experimental arms). After a median follow-up of 5 years, 403 patients had died and detailed information on CNS relapse was collected for these patients.

Results: CNS relapse occurred in 4.0% of control patients and 3.7% of docetaxel-treated patients. CNS relapse occurred in 27% of deceased patients in both treatment groups. CNS relapse was usually accompanied by neurologic symptoms (90%), and 25% of patients with CNS relapse died without evidence of extra-CNS relapse. Only 20% of patients survived 1 year from the diagnosis of CNS relapse. Prognosis of CNS relapse was worse for patients with meningeal carcinomatosis when compared with brain metastases. Unexpected findings included a higher rate of positive cerebrospinal fluid cytology (8% versus 3%) and more frequent use of magnetic resonance imaging for diagnosis (47% versus 30%) in the docetaxel-treated patients.

Conclusion: There is no evidence that adjuvant docetaxel treatment is associated with an increased frequency of CNS relapse.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / cerebrospinal fluid
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / pathology
  • Central Nervous System Neoplasms / cerebrospinal fluid
  • Central Nervous System Neoplasms / secondary*
  • Chemotherapy, Adjuvant
  • Cyclophosphamide / administration & dosage
  • Docetaxel
  • Doxorubicin / administration & dosage
  • Female
  • Fluorouracil / administration & dosage
  • Humans
  • Methotrexate / administration & dosage
  • Middle Aged
  • Neoplasm Metastasis
  • Taxoids / administration & dosage
  • Taxoids / adverse effects
  • Treatment Failure

Substances

  • Taxoids
  • Docetaxel
  • Doxorubicin
  • Cyclophosphamide
  • Fluorouracil
  • Methotrexate