Annals of Oncology Advance Access published online on June 18, 2008
Annals of Oncology, doi:10.1093/annonc/mdn385
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
1 Department of Oncology, University Hospital, Zurich, Switzerland and International Breast Cancer Study Group (IBCSG) and Swiss Group for Clinical Cancer Research
2 Division of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia, IBCSG and Australian New Zealand Breast Cancer Trials Group
3 Department of Pathology, International Drug Development Institute, Ottignies Louvain-la-Neuve
4 Department of Oncology, Jules Bordet Institute, Brussels, Belgium, and Breast European Adjuvant Studies Team
5 Department of Biostatistical Science, IBCSG Statistical Center, Dana-Farber Cancer Institute, Boston, USA
6 Department of Pathology, European Institute of Oncology and University of Milan, Milan, Italy
7 Department of Oncology, Hospital Universitar Arnau de Vilanova, Spain and Grupo Español de Investigación de Cáncer de Mama
8 Department of Oncology, Rigshospitalet, Copenhagen, Denmark and Danish Breast Cancer Group
9 Department of Oncology, University Hospital, Linkoping, Sweden and Scandinavian Breast Cancer Group
10 1st Department of Surgery, Vienna Medical University, Vienna, Austria and Austrian Breast & Colorectal Cancer Study Group
11 Department of Haematology and Oncology, Clinica Las Condes, Santiago, Chile and Grupo Oncológico Cooperativo Chileno de Investigación
12 Department of Medical Oncology, National Institute of Oncology, Budapest, Hungary
13 Department of Oncology, St Vincent's Hospital, Dublin, Ireland and Irish Clinical Oncology Research Group
14 Department of Medicine, Breast International Group, Coordinating Office at the Institut Jules Bordet, Brussels, Belgium
* Correspondence to: PD Dr B. C. Pestalozzi, Department of Oncology, University Hospital, 8091 Zurich, Switzerland. Tel: +41-44-255-22-14; Fax: +41-44-255-45-48; E-mail: bernhard.pestalozzi{at}usz.ch
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.
adjuvant chemotherapy, breast cancer, central nervous system, meningeal carcinomatosis, taxane, trastuzumab
Deceased. Received for publication December 10, 2007. Revision received May 12, 2008. Accepted for publication May 13, 2008.