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Annals of Oncology Advance Access published online on April 7, 2006
Annals of Oncology, doi:10.1093/annonc/mdl064
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© 2006 European Society for Medical Oncology
Received December 1, 2005
Revised February 10, 2006
Accepted February 28, 2006

original article

Identifying breast cancer patients at risk for Central Nervous System (CNS) metastases in trials of the International Breast Cancer Study Group (IBCSG)

B. C. Pestalozzi 1 *, D. Zahrieh 2, K. N. Price 3, S. B. Holmberg 4, J. Lindtner 5, J. Collins 6, D. Crivellari 7, M. F. Fey 8, E. Murray 9, O. Pagani 10, E. Simoncini 11, M. Castiglione-Gertsch 12, R. D. Gelber 13, A. S. Coates 14, A. Goldhirsch 15, and For the International Breast Cancer Study Group

1 Department of Oncology, University Hospital, Zürich, Switzerland and the Swiss Group for Clinical Cancer Research (SAKK)
2 IBCSG Statistical Center, Dana-Farber Cancer Institute, Boston, MA, USA
3 Frontier Science and Technology Research Foundation, Boston, MA, USA
4 Department of Surgery, SU/Moelndal's Hospital, Moelndal, Sweden
5 Department of Surgery, Institute of Oncology, Ljubljana, Slovenia
6 Department of Surgery, Royal Melbourne Hospital, Australian New Zealand Breast Cancer Trials Group, Melbourne, Australia
7 Centro di Riferimento Oncologico, Aviano, Italy
8 Department of Medical Oncology, Inselspital, Bern, Switzerland and the Swiss Group for Clinical Cancer Research (SAKK)
9 Groote Schuur Hospital and University of Cape Town, South Africa
10 Oncology Institute of Southern Switzerland, Lugano, Switzerland and the Swiss Group for Clinical Cancer Research (SAKK)
11 Oncologia Medica-Spedali Civili, Brescia, Italy
12 IBCSG Coordinating Center, and Institute of Medical Oncology, Inselspital, Bern, Switzerland
13 IBCSG Statistical Center, Dana-Farber Cancer Institute, Boston, MA, USA; Frontier Science and Technology Research Foundation, Boston, MA, USA
14 The Cancer Council Australia, Australian New Zealand Breast Cancer Trials Group and School of Public Health, University of Sydney, Australia
15 Oncology Institute of Southern Switzerland, Lugano, Switzerland and the Swiss Group for Clinical Cancer Research (SAKK); European Institute of Oncology, Milan, Italy

* To whom correspondence should be addressed.
B. C. Pestalozzi, E-mail: bernhard.pestalozzi{at}usz.ch


  Abstract

Background: We sought to determine whether a high-risk group could be defined among patients with operable breast cancer in whom a search of occult central nervous system (CNS) metastases was justified.

Patients and methods: We evaluated data from 9524 women with early breast cancer (42% node-negative) who were randomized in International Breast Cancer Study Group clinical trials between 1978 and 1999, and treated without anthracyclines, taxanes, or trastuzumab. We identified patients whose site of first event was CNS and those who had a CNS event at any time.

Results: Median follow-up was 13 years. The 10-year incidence (10-yr) of CNS relapse was 5.2% (1.3% as first recurrence). Factors predictive of CNS as first recurrence included: node-positive disease (10-yr = 2.2% for > 3 N+), estrogen receptor-negative (2.3%), tumor size > 2 cm (1.7%), tumor grade 3 (2.0%), < 35 years old (2.2%), HER2-positive (2.7%), and estrogen receptor-negative and node-positive (2.6%). The risk of subsequent CNS recurrence was elevated in patients experiencing lung metastases (10-yr = 16.4%).

Conclusion: Based on this large cohort we were able to define risk factors for CNS metastases, but could not define a group at sufficient risk to justify routine screening for occult CNS metastases.

Keywords: breast cancer; central nervous system; adjuvant chemotherapy; competing risks; CMF; metastases.
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