Journal of Clinical Oncology, 2005 ASCO Annual Meeting Proceedings.
Vol 23, No 16S (June 1 Supplement), 2005: 502
© 2005 American Society of Clinical Oncology

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Abstract

Disseminated tumor cells (DTC) in bone marrow (BM) and clinical outcome: Final results of pooled analysis on 10-year survival of 4,703 breast cancer patients

Innsbruck Medcl Univ, Innsbruck, Austria; European Acad, Bozen, Italy; Institute of Tumorbiology, Hamburg, Germany

502

Background: Statistically powerful prognostic data on long-term outcome of DTC +ve breast cancer patients is needed to enable evidence-based therapeutic strategies designed to improve patient outcome. Methods: Individual patient data of 9 studies, involving 4,703 patients with stage I-III breast cancer, were combined to analyze long-term clinical outcome. A time-stratified Cox multivariable regression model was required because hazard ratios were not constant over the full length of the 10-year period. Results: The prevalence of DTC was 30.6%, and was significantly associated with larger tumor size, high grade, lymph-node metastasis (each P<0.001) and endocrine non-responsiveness (P=0.003). In the final multivariable model, DTC was an independent prognostic variable for early relapse and death. During the first 5 years of follow-up and thereafter, hazard ratios (HR) for OS were 1.81 (95%CI 1.51–2.16; P<0.001) and 1.58 (95% CI 1.12–2.22; P=0.009), respectively. Early relapse occurred significantly more often among DTC +ve patients (log rank, each P<0.001), with a multivariable HR of 1.85 (95%CI 1.58–2.14) for DFS and 2.03 (95%CI 1.72–2.39) for DDFS during the initial 5 years of follow-up. DTC was not an independent predictor for DFS and DDFS after 5 years. On univariate analysis, OS was significantly reduced for DTC +ve patients among subgroups on either endocrine therapy (n=1,499; incidence rate ratio [IRR] 2.49, 1.83–3.37; P<0.001) or chemotherapy alone (n=1,596; IRR 2.26, 1.80–2.85; P<0.001). Moreover, among 1,036 patients with pT1N0 disease, who received no systemic adjuvant treatment, those 229 DTC +ve patients had significantly worse OS (P=0.001), DFS (P=0.014) and DDFS (P=0.007), as compared to 807 DTC -ve patients. Conclusions: Presence of DTC is a strong prognostic factor of level I evidence for poor clinical outcome. Since for patients with DTC in BM it is reasonable to assume a differential susceptibility to current adjuvant therapy, as shown overall and in subgroups, consideration of DTC for clinical decision making might enable improved risk stratification in future clinical trials.

No significant financial relationships to disclose.

Abstract presentation from the 2005 ASCO Annual Meeting