Isolated Tumor Cells in Axillary Lymph Nodes of Breast Cancer Patients: Differential Prognostic Impact of Single Tumor Cell(s) Versus Tumor Cell Clusters, and Microanatomic Location. New Results from the Dutch MIRROR Study.
Authors: van Diest P. , Schut H. , de Boer M. , van Deurzen C. , van Dijck J. , Borm G. , Adang E. , Bult P. , Tjan-Heijnen V. 
Published: December 2010

Abstract
BackgroundThe MIRROR study is the largest breast cancer cohort study on pN0(i+) and pN1mi in the sentinel node era, with central pathology review plus restaging according to the 6th AJCC classification, and separate analyses on the impact of systemic adjuvant therapy. In patients not receiving systemic therapy, pN0(i+) as final N-status was shown to be an equally independent prognosticator for disease-free survival as pN1mi compared with pN0 (SABCS 2008, #23, oral). However, pN0(i+) is a heterogeneous group, consisting of single tumor cell(s) and clusters of cells, and consisting of locations in either sinus or parenchyma. We determined the differential impact of size and microanatomic location of nodal involvement on disease-free survival.MethodsWomen operated for breast cancer in all Dutch hospitals in the years 1998-2005, with favorable characteristics (tumor size 1-3 cm and differentiation grade I-II OR tumor size &lt;=1 cm irrespective of grade), having undergone a sentinel node procedure were selected. For this present analysis, only patients with pN0(i+) as final nodal status who had not received systemic adjuvant therapy were included (n=513). Presence of single tumor cell(s) versus tumor cell clusters, and the microanatomic location (sinus versus parenchyma) were recorded. In addition, metastatic size was measured. The primary endpoint was 5-year disease-free survival.ResultsThe 5-year disease-free survival of patients with lymph nodes containing single tumor cell(s) (n=93) was 78.6%, as compared to a 5-year disease-free survival of 77.1% of patients with small clusters of cells (n=404). After adjustment for age, log tumor size, grade, axillary treatment, and hormone receptor status, the adjusted hazard ratio for events was 1.10 (95% CI 0.67-1.78, NS) for the presence of tumor cell clusters as compared to the presence of single tumor cell(s). When including log metastasis size within the pN0(i+) group as a continuous variable in the Cox regression model, increasing metastatic size was borderline significantly associated with reduced 5-years disease-free survival with an adjusted hazard ratio of 1.27 (95% CI 1.00 – 1.61, p=0.05). The adjusted hazard ratio for events was 0.93 (95% CI 0.57-1.51, NS) for the parenchymal (n=112) versus sinusoidal microanatomic location (n=395).ConclusionSingle tumor cell(s) bear similar prognostic information as small tumor cell clusters, even though results do suggest that within the pN0(i+) group increasing size of nodal involvement is associated with reduced survival. Microanatomic location does not seem to have prognostic relevance.Support: The Netherlands organization for health research and development (ZonMw) and the Dutch Breast Cancer Trialists' Group (BOOG)
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 306.