In order to determine the actual significance of DTCs in bone marrow for the outcome and survival of breast cancer patients, the literature basis is ample. To date, most experience with bone marrow screening for DTCs exists for immunocytochemical analyses. Numerous studies reported a strong prognostic impact of the presence of DTCs,8,11-18,86-88 whereas other investigations failed to do so.5,6,10,89-91 One reason for the discrepant results of clinical follow-up studies is a substantial methodologic variation (eg, sensitivity and specificity of detection antibody, lower detection rate of bone marrow biopsy as compared with bone marrow aspiration, and considerable variation in the number of cells analyzed) resulting in a wide range of detection rates between study populations.
However, even if only large, well-designed, and controlled studies are now considered for a summarizing statement on the prognostic significance of DTCs, at least 3 confounding technical factors varied considerably: (1) consistent and blinded analysis of noncarcinoma control patients, (2) diversity of antibodies used for identification of epithelial cells in bone marrow, and (3) number of cells analyzed per patient sample.
In the past, 2 studies therefore attempted to solve this dilemma, performing meta-analyses of the published studies.92,93 However, several authors suggested that the ideal way to perform a meta-analysis of survival data would be to use individual patient data.94,95 Using individual patient data instead would have the advantage of including information on patient characteristics, accounting for differences in immunoassays, and considering variability in treatment over time. Therefore, a large pooled analysis of individual patient data of 4703 breast cancer patients from 8 large studies13-18,86 now provides conclusive data on the adverse prognostic influence of presence of DTCs on the clinical outcome and survival of patients with stage I, II, and III breast cancer.29 DTCs are present in up to one-third of patients with stage I, II, and III breast cancer. As compared with women without DTCs, patients with DTCs had larger tumors, tumors with a higher histologic grade, lymph node metastases, and hormone receptor–negative tumors (for all variables, p < 0.001). The presence of DTC was a significant prognostic factor for poor overall and breast cancer–specific survival and disease-free and distant metastasis–free survival during the 10-year observation period (univariate mortality ratios, 2.15, 2.44, 2.13, and 2.33, respectively; for all, p < 0.001) (Fig. 27-2). In multivariable analysis, presence of DTCs was an independent predictor of poor patient outcome (Table 27-1).