Circulating tumor cells in breast cancer: correlation to bone marrow micrometastases, heterogeneous response to systemic therapy and low proliferative activity.

PURPOSE: The incidence and biological characteristics of circulating tumor cells in the blood of patients with breast cancer were examined and subgroups were evaluated in the context of systemic treatment and the presence of disseminated tumor cells in bone marrow. EXPERIMENTAL DESIGN: Circulating tumor cells were isolated from the peripheral blood of patients with breast cancer using a gradient system designed for the enrichment of circulating tumor cells (OncoQuick). Circulating tumor cells were identified with the anti-cytokeratin antibody, A45-B/B3. In subsets of patients, expression of the proliferation-associated Ki-67 antigen in circulating tumor cells and the concomitant presence of micrometastases in bone marrow were examined. RESULTS: In patients with primary breast cancer (stage M(0)), circulating tumor cells were detected in 5 of 60 patients (8.3%) after surgery and before initiation of adjuvant chemotherapy; a positive correlation to the presence of disseminated tumor cells in bone marrow was observed (P = 0.030, n = 53). During the course of adjuvant chemotherapy, repeated analysis of 20 M(0) patients revealed the occurrence of circulating tumor cells in 7 of 16 patients that were initially negative. Patients with metastatic disease (stage M(1)) showed circulating tumor cells in 25 of 63 cases (39.7%, P < 0.0001 as compared with M(0) patients), and a positive finding was correlated with elevated concentrations of the serum tumor marker CA15.3 (P = 0.0093). Performing repeated analysis in a subgroup of 25 M(1) patients, circulating tumor cells were found more frequently in patients with progressive disease than in patients with stable disease or remission (87.5% versus 43.8% of patients with circulating tumor cells, respectively; P = 0.047). Independent of the disease-stage, none of the 47 patients examined for the proliferative status of their circulating tumor cells showed coexpression of Ki-67. CONCLUSIONS: Circulating tumor cells seem to be nonproliferating cells that persist during chemotherapy. Circulating tumor cell detection is linked to disease progression and elevated tumor marker concentrations in patients with metastatic breast cancer.

Influence of preoperative mechanical bone quality and bone mineral density on aseptic loosening of total hip arthroplasty after seven years.

OBJECTIVE: To test mechanical bone quality and bone mineral density of the femoral head at the day of implantation as indicators for femoral prosthesis loosening. METHODS: Mechanical bone quality of a femoral head slice was assessed by destructive compression testing combined with bone mineral density measurements using peripheral quantitative computed tomography. Fourteen patients with walking pains were attainable for a radiographical follow-up mean 7.1 years after implantation. RESULTS: Radiolucent lines along the stem were evident in 11 of 14 femurs, most of them seen in Gruen zones 7, 6, 1, 3, 14, and showed strong correlations to preoperative bone strength (r=-0.80; P<0.001) and axial stiffness (r=-0.75; P=0.002), yet not to bone mineral density (r=-0.67; P=0.009). Slight varus deviations <3 degrees were noted in six femurs. Preoperative strength was reduced in this femurs to 54% (P=0.006), and stiffness to 61% (P=0.038), while bone mineral density did not differ significantly. CONCLUSIONS: Femoral prosthesis loosening after seven years can be predicted by mechanical bone quality of the femoral head at the time of implantation. Bone mineral density measurements may also indicate future stem loosening but have to interpreted carefully, keeping in mind a poorer predictive value. RELEVANCE: Indications and choice of type of hip arthroplasty should be balanced in osteoporotic bones in particular. While preoperative bone mineral density measurement allows the prediction of mechanical bone quality, its relevance in predicting failure in arthroplasty treatment remains unclear.