Disseminated breast cancer cells prior to and after high-dose therapy

Women with breast cancer in a distinct stage of disease can benefit from hi gh-dose therapy (HDT) with autologous stem cell support; however, a signifi cant number of these patients relapse despite this intensive treatment. Thi s study investigates the persistence of malignancy on the single-cell level . A total of 194 data sets consisting of bone marrow and blood samples obta ined prior to and after HDT and of aliquots of apheresis products were sear ched with immunocytochemistry and reverse transcriptase polymerase chain re action (RT-PCR) for disseminated cancer cells. Presence of cancer cells in the marrow is frequent prior to and after HDT, but HDT reduces the amount o f malignant cells in marrow significantly. In contrast, there was no effect on the number of circulating cancer cells. Reinfusion of contaminated aphe resis products was surprisingly associated with a low number of malignant c ells in bone marrow after HDT and vice versa. The impact of disseminated tu mor cells in bone marrow, apheresis, and peripheral blood on disease-free s urvival after HDT could be investigated in a total of 165 samples. Surprisi ngly, neither the presence of tumor cells in marrow or blood nor in apheres is was associated with a bad prognosis in Kaplan-Meyer survival analysis. T hese results suggest that apheresis products and bone marrow should be rega rded as different biological compartments for epithelial cancer cells. It c an be concluded that complete elimination of disseminated cancer cells by H DT is not always possible. The theory of reinduction of metastatic breast c ancer by accidentally reinfused contaminants is not supported by this study so far. However, further research is necessary to identify distinct cell p opulations with the potentially capacity to metastasize.