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

Women with breast cancer in a distinct stage of disease can benefit from high-dose therapy (HDT) with autologous stem cell support; however, a significant number of these patients relapse despite this intensive treatment. This study investigates the persistence of malignancy on the single-cell level. A total of 194 data sets consisting of bone marrow and blood samples obtained prior to and after HDT and of aliquots of apheresis products were searched with immunocytochemistry and reverse transcriptase polymerase chain reaction (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 of malignant cells in marrow significantly. In contrast, there was no effect on the number of circulating cancer cells. Reinfusion of contaminated apheresis products was surprisingly associated with a low number of malignant cells in bone marrow after HDT and vice versa. The impact of disseminated tumor cells in bone marrow, apheresis, and peripheral blood on disease-free survival after HDT could be investigated in a total of 165 samples. Surprisingly, neither the presence of tumor cells in marrow or blood nor in apheresis was associated with a bad prognosis in Kaplan-Meyer survival analysis. These results suggest that apheresis products and bone marrow should be regarded as different biological compartments for epithelial cancer cells. It can be concluded that complete elimination of disseminated cancer cells by HDT is not always possible. The theory of reinduction of metastatic breast cancer by accidentally reinfused contaminants is not supported by this study so far. However, further research is necessary to identify distinct cell populations with the potentially capacity to metastasize.