gms | German Medical Science

Background: Overt metastases in breast cancer patients can occur decades following the primary diagnosis. The latent period between first manifestation of the disease and relapse is known as “tumor cell dormancy”. The purpose of this investigation was to study the presence of circulating tumor cells in relapse-free patients with long-term survival.

Methods: 35 blood samples were collected from breast cancer patients with a long-term relapse-free survival (>7 years). All samples underwent immunomagnetic purification followed by the detection of disseminated epithelial cells using two epithelial-specific antibodies (Mammaglobin / Pancytokeratin). Analysis of aberration patterns for chromosomes 1, 8 and 17 or 3 and 11 was performed by FisH (fluorescence in situ hybridization) to confirm the malignant nature of detected cells.

Results: Cytokeratin- and mammaglobin-positive cells were detected in 11 of 35 breast cancer patients. The malignancy of epithelial cells could be confirmed in six patients based on the detected aberration patterns for chromosomes 1, 8 and 17. In four patients, additional rehybridization for chromosomes 3 and 11 with centromeric DNA probes was performed and confirmed malignant nature of the detected cells. Thus, in 10 of 11 patients the malignancy of circulating epithelial cells was proven by specific aberration patterns.

Conclusions: Patients included into analysis experienced a relapse-free survival of at least 7 years and had no evidence of the disease at the time of blood sample collection. We conclude therefore that detected cells were “dormant”. Further investigation is needed with respect to (1) biological mechanisms prolonging dormancy of disseminated tumor cells and (2) mechanisms that can (re-)activate them.