Cytokeratin positive cells in bone marrow, tumor biologic parameters of the primary tumor and survival in breast cancer patients

9517 Background: The presence of cytokeratin (CK) positive cells in bone marrow of breast cancer patients is correlated with worse clinical outcome. Therefore these cells were suggested to be derived from the primary tumor and are considered to represent an early metastatic tumor cell spread. Presence of these cells may be associated with highly aggressive breast cancer. We analyzed tumorbiologic parameters in the primary cancer, their correlation to the presence of CK positive cells in bone marrow, and survival of breast cancer patients with locally restricted disease.

METHODS: Bone marrow aspirates of 508 patients with operable breast cancer were analyzed for the presence of CK positive cells. Tissue samples of the primary tumor of 134 patients were analyzed for Ki-67, S-phase fraction, Her-2, estrogen, and progesterone receptor expression. Follow-up data were available for up to 11.2 years (median 9.5 years). Tumorbiologic factors were correlated to bone marrow status and disease-free and overall survival of the patients using chi square and log rank test.

RESULTS: 230 out of 508 patients were 'bone marrow positive' (45%). Presence of CK positive cells was negatively correlated to overall and disease-free survival (p< 0.001). Tumorbiologic parameters such as Ki-67, S-phase-fraction, steroid receptor status was also correlated to survival, however, there was no association of tumorbiologic factors and CK positive cells in bone marrow.

CONCLUSIONS: Presence of CK positive cells in bone marrow of breast cancer patients is independent from characteristics of the primary cancer. This supports the hypothesis of tumor cell dormancy characterized by persistence of these cells after adjuvant therapy and late tumor relapse. No significant financial relationships to disclose.