Influence of Bone Marrow Micrometastasis in Recurrence and Survival of Breast Cancer

Purpose: Breast cancers frequently develop distant metastasis in the early phase. The survival rate of patients depends on a distant metastasis. The occurrence of a micrometastasis has been related to the prognostic features of breast cancer, such as a lymph node metastasis and the presence of a vascular invasion. The aim of this study was to examine the presence of RNA from epithelial tumors in bone marrow from a series of breast cancer patients and its correlation with the tumor staging and disease free survival. Methods: Bone marrow samples were obtained from 59 patients with breast cancer at the time of surgery. The mononuclear fraction was separated and a nested reverse transcriptase polymerase chain reaction (RT-PCR) was carried out for the detection of keratin-19 with different two pairs of primers. After surgery, the patients were followed up for a 3-month interval. Its correlation with the tumor size, nodal involvement, stage, and recurrence was investigated. Results: A bone marrow micrometastasis was detected by nested RT-PCR for Keratin-19 mRNA in one case in 4 DCIS, 13 in 30 patients with T1, 11 in 20 patients with T2, and all 4 cases in patients with a T3 lesion. Recurrence was observed in 7 cases and all of them tested positive for a micrometastasis in the bone marrow. Conclusion: The nested RT-PCR for keratin-19 mRNA from the bone marrow in patients with breast cancer is sensitive and reliable. Moreover, early recurrence has been observed in patients with tumor mRNA present in the bone marrow. Additional studies with a large number of patients and a long term follow up are needed.