Detection of minimal residual disease in blood and bone marrow in early stage breast cancer

Abstract

BACKGROUND:The significance of circulating tumor cells (CTCs) in blood and of disseminated tumor cells (DTCs) in bone marrow (BM) in patients with early stage breast cancer is unclear. In this study, the authors investigated the occurrence of CTCs and DTCs in women with early stage breast cancer and evaluated the correlation of their presence with other prognostic markers. METHODS: Blood and BM aspirations were collected at the time of primary breast surgery. CTCs were detected by using the CellSearch assay, and DTCs were detected by immunostaining BM aspirates for pancytokeratin. The presence of CTCs and DTCs was correlated with tumor classification (T1 vs T2), tumor histologic grade, estrogen receptor (ER) status, progesterone receptor (PR) status, human epidermal growth factor receptor 2 (HER2) status, and lymph node (LN) status. RESULTS: Of 92 patients who were included in the study, 49 had T1 tumors, and 43 had T2 tumors. CTCs were detected in 31% of patients, and DTCs were detected in 27% of patients. There was no correlation between the occurrence of CTCs and DTCs with the tumor classification (T1 vs T2) or histologic grade. CTCs were detected in 33% of patients with ER-positive disease versus 26% of patients with ER-negative disease, in 32% of patients with PR-positive disease versus 30% of patients with PR-negative disease, and in 25% of patients with HER2-positive disease versus 31% of patients with HER2-negative disease. DTCs were observed in 23% of patients with ER-positive disease versus 37% of patients with ER-negative disease, in 22% of patients with PR-positive disease versus 32% of patients with PR-negative disease, and in 0% of patients with HER2-positive disease versus 29% of patients with HER2-negative disease. CTCs and DTCs were nearly equally prevalent in both LN-positive women and LN-negative women. There was no significant correlation between the occurrence of CTCs or DTCs with tumor classification (T1 vs T2), tumor histologic grade, positive ER status, positive PR status, or positive HER2 status, and axillary LN status. CONCLUSIONS: CTCs and DTCs in women with early stage breast cancer did not correlate with the standard prognostic indicators that were considered. The implications of their occurrence in patients with early stage disease will require further large-scale studies. Cancer 2010;116:3330-7.

Minimal Residual Disease and Circulating Tumor Cells in Breast Cancer

“…Although both CTCs (10% of the patients) and DTCs (14% of the patients) were significantly associated with worse clinical outcome, DTCs were more informative than CTCs [61]. Th is and other studies [62] showed that there was no good correlation between CTC and DTC detection. However, it is not clear whether this is because CTCs and DTCs represent diff erent tumor cell populations or whether this is also related to limitations of the detection technologies used.…”

The Evolving Role of Circulating Tumor Cells in the Personalized Management of Breast Cancer: From Enumeration to Molecular Characterization

“…Between 20–30% of patients with no clinically detected metastasis have been observed to be positive for CTCs in several studies [24, 41, 42]. However, the low sensitivity of current CTC identification tests in early breast cancer is a significant impediment to their use as screening tools to diagnose breast cancer.…”

Circulating Tumour Cells: Implications and Methods of Detection

“…What role does time of sampling, amount of sample drawn or individual patient characteristics have on the quality of the assay, are a few of the questions that will need to be tackled. More studies need to be developed around CTCs present in early breast cancer, and their presence and usefulness should be correlated with clinicopathological data, and gene expression data derived from currently recommended breast cancer prognostic markers and tests, for eg: Mammaprint and Oncotype Dx (Krishnamurthy et al, 2010). CTCs have the potential of being established as a reliable prognostic or diagnostic biomarker for early breast cancer, progression to metastasis, response to treatment, and development of anti-metastatic drugs.…”