Prognostic significance of an increased number of micrometastatic tumor cells in the bone marrow of patients with first recurrence of breast carcinoma

Abstract

BACKGROUND Using cytokeratin (CK) as a histogenetic marker of epithelial tumor cells in the bone marrow of patients with primary breast carcinoma, a subgroup of patients with decreased survival can be identified. This study was designed to evaluate the frequency and prognostic relevance of such cells in patients with recurrent breast carcinoma. METHODS Bone marrow aspirates from 65 patients were analyzed immunocytochemically for the presence of CK positive cells. A quantitative immunoassay with monoclonal anti‐CK antibody A45‐B/B3 was used and 2 × 106 bone marrow cells per patient were evaluated. For prognostic evaluation the authors calculated a cutoff value of micrometastatic tumor cells by analogy to classification and regression tree (CART) analysis. Patients were monitored prospectively for a median of 37 months (range, 11–63 months). RESULTS Bone marrow micrometastases were present in 5 of 32 patients (16%) with locoregional recurrence and in 24 of 33 patients (73%) with distant recurrence. The bone marrow status yielded no prognostic indication for patients with locoregional recurrence. In contrast, a cutoff value of 2.5 tumor cells per 1 million bone marrow cells analyzed (2.5 × 10−6 tumor cells) correlated with a significantly different prognosis for women with distant disease. Patients with metastatic disease and a micrometastatic tumor load of > 2.5 × 10−6 tumor cells survived for a mean of 6 months (95% confidence interval [95% CI], 2.0–9.1) compared with 17 months (95% CI, 11.6–22.0) for patients with ≤ 2.5 × 10−6 tumor cells (P < 0.0001). Multivariate analysis, allowing for hormone receptor status, disease free interval prior to recurrence, manifestation site of metastases, age, and micrometastases in bone marrow, revealed that bone marrow involvement was an independent risk factor, with a hazard ratio of 7.4 (95% CI, 1.6–13.3) for disease‐related death. CONCLUSIONS An increased number of micrometastases identified in the bone marrow of patients with metastatic breast carcinoma represents an independent prognostic factor that may influence future therapeutic strategies for patients with metastatic breast carcinoma. Cancer 2000;88:2252–9. © 2000 American Cancer Society.

A European interlaboratory testing of three well‐known procedures for immunocytochemical detection of epithelial cells in bone marrow. Results from analysis of normal bone marrow

“…Furthermore, detailed genetic analysis of ICC identified single breast carcinoma cells in BM has been performed by comparative genomic hybridization (37). But at present, no standardized or easy routine method is established to further confirm the epithelial Several investigators have reported aggravated outcome when higher numbers of DTC are detected (8,15,38,39), indicating a quantitative prognostic impact of DTC. A single DTC per 2 Â 10 6 BM MNC significantly affects outcome when morphologically confirmed (15).…”

Clinical significance of proliferative potential of occult metastatic cells in bone marrow of patients with breast cancer

“…However, our series is homogeneous in terms of the type of cancer, as all patients presented breast cancer, in contrast with Solakoglu's study which included a very heterogeneous population including prostate, renal and breast cancers. The detection of isolated tumour cells in the bone marrow of patients with metastatic breast cancer has also been demonstrated to be a factor of poor prognosis (Janni et al, 2000).…”

Real-time RT–PCR detection of disseminated tumour cells in bone marrow has superior prognostic significance in comparison with circulating tumour cells in patients with breast cancer

“…cells (DEC), or transcripts of supposedly specific markers for epithelial cells, in BM aspirates (Diel et al, 1996;Braun et al, 2000;Janni et al, 2000;Gerber et al, 2001;Wiedswang et al, 2003). In these studies, the BM status is considered as a mirror for the efficacy of the metastatic process throughout the body, similar to detection of cancer cells in lymph nodes.…”