Prognostic Significance of Circulating Breast Cancer Cells in Patients with Known Metastatic Disease
Abstract & Commentary
By William B. Ershler, MD, Editor
Synopsis: In a series of patients with metastatic breast cancer peripheral blood and bone marrow were assayed for the detection of breast cancer cells. Breast cancer cells were found in the bone marrow in 59% of patients but their presence did not provide prognostic information with regard to survival. In contrast, survival was significantly worse for the 41% of patients with detectable circulating breast cancer cells.
Source: Bidard F-C, et al. Ann Oncol. 2008;19:496-500.
It has been previously reported that the detection of disseminated tumor cells in the bone marrow is an independent prognostic factor for patients with early stage breast cancer.1,2 In a pooled analysis of bone marrow, breast cancer cells were detected in 31% of those with stage I through III breast cancer and such presence correlated with overall survival.1 In an earlier study from the current authors,3 15% of 621 patients with early stage breast cancer had detectable breast cancer cells within their bone marrow, and this also was shown to have an independent impact on overall survival, distant metastasis free survival and local relapse free survival. The comparative importance of bone marrow vs circulating tumor cells in breast cancer patients with metastatic disease was the purpose of the current study. For this investigation, 138 patients with known metastatic breast cancer were screened for bone marrow positive cells and a subset were also screen for peripheral blood breast cancer cells by established technique that demonstrating the presence of cytokeratin-positive cells within mononuclear cell fractions prepared either from the bone marrow or peripheral blood.3 Of the 138 patients, 110 were tested prior to the first line chemotherapy for metastatic disease. A subgroup of 37 patients with metastatic disease had peripheral blood tested for metastatic cancer cells.
The detection of breast cancer cells within the bone marrow was 59%; significantly higher than the approximate 15% found in those with early stage breast cancer.3,4 However, distinct from the findings with early stage breast cancer, for those with Stage IV disease, their presence within the bone marrow was not associated with shortened overall survival, although it was predictive of the presence of bone metastasis (P = 0.0001). In contrast, for the subgroup of 37 patients (with metastatic breast cancer) for whom peripheral blood was analyzed for breast cancer cells, their presence was associated with shorter survival (P = 0.01).
Commentary
The conclusion from this study is that for those with metastatic, rather than early stage breast cancer, circulating breast cancer cells offers greater prognostic value than detection of such cells within the bone marrow. This is valuable information, and as clinicians gain more experience with this type of added information, it is reassuring to note that bone marrow aspirations would not be required for assessment. In fact, in a recent report, using a somewhat different technique for tumor cell detection, Pachmann and colleagues found that the assessment of circulating tumor cells in patients receiving adjuvant chemotherapy for early stage breast cancer was also valuable in predicting those at high risk for relapse.2 In the current study, the high rate (59%) of bone marrow positivity was consistent with prior reports from other research centers.5 In the current report, a significant difference in overall survival was found for those who had circulating breast cancer cells. Fifteen patients were found to have circulating cells of 37 tested and unlike bone marrow detection, the presence in the peripheral blood did not predict the site of metastasis.
The overall clinical importance of this has yet to be determined. Certainly, it appears that the presence of circulating cells is a negative prognostic factor but it remains to be shown whether such an assessment is more sensitive and/or specific than those clinical parameters of which we are more familiar and comfortable. This paper and that of Pachmann,2 provide sufficient rationale for more extensive evaluation. The presence of circulating breast cancer cells that disappear after a systemic chemotherapy would seemingly be a favorable indicator of response, and those with persistent or increased numbers would similarly seem at high risk. Yet, this question needs to be addressed in a systematic way.
References
1. Braun S, et al. A pooled analysis of bone marrow micrometastasis in breast cancer. N Engl J Med. 2005;353(8):793-802.
2. Pachmann K, et al. J Clin Oncol. 2008;26(8):1208-1215.
3. Bidard FC, et al. Bone marrow micrometastases are a powerful prognostic factor in stage I to III breast cancer patients. Proceedings of the American Association for Cancer Research. 2007:5460a.
4. Wiedswang G, et al. J Clin Oncol. 2003;21(18):3469-3478.
5. Janni W, et al. Cancer. 2000;88(10):2252-2259.
In a series of patients with metastatic breast cancer peripheral blood and bone marrow were assayed for the detection of breast cancer cells. Breast cancer cells were found in the bone marrow in 59% of patients but their presence did not provide prognostic information with regard to survival. In contrast, survival was significantly worse for the 41% of patients with detectable circulating breast cancer cells.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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