BACKGROUNDThe prognostic significance of isolated tumor cells (ITCs) in bone marrow (BM) from patients with breast carcinoma at the time of their primary diagnosis recently was been confirmed by a large pooled analysis. If the persistence of ITCs after adjuvant therapy confers a similar risk for recurrence, then it would be an indication to consider secondary adjuvant therapy.METHODSThe authors analyzed BM aspirates from 228 patients during recurrence‐free follow‐up at a median interval ± standard deviation (SD) of 21.3 ± 29.1 months after a primary diagnosis of breast carcinoma (pathologic T1 [pT1]–pT2, pN0–pN3, pM0). Carcinoma cells were detected using a standardized immunoassay with monoclonal antibody A45‐B/B3 directed against cytokeratin (CK). Patients were followed for a median ± SD of 49.8 ± 32.1 months after their primary diagnosis.RESULTSPersistent ITCs in BM were detected in 12.7% of patients (n = 29 patients). Positive BM status was more frequent (15.7%) within the first 21 months after primary diagnosis than after a follow‐up > 21 months (9.7%). The Kaplan–Meier estimate for mean recurrence‐free survival was 149.7 months (95% confidence interval [95% CI], 139.6–159.8 months) in patients with negative BM status and 86.5 months (95% CI, 65.7–107.4 months; P = 0.0003) in patients with positive BM status at the time patients underwent follow‐up BM aspiration. Patients who were without evidence of persistent ITCs had a significantly longer overall survival (162.1 months; 95% CI, 152.1–172.0 months) compared with patients who had positive BM status (overall survival, 98.7 months; 95% CI, 79.7–117.9 months; P = 0.0008). In multivariate Cox regression analysis that included BM status, tumor size, lymph node status, and histopathologic grade, evidence of ITCs was an independent significant predictor for reduced disease‐free survival (relative risk [RR], 4.57; P < 0.0001) and overall survival (RR, 5.57; P = 0.002). Persistent ITCs had the greatest prognostic relevance when they were detected between 25 months and 42 months after primary diagnosis (RR, 7.68).CONCLUSIONSEvidence of persistent ITCs in BM from patients with breast carcinoma indicated an increased risk for subsequent recurrence. Prospective trials should investigate the benefit of secondary adjuvant treatment on the basis of BM marrow status. Cancer 2005. © 2005 American Cancer Society.

Immunocytochemical detection of micrometastatic cells in bone marrow but not in lymph nodes is an independent prognostic risk factor in node-negative breast cancer that may have implications for surgery and stratification into adjuvant therapy trials.

While the primary surgical treatment modality seems to have no long-term impact on general QOL, certain body-image-related problems may be caused by mastectomy. Standard measuring instruments for QOL may fail to detect differences in satisfaction and adaptation with the primary surgical treatment modality.

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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.