Janni Wolfgang, Rack Brigitte, Schindlbeck Christian, Strobl Barbara, Rjosk Dorothea, Braun Stephan, Sommer Harald, Pantel Klaus, Gerber Bernd, Friese Klaus
I. Frauenklinik, Klinikum der Ludwig-Maximilians-Universtitaet, Muenchen, Germany.
Cancer. 2005 Mar 1;103(5):884-91. doi: 10.1002/cncr.20834.
The 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.
The 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.
Persistent 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).
Evidence 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.
近期一项大型汇总分析证实了原发性乳腺癌患者骨髓中孤立肿瘤细胞（ITCs）在初次诊断时的预后意义。如果辅助治疗后ITCs持续存在会带来相似的复发风险，那么这将成为考虑二次辅助治疗的指征。
作者分析了228例乳腺癌初诊患者（病理T1[pT1]-pT2，pN0-pN3，pM0）在无复发生存期随访期间的骨髓抽吸物，随访间隔中位数±标准差（SD）为21.3±29.1个月。使用针对细胞角蛋白（CK）的单克隆抗体A45-B/B3的标准化免疫测定法检测癌细胞。患者在初次诊断后随访的中位数±SD为49.8±32.1个月。
12.7%的患者（n = 29例）骨髓中检测到持续存在的ITCs。初次诊断后的前21个月内骨髓阳性状态更为常见（15.7%），高于随访>21个月后的比例（9.7%）。骨髓状态为阴性的患者，其无复发生存期的Kaplan-Meier估计值为149.7个月（95%置信区间[95%CI]，139.6 - 159.8个月）；在进行随访骨髓抽吸时骨髓状态为阳性的患者，该值为86.5个月（95%CI，65.7 - 107.4个月；P = 0.0003）。与骨髓状态为阳性的患者（总生存期，98.7个月；95%CI，79.7 - 117.9个月；P = 0.0008）相比，未检测到持续ITCs证据的患者总生存期显著更长（162.1个月；95%CI，152.1 - 172.0个月）。在包括骨髓状态、肿瘤大小、淋巴结状态和组织病理学分级的多因素Cox回归分析中，ITCs证据是无病生存期降低（相对风险[RR]，4.57；P <0.0001）和总生存期降低（RR，5.57；P = 0.002）的独立显著预测因素。在初次诊断后25个月至42个月之间检测到持续ITCs时，其预后相关性最大（RR，7.68）。
乳腺癌患者骨髓中持续存在ITCs的证据表明后续复发风险增加。前瞻性试验应基于骨髓状态研究二次辅助治疗的益处。
