Braun S, Pantel K, Müller P, Janni W, Hepp F, Kentenich C R, Gastroph S, Wischnik A, Dimpfl T, Kindermann G, Riethmüller G, Schlimok G
I. Frauenklinik, Klinikum Innenstadt, Ludwig Maximilians University, Munich, Germany.
N Engl J Med. 2000 Feb 24;342(8):525-33. doi: 10.1056/NEJM200002243420801.
BACKGROUND: Cytokeratins are specific markers of epithelial cancer cells in bone marrow. We assessed the influence of cytokeratin-positive micrometastases in the bone marrow on the prognosis of women with breast cancer. METHODS: We obtained bone marrow aspirates from both upper iliac crests of 552 patients with stage I, II, or III breast cancer who underwent complete resection of the tumor and 191 patients with nonmalignant disease. The specimens were stained with the monoclonal antibody A45-B/B3, which binds to an antigen on cytokeratins. The median follow-up was 38 months (range, 10 to 70). The primary end point was survival. RESULTS: Cytokeratin-positive cells were detected in the bone marrow specimens of 2 of the 191 control patients with nonmalignant conditions (1 percent) and 199 of the 552 patients with breast cancer (36 percent). The presence of occult metastatic cells in bone marrow was unrelated to the presence or absence of lymph-node metastasis (P=0.13). After four years of follow-up, the presence of micrometastases in bone marrow was associated with the occurrence of clinically overt distant metastasis and death from cancer-related causes (P<0.001), but not with locoregional relapse (P=0.77). Of 199 patients with occult metastatic cells, 49 died of cancer, whereas of 353 patients without such cells, 22 died of cancer-related causes (P<0.001). Among the 301 women without lymph-node metastases, 14 of the 100 with bone marrow micrometastases died of cancer-related causes, as did 2 of the 201 without bone marrow micrometastases (P<0.001). The presence of occult metastatic cells in bone marrow, as compared with their absence, was an independent prognostic indicator of the risk of death from cancer (relative risk, 4.17; 95 percent confidence interval, 2.51 to 6.94; P<0.001), after adjustment for the use of systemic adjuvant chemotherapy. CONCLUSIONS: The presence of occult cytokeratin-positive metastatic cells in bone marrow increases the risk of relapse in patients with stage I, II, or III breast cancer.
背景：细胞角蛋白是骨髓中上皮癌细胞的特异性标志物。我们评估了骨髓中细胞角蛋白阳性微转移对乳腺癌女性患者预后的影响。 方法：我们从552例接受肿瘤完全切除的I、II或III期乳腺癌患者以及191例非恶性疾病患者的双侧髂嵴获取骨髓抽吸物。标本用与细胞角蛋白上一种抗原结合的单克隆抗体A45-B/B3染色。中位随访时间为38个月（范围10至70个月）。主要终点是生存。 结果：在191例非恶性疾病对照患者的骨髓标本中，2例（1%）检测到细胞角蛋白阳性细胞，在552例乳腺癌患者中，199例（36%）检测到。骨髓中隐匿转移细胞的存在与有无淋巴结转移无关（P = 0.13）。随访四年后，骨髓中微转移的存在与临床明显远处转移的发生及癌症相关原因导致的死亡相关（P < 0.001），但与局部区域复发无关（P = 0.77）。199例有隐匿转移细胞的患者中，49例死于癌症，而353例无此类细胞的患者中，22例死于癌症相关原因（P < 0.001）。在301例无淋巴结转移的女性中，100例有骨髓微转移的患者中有14例死于癌症相关原因，201例无骨髓微转移的患者中有2例死于癌症相关原因（P < 0.001）。在调整全身辅助化疗的使用后，与骨髓中无隐匿转移细胞相比，其存在是癌症死亡风险的独立预后指标（相对风险，4.17；95%置信区间，2.51至6.94；P < 0.001）。 结论：骨髓中隐匿的细胞角蛋白阳性转移细胞的存在增加了I、II或III期乳腺癌患者的复发风险。
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