Wiedswang Gro, Borgen Elin, Kåresen Rolf, Qvist Hanne, Janbu Jan, Kvalheim Gunnar, Nesland Jahn M, Naume Bjørn
Department of Surgery, Ullevål University Hospital, Oslo, Norway.
Clin Cancer Res. 2004 Aug 15;10(16):5342-8. doi: 10.1158/1078-0432.CCR-04-0245.
The aim of the study was to explore the value of analyzing bone marrow (BM) for the presence of isolated tumor cell(s) (ITCs) in disease-free breast cancer patients 3 years after diagnosis.
ITCs in BM at operation was found to be an independent prognostic factor in 817 breast cancer patients. Among these, 356 disease-free patients were analyzed with a second BM after 3 years follow-up (median 40 months, SD 3 months, range 29-52). ITC was detected by immunocytochemistry with anticytokeratine antibodies (AE1/AE3).
The population consisted of 70% T1 and 72% node-negative patients. ITC in BM was detected in 15%. At a median of 25 months since the second BM aspiration (66 months since diagnosis), 32 patients had developed relapse, 12 local and 20 systemic. Of the patients with ITC in BM, 21% relapsed compared with 7% of the ITC-negative patients (P < 0.001). Ten patients died of breast cancer. Survival analyses showed that ITC in BM predicted reduced distant disease-free survival (DDFS) and breast cancer specific survival (BCSS; P < 0.001, log-rank test). Uni-and multivariate analyses of the prognostic value of N, T, estrogen receptor/progesterone receptor, and BM status, histological grade, vascular invasion, p53-, c-erb-B2-, and cathepsin D expression were performed. BM status was the only independent prognostic factor for both DDFS and BCSS, whereas c-erbB-2 and N status were independent for BCSS and vascular invasion and T status for DDFS.
ITC in BM 3 years after diagnosis in disease-free breast cancer patients is an independent prognostic factor. Detection of residual disease by BM analysis at follow-up may unravel insufficient adjuvant treatment. The clinical implications should be further explored.
本研究旨在探讨分析无病乳腺癌患者诊断3年后骨髓中孤立肿瘤细胞（ITC）存在情况的价值。
在817例乳腺癌患者中，手术时骨髓中的ITC被发现是一个独立的预后因素。其中，356例无病患者在随访3年后（中位时间40个月，标准差3个月，范围29 - 52个月）进行了第二次骨髓分析。通过抗细胞角蛋白抗体（AE1/AE3）免疫细胞化学检测ITC。
研究人群包括70%的T1期患者和72%的淋巴结阴性患者。15%的患者骨髓中检测到ITC。自第二次骨髓穿刺后中位25个月（诊断后66个月），32例患者出现复发，12例为局部复发，20例为全身复发。骨髓中有ITC的患者中，21%复发，而ITC阴性患者为7%（P < 0.001）。10例患者死于乳腺癌。生存分析表明，骨髓中的ITC预示远处无病生存期（DDFS）和乳腺癌特异性生存期（BCSS）降低（P < 0.001，对数秩检验）。对N、T、雌激素受体/孕激素受体、骨髓状态、组织学分级、血管侵犯、p53、c-erb-B2和组织蛋白酶D表达的预后价值进行了单因素和多因素分析。骨髓状态是DDFS和BCSS的唯一独立预后因素，而c-erbB-2和N状态对BCSS独立，血管侵犯和T状态对DDFS独立。
无病乳腺癌患者诊断3年后骨髓中的ITC是一个独立预后因素。随访时通过骨髓分析检测残留疾病可能揭示辅助治疗不足。其临床意义应进一步探讨。
