Diel I J, Kaufmann M, Costa S D, Holle R, von Minckwitz G, Solomayer E F, Kaul S, Bastert G
Department of Obstetrics and Gynecology, University of Heidelberg, Federal Republic of Germany.
J Natl Cancer Inst. 1996 Nov 20;88(22):1652-8. doi: 10.1093/jnci/88.22.1652.
Approximately 30% of the patients with primary breast cancer who have no axillary lymph node involvement (i.e., lymph node negative) at the time of surgery will relapse within 10 years; 10%-20% of the patients with distant metastases will be lymph node negative at surgery. Axillary lymph node dissection, as a surgical procedure, is associated with frequent complications. A possible alternative to nodal dissection in terms of prognosis may be the immunocytochemical detection of tumor cells in bone marrow.
In a prospective study, the value of tumor cell detection (TCD) in bone marrow was compared with axillary lymph node dissection in the prognosis of primary breast cancer after surgery.
Data from 727 patients with primary, operable breast cancer were included in the analysis. All patients had surgery, including axillary lymph node dissection, from May 1985 through July 1994 at the Women's Hospital of the University of Heidelberg (Federal Republic of Germany). Bone marrow aspiration at two sites on each anterior iliac crest was performed immediately after surgery while the patients were under general anesthesia. Most patients received some type of systemic adjuvant therapy. The monoclonal antibody 2E11, directed against the polymorphic epithelial mucin TAG12, was used to detect tumor cells in bone marrow samples. The association of TCD with recognized prognostic indicators was evaluated by means of chi-squared tests. Survival without the development of distant metastases (i.e., distant disease-free survival) and overall survival were estimated by use of the Kaplan-Meier method; the logrank test was used to compare survival curves. A multivariate Cox regression analysis with stratification according to adjuvant treatment type was used to assess the independent prognostic value of TCD in bone marrow in relation to other variables. Reported P values are two-sided.
Tumor cells were detected in the bone marrow of 203 (55%) of 367 lymph node-positive patients and in 112 (31%) of 360 lymph node-negative patients. TCD was associated with larger tumors (P < .001), lymph node involvement (P = .001), and higher tumor grade (i.e., more undifferentiated) (P = .002). After a median follow-up of 36 months, patients with tumor cells in their bone marrow experienced reduced distant disease-free survival and overall survival (both P values < .001). TCD was an independent prognostic indicator for both distant disease-free survival and overall survival that was superior to axillary lymph node status, tumor stage, and tumor grade. Among patients with tumors less than 2 cm in diameter, TCD was the most powerful predictor of outcome.
TCD in the bone marrow of patients with breast cancer is a valuable prognostic tool associated with negligible morbidity. Prospective randomized studies should be performed to determine whether TCD might replace axillary lymph node dissection in a defined subgroup of patients with small tumors.
在接受手术时无腋窝淋巴结受累（即淋巴结阴性）的原发性乳腺癌患者中，约30%会在10年内复发；10% - 20%发生远处转移的患者在手术时淋巴结为阴性。腋窝淋巴结清扫术作为一种外科手术，常伴有多种并发症。就预后而言，骨髓中肿瘤细胞的免疫细胞化学检测可能是淋巴结清扫术的一种替代方法。
在一项前瞻性研究中，比较了骨髓中肿瘤细胞检测（TCD）与腋窝淋巴结清扫术对原发性乳腺癌术后预后的影响。
分析了727例原发性可手术乳腺癌患者的数据。所有患者于1985年5月至1994年7月在德国海德堡大学妇女医院接受手术，包括腋窝淋巴结清扫术。在患者全身麻醉下，术后立即在双侧髂前上棘各取两个部位进行骨髓穿刺。大多数患者接受了某种类型的全身辅助治疗。使用针对多态性上皮粘蛋白TAG12的单克隆抗体2E11检测骨髓样本中的肿瘤细胞。通过卡方检验评估TCD与公认的预后指标之间的关联。采用Kaplan - Meier方法估计无远处转移生存（即远处无病生存）和总生存情况；使用对数秩检验比较生存曲线。采用根据辅助治疗类型分层的多变量Cox回归分析，评估骨髓中TCD相对于其他变量的独立预后价值。报告的P值为双侧。
在367例淋巴结阳性患者中，203例（55%）骨髓中检测到肿瘤细胞；在360例淋巴结阴性患者中，112例（31%）检测到肿瘤细胞。TCD与肿瘤较大（P <.001）、淋巴结受累（P =.001）及肿瘤分级较高（即分化程度较低）（P =.002）相关。中位随访36个月后，骨髓中存在肿瘤细胞的患者远处无病生存和总生存均降低（P值均<.001）。TCD是远处无病生存和总生存的独立预后指标，优于腋窝淋巴结状态、肿瘤分期和肿瘤分级。在直径小于2 cm的肿瘤患者中，TCD是最强的预后预测指标。
乳腺癌患者骨髓中的TCD是一种有价值的预后工具，其发病率可忽略不计。应进行前瞻性随机研究，以确定在特定的小肿瘤患者亚组中TCD是否可替代腋窝淋巴结清扫术。
