Department of Haematology and Oncology, Stavanger University Hospital, N-4068, Stavanger, Norway.
BMC Cancer. 2012 May 28;12:190. doi: 10.1186/1471-2407-12-190.
To investigate the prognostic significance of disseminated tumor cells (DTCs) in bone marrow (BM) from non-metastatic breast cancer patients before and after surgery.
Patients with non-metastatic breast cancer were consecutively recruited to this project during the years 1998-2000. Real-time RT-PCR quantification of a DTC multimarker panel consisting of cytokeratin 19, mammaglobin A and TWIST1 mRNA was performed in BM samples obtained from 154 patients three weeks (BM2) and/or six months after surgery (BM3). The results were compared to previously published data from pre-operative BM analyses for the same patients.
DTCs were identified in post-operative BM samples (BM2 and/or BM3) from 23 (15%) of the 154 patients investigated. During a median follow-up of 98 months, 10 (44%) of these patients experienced systemic relapse as compared to 16 (12%) of 131 DTC-negative patients. Kaplan-Meier estimates of systemic recurrence-free- and breast-cancer specific survival demonstrated significantly shorter survival for patients with persistent DTCs in BM after surgery (p≤0.001). By multivariate Cox regression analyses, persistent DTCs after surgery was an independent predictor of both systemic recurrence-free- (HR = 5.4, p < 0.001) and breast-cancer specific survival (HR = 5.3, p < 0.001). Furthermore, the prognostic value of DTCs in BM was similar for pre- and post surgery samples. However, patients with DTCs both before and after surgery (BM1 and BM2/3) had a particularly poor prognosis (systemic recurrence-free survival: HR = 7.2, p < 0.0001 and breast-cancer specific survival: HR = 8.0, p < 0.0001).
Detection of persistent DTCs in BM samples obtained after surgery identified non-metastatic breast cancer patients at high risk for systemic relapse, and with reduced breast-cancer specific survival. Furthermore, patients with positive DTC status both before and after surgery had a particularly poor prognosis.
研究非转移性乳腺癌患者手术前后骨髓中播散肿瘤细胞（DTC）的预后意义。
本研究于 1998-2000 年连续招募了非转移性乳腺癌患者。对 154 例患者手术前（BM1）和/或手术后 3 周（BM2）和/或 6 个月（BM3）骨髓样本中的细胞角蛋白 19、乳球蛋白 A 和 TWIST1 mRNA 的 DTC 多标记物进行实时 RT-PCR 定量。将结果与之前对同一患者进行的术前 BM 分析数据进行比较。
在 154 例患者中有 23 例（15%）的患者在术后 BM 样本（BM2 和/或 BM3）中检测到 DTC。在中位随访 98 个月期间，与 131 例 DTC 阴性患者中 16 例（12%）相比，这些患者中有 10 例（44%）发生全身复发。Kaplan-Meier 估计的无系统复发生存率和乳腺癌特异性生存率表明，术后骨髓中持续存在 DTC 的患者生存时间显著缩短（p≤0.001）。通过多变量 Cox 回归分析，术后持续存在 DTC 是无系统复发（HR=5.4，p<0.001）和乳腺癌特异性生存（HR=5.3，p<0.001）的独立预测因素。此外，BM 中 DTC 的预后价值在术前和术后样本中相似。然而，术前和术后均存在 DTC 的患者（BM1 和 BM2/3）预后尤其差（无系统复发生存率：HR=7.2，p<0.0001 和乳腺癌特异性生存率：HR=8.0，p<0.0001）。
术后骨髓样本中持续存在 DTC 可识别出发生全身复发风险高、乳腺癌特异性生存率降低的非转移性乳腺癌患者。此外，术前和术后均存在 DTC 阳性的患者预后尤其差。
