骨髓中出现外周浸润肿瘤细胞（DTCs）预示着早期乳腺癌患者的生存期缩短。目前的研究探索了应用DTCs找出辅助治疗效果不佳的患者，为这些患者提供二线辅助治疗，并把DTCs作为二线辅助治疗缓解率的替代标志物。
研究方法
在这一前瞻性试验中，在2003年10月8日后完成6个疗程的FEC方案辅助化疗的1121位早期乳腺癌患者被纳入了研究。应用FEC方案辅助化疗8-12周后进行第一次骨髓穿刺，6个月后进行第二次骨髓穿刺。通过免疫细胞化学方法（应用泛细胞角蛋白mAbs）检测骨髓中是否存在DTCs。如果第二次骨髓穿刺时DTCs≥1，就进行6疗程的多西他赛治疗，在最后一次多西他赛注射后1个月和13个月进行DTC分析。主要评价项目是无病生存期。应用Log-rank统计和Cox风险比例模型（根据原发肿瘤因素和DTC状态）比较多西他赛治疗后骨髓中不含DTCs和存在DTC的患者的临床结果。
研究结果
FU信息和第二次骨髓穿刺DTC结果完整的1067位患者中，8.5%的患者第一次骨髓穿刺时DTC阳性，7.2%的患者在第二次骨髓穿刺时DTC阳性。第二次骨髓穿刺时DTC阳性的患者比阴性的患者pT和pN分期高。对72位应用多西他赛治疗后的患者二线辅助化疗后的DTCs结果进行分析发现，15位（21%）患者存在DTCs。与二线辅助化疗后DTCs阴性的患者相比，DTCs阳性的患者的无病生存期明显缩短（47%的患者复发）。而应用多西他赛治疗后DTC阴性的患者中复发率仅为8.8%，而两次骨髓穿刺时DTCs均为阴性的患者为12.7%。第二次骨髓穿刺时DTC阴性的患者的单独分析显示，与第一次骨髓穿刺DTC阴性的患者相比，只有雌激素受体阴性的、第一次骨髓穿刺DTC阳性患者生存期缩短。
结论
DTCs可以发现FEC方案化疗后复发的高危患者，应用多西他赛二线辅助化疗后DTCs的状态与生存期明显相关。结果表明，多西他赛有助于改善高危患者的预后，DTCs分析可以作为早期乳腺癌患者辅助治疗效果的替代标志物。
医脉通整理报道，转载请注明出处。
会议专题》》》2014年ASCO年会专题报道
阅读原文摘要
Clinical outcome with correlation to disseminated tumor cell (DTC) status after DTC-driven secondary adjuvant treatment with docetaxel in early breast cancer (BrCa).(Abstract Number:11011)
Authors: Bjorn Naume, Marit Synnestvedt, Ragnhild Sorum Falk, et al.
Session Type: Clinical Science Symposium, Advances in Tumor Biology
Background: Presence of DTCs in bone marrow (BM) predicts reduced survival in early BrCa. The present study explores the use of DTCs to identify adjuvant (adj) insufficiently treated patients (pts) to be offered secondary adj treatment (Tx), and as a surrogate marker for Tx response.
Methods: In this prospective trial, 1,121 early BrCa pts were enrolled after completion of 6 cycles of adj FEC chemotherapy from Oct 2003-08. BM aspiration was performed 8-12 weeks after FEC (BM1), followed by a second BM aspiration 6 months (mo) later (BM2). Presence of DTCs in BM was determined by immunocytochemistry using pan-cytokeratin mAbs. If ≥1 DTCs were present at BM2, 6 cycles (mean 5.8; range 3-6) of docetaxel (D)(100 mg/m2, 3qw) was administered, followed by DTC analysis 1 mo and 13 mo after last D infusion (post-Tx). The primary endpoint was disease free survival (DFS). Log-rank statistics and Cox proportional-hazard model were used to compare outcome in pts treated with D with no DTCs after Tx to pts with DTC persistence, and in all pts according to primary tumor factors and DTC status.
Results: Of 1,067 pts with available FU information (median 80.6 mo; end of FU Nov 2012) and a DTC result at BM2, 8.5% were DTC pos at BM1 and 7.2% at BM2. DTC pos pts at BM2 had higher pT- and pN-stage compared to BM2 neg pts (p=0.035 and p=0.098). Of 72 D-treated pts analyzed for DTCs after Tx, 15 (21%) had persistent DTCs. Pts with remaining DTCs had markedly reduced DFS (47% with relapse) compared to pts with no DTCs post-Tx (HR 6.9, 95% CI 2.2-21.7). Only 8.8% of D-treated pts with no DTCs post-Tx relapsed, compared to 12.7% of pts in the favorable group with no DTCs both at BM1 and BM2 (p=0.378, log rank). Separate analyses of pts with DTC neg status at BM2, showed that only ER neg pts with DTC pos status at BM1 had reduced survival, compared to those with no DTCs at BM1 (p=0.029).
Conclusions: DTC status detects high-risk pts after FEC chemotherapy and DTC monitoring status after secondary Tx with D correlated strongly with survival. The results indicate that D contributes to improved prognosis for high-risk pts and emphasize the potential for DTC analysis as a surrogate marker for treatment effect in adj BrCa. Clinical trial information: NCT00248703.
