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桓兴医讯 DTC诱导的多西他赛二次辅助治疗早期乳腺癌的预后与治疗
文章来源:北京市朝阳区桓兴肿瘤医院 点击数: 发布时间:2014-12-10 08:20
《临床肿瘤杂志》2014年11月3日在线先发
DTC诱导的多西他赛二次辅助治疗早期乳腺癌的预后与治疗后播散肿瘤细胞(DTC)的状态相关性的临床结果
目的:
播散肿瘤细胞(DTC)存在在骨髓(BM)里,可预测早期乳腺癌的生存。本研究探讨使用DTCs识别辅助治疗不够的病人可以接受二次辅助治疗和后续的DTCs替代结果。
病人和方法:
筛选出已完成6个周期的氟尿嘧啶、表阿霉素和环磷酰胺(FEC)辅助化疗的早期乳腺癌患者,并于FEC治疗后2~3个月(BM1)和8~9个月(BM2)实施骨髓抽吸术。如果BM2中有一个或多个DTC,则需接受6个周期的多西他赛(100 mg/m2,1次/3周)治疗,并于最近一次多西他赛治疗后的第1个月和第13个月分别进行DTC分析。应用Cox回归分析评估无病间歇期(DFI)。
结果:
1 066例患者的BM2期DTC结果和可获得的随访信息(中位随访:71.9个月,来自BM2期)表明,7.2%的患者为DTC阳性。72例接受多西他赛治疗的患者于治疗后进行的DTC分析表明,15例(20.8%)存在持续性的DTC。治疗后,相比于无DTC的患者(调整后的风险比:7.58;95% CI:2.3~24.7),存在DTC的患者有显著降低的DFI(46.7%复发)。相比于那些在BM1和BM2期都没有DTC的患者(12.7%复发;P =0.377,对数秩检验),多西他赛治疗后无DTC的患者有可比的DFI(8.8%复发)。
结论:
DTC可识别FEC化疗后的高危患者,多西他赛二次治疗后的DTC状态与患者预后密切相关。这强调了DTC分析作为乳腺癌辅助治疗效果的替代标记物的可能性。
北京桓兴肿瘤医院 桓兴医讯编译组 孙晓莹
2014年11月8日 星期六
© 2014 by American Society of Clinical Oncology
Clinical Outcome With Correlation to Disseminated Tumor Cell (DTC) Status After DTC-Guided Secondary Adjuvant Treatment With Docetaxel in Early Breast Cancer
Bjørn Naume⇑, Marit Synnestvedt, Ragnhild Sørum Falk, Gro Wiedswang, Kjetil Weyde, Terje Risberg, Christian Kersten, Ingvil Mjaaland, Lise Vindi, Hilde H. Sommer, Anna Barbro Sætersdal, Maria Christine Rypdal, Cecilie Bendigtsen Schirmer, Erik Andreas Wist and Elin Borgen
+ Author Affiliations
Bjørn Naume, Marit Synnestvedt, Ragnhild Sørum Falk, Gro Wiedswang, Hilde H. Sommer, Anna Barbro Sætersdal, Maria Christine Rypdal, Cecilie Bendigtsen Schirmer, Erik Andreas Wist, and Elin Borgen, Oslo University Hospital; Bjørn Naume, Erik Andreas Wist, and Elin Borgen, K.G. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, University of Oslo, Oslo; Kjetil Weyde, Sykehuset Innlandet Trust, Gjøvik; Terje Risberg, University Hospital of Northern Norway and University of Tromsø, Tromsø; Christian Kersten, Sørlandet Hospital Trust, Kristiansand; Ingvil Mjaaland, Stavanger University Hospital, Stavanger; and Lise Vindi, Ålesund Hospital, Ålesund, Norway.
Corresponding author: Bjørn Naume, MD, PhD, Department of Oncology, Oslo University Hospital, 0242 Oslo, Norway; e-mail: bjorn.naume@medisin.uio.no.
Presented in part at the 9th International Symposium on Minimal Residual Cancer, Paris, France, September 25-27, 2013.
Abstract
Purpose The presence of disseminated tumor cells (DTCs) in bone marrow (BM) predicts survival in early breast cancer. This study explores the use of DTCs for identification of patients insufficiently treated with adjuvant therapy so they can be offered secondary adjuvant treatment and the subsequent surrogate marker potential of DTCs for outcome determination.
Patients and Methods Patients with early breast cancer who had completed six cycles of adjuvant fluorouracil, epirubicin, and cyclophosphamide (FEC) chemotherapy underwent BM aspiration 2 to 3 months (BM1) and 8 to 9 months (BM2) after FEC. Presence of DTCs in BM was determined by immunocytochemistry using pan-cytokeratin monoclonal antibodies. If one or more DTCs were present at BM2, six cycles of docetaxel (100 mg/m2, once every 3 weeks) were administered, followed by DTC analysis 1 and 13 months after the last docetaxel infusion (after treatment). Cox regression analysis was used to evaluate disease-free interval (DFI).
Results Of 1,066 patients with a DTC result at BM2 and available follow-up information (median follow-up, 71.9 months from the time of BM2), 7.2% were DTC positive. Of 72 docetaxel-treated patients analyzed for DTCs after treatment, 15 (20.8%) had persistent DTCs. Patients with remaining DTCs had markedly reduced DFI (46.7% experienced relapse) compared with patients with no DTCs after treatment (adjusted hazard ratio, 7.58; 95% CI, 2.3 to 24.7). The docetaxel-treated patients with no DTCs after treatment had comparable DFI (8.8% experienced relapse) compared with those with no DTCs both at BM1 and BM2 (12.7% experienced relapse; P = .377, log-rank test).
Conclusion DTC status identifies high-risk patients after FEC chemotherapy, and DTC monitoring status after secondary treatment with docetaxel correlated strongly with survival. This emphasizes the potential for DTC analysis as a surrogate marker for adjuvant treatment effect in breast cancer.

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