早期乳腺癌中多西他赛辅助治疗后与播散性肿瘤细胞 (DTC) 状态相关的临床结果。

Clinical outcome with correlation to disseminated tumor cell (DTC) status after DTC-guided secondary adjuvant treatment with docetaxel in early breast cancer.

机构信息

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.

出版信息

J Clin Oncol. 2014 Dec 1;32(34):3848-57. doi: 10.1200/JCO.2014.56.9327. Epub 2014 Nov 3.

DOI:10.1200/JCO.2014.56.9327

PMID:25366688

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/m(2), 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.

摘要

目的

骨髓中播散肿瘤细胞（DTC）的存在可预测早期乳腺癌患者的生存情况。本研究旨在探讨使用 DTC 来识别辅助治疗不充分的患者，以便为他们提供辅助治疗，并随后评估 DTC 作为替代标志物对结果的影响。

方法

完成六周期氟尿嘧啶、表阿霉素和环磷酰胺（FEC）化疗的早期乳腺癌患者，在 FEC 后 2 至 3 个月（BM1）和 8 至 9 个月（BM2）进行骨髓抽吸。使用 pan-cytokeratin 单克隆抗体的免疫细胞化学法确定骨髓中 DTC 的存在。如果在 BM2 时存在一个或多个 DTC，则给予六周期多西紫杉醇（100mg/m2，每 3 周一次）治疗，然后在最后一次多西紫杉醇输注后 1 和 13 个月（治疗后）进行 DTC 分析。Cox 回归分析用于评估无病间隔（DFI）。

结果

在 1066 例 BM2 时 DTC 结果可及且随访信息完整的患者中（从 BM2 时间起的中位随访时间为 71.9 个月），7.2%为 DTC 阳性。在接受治疗后分析的 72 例多西紫杉醇治疗患者中，有 15 例（20.8%）仍存在 DTC。与治疗后无 DTC 的患者相比，仍存在 DTC 的患者 DFI 明显降低（46.7%的患者复发）（调整后的危险比，7.58；95%置信区间，2.3 至 24.7）。治疗后无 DTC 的多西紫杉醇治疗患者与 BM1 和 BM2 时均无 DTC 的患者 DFI 相当（12.7%的患者复发；P =.377，log-rank 检验）。