Gruber Ines, Fehm Tanja, Taran Florin Andrei, Wallwiener Markus, Hahn Markus, Wallwiener Diethelm, Krawzyck Natalia, Hoffmann Juergen, Hartkopf Andreas Daniel
Department of Obstetrics and Gynecology, University of Tuebingen, Calwerstrasse 7, 72076, Tübingen, Germany,
Breast Cancer Res Treat. 2014 Apr;144(2):353-60. doi: 10.1007/s10549-014-2853-6. Epub 2014 Feb 20.
The presence of disseminated tumor cells (DTC) in the bone marrow (BM) of early breast cancer patients at initial surgery as well as during follow-up predicts an unfavorable outcome. This study aimed to assess whether adjuvant systemic therapy has the ability to eradicate DTC and to determine the clinical impact of DTC-persistence. Between 12 and 24 months after an initial BM aspiration during primary surgery (BMA1) a second and third bone marrow aspiration (BMA2 and BMA3, respectively) was performed. DTC were identified by immunocytochemistry (pancytokeratin antibody A45-B/B3) and cytomorphology. A total of 190 patients who were DTC-positive at BMA1 were eligible for this retrospective analysis. DTC persisted in 35 of 190 (19 %) patients at BMA2 and in 11 of 71 (16 %) patients at BMA3. DTC-persistence at BMA3 was significantly lower in patients that received adjuvant endocrine therapy (p = 0.017). At BMA2, DTC-positive patients were at an increased risk of disease recurrence (HR: 4.17, 95 % CI: 1.51-11.50, p = 0.003) and death (HR: 5.02, 95 % CI: 1.156-21.83, p = 0.031). At BMA3, the presence of DTC was associated with shorter disease free survival (HR: 3.20, 95 % CI: 1.05-9.78, p = 0.010). In conclusion, a majority of initially DTC-positive primary breast cancer patients turned negative during adjuvant treatment. As DTC-persistence predicted an adverse outcome, serial DTC-determination can identify patients that will probably benefit from additional or a switch of adjuvant therapy.
早期乳腺癌患者在初次手术时以及随访期间骨髓（BM）中存在播散性肿瘤细胞（DTC）预示着不良预后。本研究旨在评估辅助全身治疗是否有能力根除DTC，并确定DTC持续存在的临床影响。在初次手术时首次骨髓穿刺（BMA1）后的12至24个月之间，进行了第二次和第三次骨髓穿刺（分别为BMA2和BMA3）。通过免疫细胞化学（全细胞角蛋白抗体A45-B/B3）和细胞形态学鉴定DTC。共有190例在BMA1时DTC阳性的患者符合这项回顾性分析的条件。190例患者中有35例（19%）在BMA2时DTC持续存在，71例患者中有11例（16%）在BMA3时DTC持续存在。接受辅助内分泌治疗的患者在BMA3时DTC持续存在的比例显著较低（p = 0.017）。在BMA2时，DTC阳性患者疾病复发风险增加（HR：4.17，95%CI：1.51 - 11.50，p = 0.003），死亡风险增加（HR：5.02，95%CI：1.156 - 21.83，p = 0.031）。在BMA3时，DTC的存在与无病生存期缩短相关（HR：3.20，95%CI：1.05 - 9.78，p = 0.010）。总之，大多数最初DTC阳性的原发性乳腺癌患者在辅助治疗期间转为阴性。由于DTC持续存在预示着不良预后，连续测定DTC可以识别可能从额外的或辅助治疗方案转换中获益的患者。
