Department of Oncology, Oslo University Hospital, Radiumhospitalet, Oslo, Norway.
BMC Cancer. 2012 Dec 22;12:616. doi: 10.1186/1471-2407-12-616.
Presence of disseminated tumor cells (DTCs) in bone marrow (BM) after completion of systemic adjuvant treatment predicts reduced survival in breast cancer. The present study explores the use of DTCs to identify adjuvant insufficiently treated patients to be offered secondary adjuvant treatment intervention, and as a surrogate marker for therapy response.
A total of 1121 patients with pN1-3 or pT1c/T2G2-3pN0-status were enrolled. All had completed primary surgery and received 6 cycles of anthracycline-containing chemotherapy. BM-aspiration was performed 8-12 weeks after chemotherapy (BM1), followed by a second BM-aspiration 6 months later (BM2). DTC-status was determined by morphological evaluation of immunocytochemically detected cytokeratin-positive cells. If DTCs were present at BM2, docetaxel (100 mg/m², 3qw, 6 courses) was administered, followed by DTC-analysis 1 month (BM3) and 13 months (BM4) after the last docetaxel infusion.
Clinical follow-up (FU) is still ongoing. Here, the descriptive data from the study are presented. Of 1085 patients with a reported DTC result at both BM1 and BM2, 94 patients (8.7%) were BM1 positive and 83 (7.6%) were BM2 positive. The concordance between BM1 and BM2 was 86.5%. Both at BM1 and BM2 DTC-status was significantly associated with lobular carcinomas (p = 0.02 and p = 0.03, respectively; chi-square). In addition, DTC-status at BM2 was also associated with pN-status (p = 0.009) and pT-status (p = 0.03). At BM1 28.8% and 12.8% of the DTC-positive patients had ≥2 DTCs and ≥3 DTCs, respectively. At BM2, the corresponding frequencies were 47.0% and 25.3%. Of 72 docetaxel-treated patients analyzed at BM3 and/or BM4, only 15 (20.8%) had persistent DTCs. Of 17 patients with ≥3 DTCs before docetaxel treatment, 12 patients turned negative after treatment (70.6%). The change to DTC-negativity was associated with the presence of ductal carcinoma (p = 0.009).
After docetaxel treatment, the majority of patients experienced disappearance of DTCs. As this is not a randomized trial, the results can be due to effects of adjuvant (docetaxel/endocrine/trastuzumab) treatment and/or limitations of the methodology. The clinical significance of these results awaits mature FU data, but indicates a possibility for clinical use of DTC-status as a residual disease-monitoring tool and as a surrogate marker of treatment response.
Clin Trials Gov NCT00248703.
全身辅助治疗后骨髓（BM）中存在播散性肿瘤细胞（DTCs）可预测乳腺癌患者的生存时间缩短。本研究探索使用 DTCs 来识别辅助治疗不足的患者，为其提供二次辅助治疗干预，并作为治疗反应的替代标志物。
共纳入 1121 例 pN1-3 或 pT1c/T2G2-3pN0 期患者。所有患者均完成了原发手术，并接受了 6 周期含蒽环类药物的化疗。化疗后 8-12 周进行骨髓抽吸（BM1），随后在 6 个月后进行第二次骨髓抽吸（BM2）。DTC 状态通过免疫细胞化学检测到的细胞角蛋白阳性细胞的形态学评估来确定。如果 BM2 中有 DTC 存在，则给予多西紫杉醇（100mg/m²，3qw，6 个疗程），随后在最后一次多西紫杉醇输注后 1 个月（BM3）和 13 个月（BM4）进行 DTC 分析。
临床随访（FU）仍在进行中。这里呈现了该研究的描述性数据。在报告了 BM1 和 BM2 中均有 DTC 结果的 1085 例患者中，94 例（8.7%）患者在 BM1 时为阳性，83 例（7.6%）患者在 BM2 时为阳性。BM1 和 BM2 的一致性为 86.5%。在 BM1 和 BM2 中，DTC 状态均与小叶癌显著相关（p=0.02 和 p=0.03；卡方检验）。此外，DTC 状态在 BM2 中也与 pN 状态（p=0.009）和 pT 状态（p=0.03）相关。在 BM1 时，28.8%和 12.8%的 DTC 阳性患者分别有≥2 个和≥3 个 DTC。在 BM2 时，相应的频率分别为 47.0%和 25.3%。在分析了 BM3 和/或 BM4 中的 72 例接受多西紫杉醇治疗的患者中，只有 15 例（20.8%）患者仍存在 DTC。在 17 例接受多西紫杉醇治疗前有≥3 个 DTC 的患者中，12 例患者在治疗后转为阴性（70.6%）。DTC 转为阴性与导管癌的存在有关（p=0.009）。
多西紫杉醇治疗后，大多数患者的 DTC 消失。由于这不是一项随机试验，结果可能是由于辅助治疗（多西紫杉醇/内分泌/曲妥珠单抗）的作用和/或方法学的限制。这些结果的临床意义有待成熟的 FU 数据，但表明 DTC 状态作为残留疾病监测工具和治疗反应替代标志物的临床应用的可能性。
Clin Trials Gov NCT00248703。
