Department of Obstetrics and Gynaecology, University of Tuebingen, Tuebingen.
Department of Obstetrics and Gynaecology, University of Heidelberg, Heidelberg.
Ann Oncol. 2015 Jun;26(6):1155-1160. doi: 10.1093/annonc/mdv148. Epub 2015 Mar 19.
Disseminated tumor cells (DTCs) are detectable in the bone marrow (BM) of patients with primary breast cancer (PBC) and predictive of an impaired prognosis. This large trial aimed to analyze the impact of DTC detection on locoregional relapse (LR).
Patients with nonmetastatic PBC were eligible for this analysis. BM aspiration (BMA1) was carried out during primary surgery and DTCs were detected by using immunocytochemistry (A45-B/B3 antibody against pancytokeratin) and morphological criteria. At the time of LR, a subgroup of patients with nonmetastatic and operable LR received a secondary BM aspiration (BMA2).
A total of 3072 patients were included into the analysis. Of these, 732 (24%) presented with DTCs at BMA1. One hundred thirty-nine patients experienced LR and 48 of these (35%) were initially DTC positive. DTC detection was significantly associated with an increased risk of LR in univariate (P = 0.002) and multivariate analysis (P = 0.009) with a hazard ratio of 1.65 (95% confidence interval 1.13-2.40). Of the patients with LR, 55 patients were available for BMA2 and 17 of these (32%) were DTC positive. DTC detection at the time of LR was indicative of impaired overall survival (univariate analysis, P = 0.037).
DTC detection in patients with PBC is associated with an increased risk of LR, indicating that tumor cells may have the ability to recirculate from the BM to the site of the primary tumor. The impaired prognosis associated with DTC detection at the time of LR may help to identify patients that are in need for additional or more aggressive treatment.
原发性乳腺癌（PBC）患者的骨髓（BM）中可检测到播散的肿瘤细胞（DTC），并可预测预后不良。本大型试验旨在分析 DTC 检测对局部区域复发（LR）的影响。
本分析纳入了非转移性 PBC 患者。在初次手术期间进行骨髓抽吸（BMA1），并通过免疫细胞化学（针对细胞角蛋白的 A45-B/B3 抗体）和形态学标准检测 DTC。在 LR 时，将非转移性和可手术性 LR 的亚组患者进行二次骨髓抽吸（BMA2）。
共纳入 3072 例患者进行分析。其中，732 例（24%）在 BMA1 时存在 DTC。139 例患者发生 LR，其中 48 例（35%）最初为 DTC 阳性。在单因素和多因素分析中，DTC 检测与 LR 风险增加显著相关（P=0.002 和 P=0.009），风险比为 1.65（95%置信区间 1.13-2.40）。在发生 LR 的患者中，有 55 例患者可进行 BMA2，其中 17 例（32%）为 DTC 阳性。LR 时 DTC 检测提示总体生存受损（单因素分析，P=0.037）。
在 PBC 患者中检测到 DTC 与 LR 风险增加相关，表明肿瘤细胞可能具有从 BM 循环到原发性肿瘤部位的能力。LR 时 DTC 检测与预后不良相关，这可能有助于识别需要额外或更积极治疗的患者。
