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2016年7月25日,英国《生物医学中心·癌症》发表中国军事医学科学院附属医院江泽飞团队和美国杰斐逊大学医院的研究报告,分析了肿瘤组织与循环肿瘤细胞的HER2状态差异,以及循环肿瘤细胞HER2状态对于预测组织HER2阳性转移性乳腺癌患者抗HER2疗法结局的预测价值。
该研究在新一轮抗HER2疗法开始前7天内,采用CellSearch系统检测循环肿瘤细胞HER2表达。根据既往报告提出的标准,患者被定义为循环肿瘤细胞HER2阳性或阴性。在密切随访后,通过统计学分析评估循环肿瘤细胞HER2状态与治疗结局之间的相关性。
结果,57.4%(58/101)患者检测了循环肿瘤细胞。值得注意的是,62.1%(36/58)患者组织与循环肿瘤细胞的HER2状态不一致。该不一致率可能与组织和循环肿瘤细胞HER2检测时间间隔有相关性,并且更可能存在于间隔>1年患者亚组,与间隔<1年相比(70.7%比41.2%,P=0.043)。对于无进展生存,循环肿瘤细胞阳性HER2状态被证明是有价值的预测因素,无论单变量(风险比:0.321,95%置信区间:0.156~0.62,P=0.0011)和多变量(风险比:0.383,95%置信区间:0.166~0.831,P=0.019)Cox回归分析。同时,卡普兰-迈耶生存曲线提示,循环肿瘤细胞HER2阳性患者与循环肿瘤细胞HER2阴性者相比,中位无进展生存显著延长(8.5比3.5个月,P<0.001)。
因此,循环肿瘤细胞HER2状态不同于肿瘤组织,并预测患者抗HER2疗法的不同结局。该差异可能与组织和循环肿瘤细胞HER2检测时间间隔有相关性,提示组织HER2阳性转移性乳腺癌患者实时HER2分析的必要性。
BMC Cancer. 2016 Jul 25;16(1):526.
Real-time HER2 status detected on circulating tumor cells predicts different outcomes of anti-HER2 therapy in histologically HER2-positive metastatic breast cancer patients.
Zhang S, Li L, Wang T, Bian L, Hu H, Xu C, Liu B, Liu Y, Cristofanilli M, Jiang Z.
Affiliated Hospital of Academy of Military Medical Sciences, Beijing, China.
Jefferson University Hospital, Philadelphia, PA, USA.
BACKGROUND: This study was initiated to investigate the difference in HER2 status between tumor tissue and circulating tumor cells (CTCs), as well as the predictive value of CTC HER2 status for predicting the outcomes of anti-HER2 therapy in histologically HER2-positive metastatic breast cancer (MBC) patients.
METHODS: HER2 expression on CTCs was detected using a CellSearch system within 7 days before a new line of anti-HER2 therapy was begun. According to the criterion proposed in our previous report, patients were defined as CTC HER2-positive or -negative. After close follow-up, the correlation between CTC HER2 status and the outcome of the treatment was evaluated by statistical analysis.
RESULTS: CTCs were detected in 57.4 % (58/101) of the patients. Notably, 62.1 % (36/58) of these patients had an inconsistent HER2 status between their tissue and CTCs. The discordant rate may correlate with the time interval between histological and CTC HER2 testing and is more likely to occur in the subgroup of patients with an interval of >1 year than in those with an interval <1 year (70.7 % vs. 41.2 %, P=0.043). For PFS, positive HER2 status on CTCs was shown to be a valuable predictor, both in univariate (HR=0.321, 95%CI, 0.156-0.62, P=0.0011) and multivariate (HR=0.383, 95%CI, 0.166-0.831, P=0.019) Cox regression analysis. Meanwhile, Kaplan-Meier survival curves revealed that the median PFS of CTC HER2-positive patients was significantly longer than CTC HER2-negative ones (8.5 vs. 3.5 months, P<0.001).
CONCLUSIONS: HER2 status on CTCs was different from that of tumor tissues and predicted a different outcome of the patients' anti-HER2 therapy. This difference may be correlated with the time interval between tissue and CTC HER2 testing, indicating the necessity of real-time HER2 analysis for histologically HER2-positive MBC patients.
KEYWORDS: Anti-HER2 therapy; Circulating Tumor Cells (CTCs); Human Epidermal Growth Factor Receptor 2 (HER2); Metastatic Breast Cancer (MBC); Real-time HER2 status
PMID: 27456503
DOI: 10.1186/s12885-016-2578-5
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