HER2阳性乳腺癌患者预后和三阴性乳腺癌治疗的临床及相关基础研究

发布时间：2018-04-21 15:14

本文选题：乳腺恶性肿瘤 + microRNA　；参考：《北京协和医学院》2016年博士论文

【摘要】：研究目的：约20%的HER2阳性乳腺癌患者术后曲妥珠单抗辅助治疗后出现复发或远处转移。现有的临床指标同HER2阳性乳腺癌预后相关性不强,同时也缺少能够准确预测此类患者术后复发风险的分子标记物。患者研究方法：所有入组的患者均确诊为HER2阳性乳腺癌,接受根治性手术及辅助化疗联合曲妥珠单抗治疗。我们首先利用miRNA芯片技术,比较7例术后复发和7例术后未复发患者的miRNA表达,筛选出9条差异表达的miRNA。然后我们利用RT-PCR技术,在训练集(n=101)中验证了上述9条miRNA表达同患者术后DFS的关系,并生成了基于miRNA表达的预后评价指标(miRScore) 。随后我们在内部训练集(n=57)和外部训练集(n=53)中进一步验证了miRScore的预后评估能力。结果:我们生成了基于2条miRNA (miR-4734和miR-150-5p)表达的预后评估模型,该模型能够将患者区分为复发高危组和复发低危组,两组患者间的5年DFS存在显著统计学差异。在训练集、内部训练集和外部训练集中,高危组同低危组比较,术后复发风险分别为5.35(95% CI 2.13-13.44；p0.001),3·71(95% CI 1.08-12.74,p=0.025)和3·43(95% CI 1.35-8.69；p=0.006)。将三组患者资料合并分析后(n=211),miRScore是DFS的独立预后因素,并且其对复发风险的预测能力优于其他临床病理因素。miRScore同TNM分期结合后组成的模型,具有最强的复发风险预测能力。(AUC= 0.711,95%CI0.634-0.787).结论：基于2个miRNA表达的标记物可有效预测HER2阳性乳腺癌患者曲妥珠单抗治疗后的复发风险,具有一定临床价值,有助于优化此类患者的临床处理。目的评价含长春瑞滨(NVB)联合化疗方案用于蒽环紫杉类药物治疗失败后晚期三阴性乳腺癌患者的疗效及安全性。方法回顾性分析中国医学科学院肿瘤医院内科2004年1月至2012年12月收治的晚期三阴性乳腺癌患者,入组条件包括：有可评价的转移病灶；既往在新辅助、辅助或晚期化疗阶段用过蒽环类及至少1种紫杉类药物。结果共纳入48名患者,一线化疗21人,二线化疗27人。治疗方案NVB联合铂类组(NP)22人,NVB联合卡培他滨组(NX)26人,中位随访时间70个月,整组人群有效率20.8%,临床获益率43.75%,PFS为4.35个月,OS为15.5个月。NP组较NX组有效率显著提高(33.8% vs.7.7% p=0.029),PFS显著延长(5.3m vs 3.0m,p=0.023),NP组OS有延长趋势,但无统计学差异(27.7m vs 14.8m, p=0.077)。整组人群最常见不良反应为1、2度胃肠道反应(68.8%),粒细胞下降(62.5%),NX组与NP组不良反应发生率无显著差异,NP组和NX组中分别有2人和1人出现用药延迟。结论含NVB联合方案治疗蒽环紫杉耐药的晚期三阴性乳腺癌疗效和安全性较好,NP方案的疗效可能优于NX方案,需开展随机Ⅲ期临床研究进一步验证。
[Abstract]:Objective: about 20% of patients with HER2 positive breast cancer developed recurrence or distant metastasis after adjuvant therapy. The existing clinical indicators are not strongly correlated with the prognosis of HER2 positive breast cancer and lack of molecular markers that can accurately predict the risk of recurrence in these patients. Methods: all patients were diagnosed with HER2 positive breast cancer and received radical operation and adjuvant chemotherapy combined with tratozumab. We first compared the expression of miRNA in 7 patients with postoperative recurrence and 7 patients without recurrence by using miRNA chip technique, and screened out 9 differentially expressed miRNAs. Then we used RT-PCR technique to verify the relationship between the 9 miRNA expression and postoperative DFS, and to generate a prognostic evaluation index based on miRNA expression. Then we further verified the prognostic evaluation ability of miRScore in the internal training set (n / n 57) and the external training set (n = 53). Results: a prognostic evaluation model based on the expression of two miRNA miR-4734 and miR-150-5p was developed. The model could divide the patients into high risk group and low risk group. There was a significant difference in 5-year DFS between the two groups. In the training set, internal training set and external training concentration, the risk of postoperative recurrence in high risk group was 5.35 95% CI 2.13-13.44% CI 1.08-12.74% CI 1.08-12.74% CI 1.08-12.74% CI 1.35-8.69% P 0.006, compared with low risk group. After the data of the three groups were combined and analyzed, MRS core was an independent prognostic factor of DFS, and its predictive ability of recurrence risk was superior to that of other clinicopathological factors. MiRScore combined with TNM staging model, and had the strongest predictive ability of recurrence risk. AUC = 0.711995 CI 0.634-0.787. Conclusion: two markers based on the expression of miRNA can effectively predict the risk of recurrence in patients with HER2 positive breast cancer after treatment with tritozumab. It has some clinical value and is helpful to optimize the clinical management of these patients. Objective to evaluate the efficacy and safety of combined chemotherapy regimen containing vinorelbine (NVB) in patients with advanced triple negative breast cancer after failure of anthracycline taxol therapy. Methods A retrospective analysis of patients with advanced triple negative breast cancer admitted from January 2004 to December 2012 in Cancer Hospital of the Chinese Academy of Medical Sciences was performed. Use anthracycline and at least one taxus drug during adjuvant or advanced chemotherapy. Results A total of 48 patients were included, including 21 cases of first-line chemotherapy and 27 cases of second-line chemotherapy. There were 22 patients with NVB combined with platinum group and 26 patients with NVB combined with capecitabine. The median follow-up time was 70 months. The effective rate of the whole group was 20.8, and the clinical benefit rate was 4.35 months. The OS of the NP group was 15.5 months. Compared with the NX group, the effective rate of the NP group was significantly higher than that of the NX group (33.8% vs.7.7% p0.029) PFS prolonged 5.3m vs 3.0 mp0.023NP group, but there was no statistical difference (27.7m vs 14.8 m, p0.0777m). The most common adverse reactions in the whole group were 1 ~ 2 degree gastrointestinal reaction and 68.8%. There was no significant difference in the incidence of adverse reactions between NX group and NP group. There were two cases of delayed drug use in NP group and one person in NX group. Conclusion the efficacy and safety of NVB regimen in the treatment of advanced triple negative breast cancer with anthracycline yew resistance may be better than that of NX regimen.
【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R737.9

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