2种新辅助化疗方案对可手术三阴性乳腺癌的临床疗效及其与BRCA1基因的相关性研究

Study on Clinical Efficacy of Two Neoadjuvant Chemotherapy Regiments on Operable Triple Negative Operative Breast Cancer and Its Correlation with BRCA1 Gene

关键词:  新辅助化疗  可手术三阴性乳腺癌  临床疗效  BRCA1基因  相关性研究

Key words:  neoadjuvant chemotherapy  operable triple negative breast cancer  clinical effects  BRCA1 gene  correlation study

摘要:

目的 对比分析不同新辅助化疗（neoadjuvant chemotherapy，NACT）方案在可手术三阴性乳腺癌（triple negative breast cancer，TNBC）中的临床疗效、预后及安全性，并探讨其与乳腺癌易感基因BRCA1之间的关系。方法 选取2014年1月—2016年8月惠州市中心人民医院收治的120例接受可手术TNBC患者作为研究对象，参考随机数字表法将其分为2组：TP（多西他赛+卡铂）组和TAC（多西他赛+多柔比星+环磷酰胺）组，每组60例。术前，所有患者均给予NACT，TP组给予多西他赛和卡铂；TAC组给予多西他赛、多柔比星及环磷酰胺；术后，采用基因芯片法检测所有患者肿瘤组织BRCA1突变情况，并对所有的患者进行随访3年。对比2组临床疗效、预后并分析其与BRCA1突变及不良反应的关系。结果 与TAC组比较，TP组病理学完全缓解（pathological complete response，pCR）率及总有效率（overall rate，ORR）比例明显升高（P<0.05）；2组间3年的无病生存期（disease-free survival，DFS）和无病生存率无明显差异；120例可手术TNBC患者中，BRCA1突变组为14例，BRCA1野生组106例；与BRCA1野生组比较，BRCA1突变组pCR及ORR比例均升高（P<0.05）；BRCA1突变组3年DFS和无病生存率分别为（38.34±1.48）个月和85.7%；BRCA1野生组3年DFS和无病生存率分别为（34.50±0.62）个月和82.1%，2组DFS和无病生存率无明显统计学意义；与TAC组比较，TP组3~4级血液学毒性和肝功能损伤发生率明显降低，胃肠道功能发生率有所升高（P<0.05）；但白细胞减少、肾功能损伤发生率比较中差异无统计学意义。结论 TP方案与TAC方案治疗相比，能有效提高可手术TNBC患者疗效，BRCA1突变组临床疗效更高，但不能提高无病生存率，且未增加患者的安全风险，对临床治疗具有指导意义。

Abstract:

OBJECTIVE To compare the clinical efficacy, prognosis and safety of different neoadjuvant chemotherapy (NACT) regimens in operable triple negative breast cancer(TNBC) and to explore its relationship with breast cancer susceptibility gene BRCA1. METHODS A total of 120 patients with operable TNBC admitted to Huizhou Central People's Hospital from January 2014 to August 2016 were enrolled as research subjects in the study. They were divided into two groups according to the random number table: TP(docetaxel+carboplatin) group and TAC(docetaxel+doxorubicin+cyclophosphamide) group, 60 cases in each group. Before surgery, all patients were given NACT, TP group was given docetaxel and carboplatin; TAC group was given docetaxel, doxorubicin and cyclophosphamide; after surgery, gene chip method was used to detect mutation of tumor tissue BRCA1 in all patients. All patients were followed for 3 years. The clinical efficacy and prognosis of the two groups were compared and analyzed for their relationship with BRCA1 mutation and toxic side effects. RESULTS Compared with the TAC group, the proportion of pathological complete response(pCR) rate and overall rate(ORR) in the TP group was significantly higher(P<0.05). There was no significant difference in disease-free survival(DFS) and disease-free survival between the two groups for 3 years. In 120 cases of operable TNBC patients, there were 14 cases in BRCA1 mutation group and 106 cases in BRCA1 wild group. Compared with BRCA1 wild group, the proportion of pCR and ORR in BRCA1 mutation group increased(P<0.05). The 3-year DFS and disease-free survival rates of the BRCA1 mutation group were (38.34±1.48)months and 85.7%, respectively. The 3-year DFS and disease-free survival rates of the BRCA1 wild group were (34.50±0.62)months and 82.1%, respectively. There was no significant difference in DFS and disease-free survival rates between the two groups. Compared with the TAC group, the incidence of hematological toxicity and liver function damage in grades 3-4 of TP group was significantly decreased, and the incidence of gastrointestinal function was increased(P<0.05). There was no significant difference in the incidence of leukopenia and renal dysfunction. CONCLUSION Compared with TAC regimen, TP regimen can effectively improve the clinical efficacy of operable TNBC patient. The BRCA1 mutation group has higher clinical efficacy, but it can not improve disease-free survival rate, and does not increase the safety risk of patients. It has guiding significance for clinical treatment.