中国癌症杂志2024,Vol.34Issue(2) :185-190.DOI:10.19401/j.cnki.1007-3639.2024.02.006

BRCA1/2胚系突变对三阴性乳腺癌患者放疗后第二原发肿瘤的影响

Impact of BRCA1/2 germline mutation on the incidence of second primary cancer following postoperative radiotherapy in patients with triple-negative breast cancer

胡晓钰 蔡毓文 叶富贵 邵志敏 胡伟刚 余科达
中国癌症杂志2024,Vol.34Issue(2) :185-190.DOI:10.19401/j.cnki.1007-3639.2024.02.006

BRCA1/2胚系突变对三阴性乳腺癌患者放疗后第二原发肿瘤的影响

Impact of BRCA1/2 germline mutation on the incidence of second primary cancer following postoperative radiotherapy in patients with triple-negative breast cancer

胡晓钰 1蔡毓文 2叶富贵 2邵志敏 2胡伟刚 1余科达2
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作者信息

  • 1. 复旦大学附属肿瘤医院放疗科,复旦大学上海医学院肿瘤学系,上海 200032
  • 2. 复旦大学附属肿瘤医院乳腺外科,复旦大学上海医学院肿瘤学系,上海 200032
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摘要

背景与目的:乳腺癌易感基因1/2(BRCA1/2)的编码产物在维持机体基因组稳定性方面发挥着重要的作用.BRCA1/2致病突变是否会导致机体对放射线的脆弱度增加,从而诱发第二原发肿瘤尚不清楚.本文旨在探讨BRCA1/2基因胚系突变的三阴性乳腺癌患者术后接受放射治疗是否是增加罹患第二原发肿瘤的危险因素.方法:基于复旦大学附属肿瘤医院2007年1月1日—2014年12月31日收集的回顾性三阴性乳腺癌队列(292例为BRCA1/2突变的女性三阴性乳腺癌患者),针对其开展分析,分别在非BRCA1/2胚系突变患者(n = 261)与BRCA1/2胚系突变患者(n = 31)中进行多元logistic回归分析,以评估影响第二原发肿瘤的风险因素,并对上述两人群中的分析结果进行交互作用分析,从而评估BRCA1/2胚系突变与放疗的交互作用.本研究除特殊说明外,均采用双侧检验且检验水准α = 0.05.本研究所有样本的获得与使用均得到了复旦大学附属肿瘤医院伦理委员会的批准(050432-4-2108),且每个患者均提供了书面知情同意.结果:在BRCA1/2胚系突变患者中进行多元logistic回归分析提示术后接受放疗相对于未接受放疗显著增加了第二原发肿瘤的风险[比值比(odds ratio,OR)= 2.479,95%CI:1.971~3.118,P<0.001).而在非BRCA1/2胚系突变患者中,放疗对第二原发肿瘤的效应则不显著.BRCA1/2胚系突变与放疗对于第二原发肿瘤的发生无显著的交互作用(OR = 9.71,95%CI:0.32~295.25,P = 0.193).结论:虽然统计学分析结果显示,与未接受放疗的患者相比,BRCA1/2胚系突变的患者术后放疗会增加罹患第二原发肿瘤的风险,但BRCA1/2胚系突变与放疗对第二原发肿瘤的发生并无相互交叉作用,因而BRCA1/2胚系突变患者术后接受放疗可能并不会增加罹患第二原发肿瘤的风险.

Abstract

Background and purpose:BRCA1/2 plays an important role in maintaining the genome stability.Whether BRCA1/2 germline mutation could increase the tumor sensitivity to radiotherapy,thereby inducing secondary primary cancer after radiotherapy is unclear.This study aimed to investigate whether postoperative radiotherapy is a risk factor for the development of second primary cancer in triple-negative breast cancer(TNBC)patients with BRCA1/2 germline mutation.Methods:This research was based on a previously reported retrospective cohort,i.e.,the Fudan University Shanghai Cancer Center TNBC cohort.Between January 1,2007 and December 31,2014,a total of 292 female TNBC patients with BRCA1/2 mutation were enrolled.We performed logistic regression analysis in patients without BRCA1/2 germline mutation(n=261)and BRCA1/2 germline mutation patients(n=31),respectively,to assess the risk factors affecting the incidence of second primary cancer.We then performed interactive analysis on the above two analyses to evaluate the interactive effect between BRCA1/2 germline mutation and postoperative radiotherapy.P<0.05 indicates a statistically significant difference.The research was approved by Fudan University Shanghai Cancer Center TNBC Ethics Committee(050432-4-2108),and each patient provided written informed consent.Results:Logistic regression analysis in patients with BRCA1/2 germline mutations showed that postoperative radiotherapy significantly increased the risk of secondary primary disease compared to non-radiotherapy[odds ratio(OR)=2.475,95%confidence interval(CI):1.933-3.167,P<0.001].In patients without BRCA1/2 germline mutation,the effect of radiotherapy on the incidence of second primary tumor was not significant.There was a significant interaction between BRCA1/2 germline mutation and postoperative radiotherapy for the incidence of secondary primary cancer(OR=9.710,95%CI:0.320-295.250,P=0.193).Conclusion:Although statistical analysis results show that patients with BRCA1/2 germline mutations have an increased risk of developing a second primary tumor after postoperative radiotherapy compared to patients who have not received radiotherapy,there is no significant correlation between BRCA1/2 germline mutations and radiotherapy for the development of a second primary tumor.Therefore,patients with BRCA1/2 germline mutations who receive radiotherapy after surgery may not increase the risk of developing a second primary tumor.

关键词

乳腺癌/BRCA1/BRCA2/放疗/第二原发肿瘤

Key words

Breast cancer/BRCA1/BRCA2/Radiotherapy/Second primary cancer

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出版年

2024
中国癌症杂志
复旦大学附属肿瘤医院

中国癌症杂志

CSTPCD北大核心
影响因子:2.015
ISSN:1007-3639
参考文献量13
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