Impact of <italic style="font-style: italic">BRCA</italic>1/2 germline mutation on the incidence of second primary cancer following postoperative radiotherapy in patients with triple-negative breast cancer

Xiaoyu HU; Yuwen CAI; Fugui YE; Zhimin SHAO; Weigang HU; Keda YU

doi:10.19401/j.cnki.1007-3639.2024.02.006

您当前的位置：

首页 >

文章列表页 >

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

Article | 更新时间：2025-12-31

- Impact of BRCA1/2 germline mutation on the incidence of second primary cancer following postoperative radiotherapy in patients with triple-negative breast cancer
- China Oncology Vol. 34, Issue 2, Pages: 185-190(2024)
- 作者机构：
  
  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
- 作者简介：
- 基金信息：
- DOI：10.19401/j.cnki.1007-3639.2024.02.006
  CLC： R737.9
- Received：24 October 2023，
  
  Revised：2024-02-18，
  
  Published：29 February 2024
- 稿件说明：
移动端阅览
Xiaoyu HU, Yuwen CAI, Fugui YE, et al. Impact of BRCA1/2 germline mutation on the incidence of second primary cancer following postoperative radiotherapy in patients with triple-negative breast cancer[J]. China Oncology, 2024, 34(2): 185-190.
DOI：

Xiaoyu HU, Yuwen CAI, Fugui YE, et al. Impact of BRCA1/2 germline mutation on the incidence of second primary cancer following postoperative radiotherapy in patients with triple-negative breast cancer[J]. China Oncology, 2024, 34(2): 185-190. DOI： 10.19401/j.cnki.1007-3639.2024.02.006.

摘要

背景与目的：

乳腺癌易感基因1/2（

BRCA

1/2）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。

BRCA

1/2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

BRCA

1/2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

BRCA

1/2突变的女性三阴性乳腺癌患者），针对其开展分析，分别在非

BRCA

1/2胚系突变患者（

= 261）与

BRCA

1/2胚系突变患者（

= 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

BRCA

1/2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

= 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

BRCA

1/2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，

0.001）。而在非

BRCA

1/2胚系突变患者中，放疗对第二原发肿瘤的效应则不显著。

BRCA

1/2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，

= 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，

BRCA

1/2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

BRCA

1/2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

BRCA

1/2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:

BRCA

1/2 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 w

hether postoperative radiotherapy is a risk factor for the development of second primary cancer in triple-negative breast cancer (TNBC) patients with

BRCA

1/2 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

BRCA

1/2 mutation were enrolled. We performed logistic regression analysis in patients without

BRCA

1/2 germline mutation (

=261) and

BRCA

1/2 germline mutation patients (

=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

BRCA

1/2 germline mutation and postoperative radiotherapy.

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

BRCA

1/2 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

0.001

]

. In patients without

BRCA

1/2 germline mutation

the effect of radiotherapy on the incidence of second primary tumor was not significant. There was a significant interaction between

BRCA

1/2 germline mutation and postoperative radiotherapy for the incidence of secondary primary cancer (OR=9.710

95%

: 0.320-295.250

=0.193).

Conclusion:

Although statistical analysis results show that patients with

BRCA

1/2 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

BRCA

1/2 germline mutations and radiotherapy for the development of a second primary tumor. Therefore

patients with

BRCA

1/2 germline mutations who receive radiotherapy after surgery may not increase the risk of developing a second primary tumor.

关键词

Keywords

references

SUNG H , FERLAY J , SIEGEL R L , et al . Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J ] . CA Cancer J Clin , 2021 , 71 ( 3 ): 209 - 249 . DOI: 10.3322/caac.v71.3 http://doi.org/10.3322/caac.v71.3 https://acsjournals.onlinelibrary.wiley.com/toc/15424863/71/3 https://acsjournals.onlinelibrary.wiley.com/toc/15424863/71/3

GIAQUINTO ANGELA N , HYUNA S , MILLER KIMBERLY D , et al . Breast cancer statistics, 2022 [J ] . CA a Cancer J Clin , 2022 , 72 ( 6 ): 524 - 541 . DOI: 10.3322/caac.v72.6 http://doi.org/10.3322/caac.v72.6 https://acsjournals.onlinelibrary.wiley.com/toc/15424863/72/6 https://acsjournals.onlinelibrary.wiley.com/toc/15424863/72/6

JIANG Y Z , MA D , SUO C , et al . Genomic and transcriptomic landscape of triple-negative breast cancers: subtypes and treatment strategies [J ] . Cancer Cell , 2019 , 35 ( 3 ): 428 - 440 .e5. DOI: 10.1016/j.ccell.2019.02.001 http://doi.org/10.1016/j.ccell.2019.02.001 https://linkinghub.elsevier.com/retrieve/pii/S1535610819300960 https://linkinghub.elsevier.com/retrieve/pii/S1535610819300960

中国医师协会精准治疗委员会乳腺癌专业委员会, 中华医学会肿瘤学分会乳腺肿瘤学组, 中国抗癌协会乳腺癌专业委员会 . 中国乳腺癌患者 BRCA 1/2基因检测与临床应用专家共识(2018年版) [J ] . 中国癌症杂志 , 2018 , 28 ( 10 ): 787 - 798 . DOI: 10.19401/j.cnki.1007-3639.2018.10.011 http://doi.org/10.19401/j.cnki.1007-3639.2018.10.011

Breast cancer Professional Committee of Precision Therapy Committee of Chinese Medical Doctor Association, Breast Cancer Group of Cancer Branch of Chinese Medical Association, breast cancer Professional Committee of China Anti-Cancer Association . Expert cons ensus on BRCA 1/2 gene detection and clinical application of breast cancer patients in China (2018 edition) [J ] . China Oncol , 2018 , 28 ( 10 ): 787 - 798 .

KUCHENBAECKER K B , HOPPER J L , BARNES D R , et al . Risks of breast, ovarian, and contralateral breast cancer for BRCA 1 and BRCA 2 mutation carriers [J ] . JAMA , 2017 , 317 ( 23 ): 2402 - 2416 . DOI: 10.1001/jama.2017.7112 http://doi.org/10.1001/jama.2017.7112 http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2017.7112 http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2017.7112

中国抗癌协会乳腺癌专业委员会, 中华医学会肿瘤学分会乳腺肿瘤学组 . 中国抗癌协会乳腺癌诊治指南与规范(2024年版) [J ] . 中国癌症杂志 , 2023 , 33 ( 12 ): 1092 - 1187 . DOI: 10.19401/j.cnki.1007-3639.2023.12.004 http://doi.org/10.19401/j.cnki.1007-3639.2023.12.004

The Society of Breast Cancer China Anti-Cancer Association, Breast Oncology Group of the Oncology Branch of the Chinese Medical Association . Guidelines for breast cancer diagnosis and treatment by China Anti-Cancer Association (2024 edition) [J ] . China Oncol , 2023 , 33 ( 12 ): 1092 - 1187 .

LEE W H , BOYER T G . BRCA 1 and BRCA 2 in breast cancer [J ] . Lancet , 2001 , 358 ( Suppl ): S5 . DO I: 10.1016/S0140-6736(01)07018-0 http://doi.org/10.1016/S0140-6736(01)07018-0 https://linkinghub.elsevier.com/retrieve/pii/S0140673601070180 https://linkinghub.elsevier.com/retrieve/pii/S0140673601070180

DROOGER J C , HOONING M J , SEYNAEVE C M , et al . Diagnostic and therapeutic ionizing radiation and the risk of a first and second primary breast cancer, with special attention for BRCA 1 and BRCA 2 mutation carriers: a critical review of the literature [J ] . Cancer Treat Rev , 2015 , 41 ( 2 ): 187 - 196 . DOI: 10.1016/j.ctrv.2014.12.002 http://doi.org/10.1016/j.ctrv.2014.12.002 https://linkinghub.elsevier.com/retrieve/pii/S0305737214001947 https://linkinghub.elsevier.com/retrieve/pii/S0305737214001947

丁高峰 , 郭雷鸣 , 陆寓非 . 乳腺癌患者HER2和BRCA1表达与放疗敏感性的关系研究 [J ] . 中国癌症杂志 , 2021 , 31 ( 7 ): 589 - 595 .

DING G F , GUO L M , LU Y F . The relationship between expressions of HER2 and BRCA1 and radiotherapy sensitivity in breast cancer patients [J ] . China Oncol , 2021 , 31 ( 7 ): 589 - 595 .

李贺 . 非小细胞肺癌患者癌组织中BRCA1和p53表达与放疗敏感性的相关性 [J ] . 临床医学 , 2023 , 43 ( 2 ): 1 - 4 .

LI H . Correlation of BRCA1 and p53 expression in cancer tissues with radiosensitivity in patients with non-small cell lung cancer [J ] . Clin Med , 2023 , 43 ( 2 ): 1 - 4 .

SEYNAEVE C , VERHOOG L C , VAN DE BOSCH L M , et al . Ipsilateral breast tumour recurrence in hereditary breast cancer following breast-conserving therapy [J ] . Eur J Cancer , 2004 , 40 ( 8 ): 1150 - 1158 .

BERNSTEIN J L , THOMAS D C , SHORE R E , et al . Contralateral breast cancer after radiotherapy among BRCA 1 and BRCA 2 mutation carriers: a WECARE study report [J ] . Eur J Cancer , 2013 , 49 ( 14 ): 2979 - 2985 . DOI: 10.1016/j.ejca.2013.04.028 http://doi.org/10.1016/j.ejca.2013.04.028 https://linkinghub.elsevier.com/retrieve/pii/S0959804913003626 https://linkinghub.elsevier.com/retrieve/pii/S0959804913003626

BROEKS A , BRAAF L M , HUSEINOVIC A , et al . Identification of women with an increased risk of developing radiation-induced breast cancer: a case only study [J ] . Breast Cancer Res , 2007 , 9 ( 2 ): R26 . DOI: 10.1186/bcr1668 http://doi.org/10.1186/bcr1668

Views

2026

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Expert consensus on population-based BRCA germline mutation screening in China (2024 edition)

New concept of de-escalation management strategy in breast cancer patients with 1-2 positive sentinel lymph nodes

Progression of adjuvant radiotherapy upon breast cancer immunity

Guidelines for breast cancer diagnosis and treatment by China Anti-Cancer Association (2026 edition)

Progress and prospects of CENPA-driven chromosomal instability in breast cancer: mechanisms, prognostic implications, and therapeutic perspectives

Related Author

Anti-Cancer Association Tumor Biomarker Professional Committee China

Anti-Cancer Association Tumor Biomarker Professional Committee Shanghai

Zhao BI

Yongsheng WANG

王小方

郭小毛

The Society of Breast Cancer China Anti-Cancer Association

Breast Oncology Group of the Oncology Branch of the Chinese Medical Association

Related Institution

Department of Breast Cancer Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences

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

Department of Breast Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College

Department of Breast Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital& Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College

Department of Cancer Prevention, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University

AI问答

⁰

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

DOI：10.19401/j.cnki.1007-3639.2024.02.006

摘要

Abstract

关键词

Keywords

references