中国癌症杂志 ›› 2021, Vol. 31 ›› Issue (7): 589-595.doi: 10.19401/j.cnki.1007-3639.2021.07.005

• 论著 • 上一篇    下一篇

乳腺癌患者HER2和BRCA1表达与放疗敏感性的关系研究

丁高峰,郭雷鸣,陆寓非   

  1. 郑州大学附属肿瘤医院放疗科,河南 郑州 450000
  • 出版日期:2021-07-30 发布日期:2021-08-04
  • 通信作者: 郭雷鸣 E-mail: guoguo19801128@163.com
  • 基金资助:
    国家自然科学基金青年项目(82004090);河南省博士后科研项目(19030074)。

The relationship between expressions of HER2 and BRCA1 and radiotherapy sensitivity in breast cancer patients

DING Gaofeng, GUO Leiming, LU Yufei   

  1. Department of Radiotherapy, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450000, Henan Province, China
  • Published:2021-07-30 Online:2021-08-04
  • Contact: GUO Leiming E-mail: guoguo19801128@163.com

摘要: 背景与目的:乳腺癌是全球最常见的女性恶性肿瘤,且发病率仍在不断上升。乳腺癌的术后放疗可有效地改善局部控制率和长期生存率,放疗已成为乳腺癌治疗的主要技术。如何进一步减少患者正常组织的不良反应、提高放疗效果成为研究热点。探讨人表皮生长因子受体2(human epidermal growth factor receptor 2,HER2)和乳腺癌易感基因1(breast cancer susceptibility gene 1,BRCA1)在乳腺癌患者中的表达,并研究两者的表达与放疗敏感性的相关性,以期为临床治疗提供依据。方法:回顾并分析郑州大学附属肿瘤医院收治的156例乳腺癌患者的癌变组织和相邻正常乳腺组织的临床资料,并选取145例乳腺良性病变患者的良性乳腺病变组织作为对照。采用实时荧光定量聚合酶链反应(real-time fluorescence quantitative polymerase chain reaction,RTFQ-PCR)检测组织中HER2和BRCA1 mRNA表达,采用免疫组织化学法检测组织中HER2和BRCA1蛋白的水平。采用Spearman相关性分析HER2和BRCA1蛋白表达的关系,采用Kaplan-Meier生存分析评估乳腺癌术后放疗患者的生存率,探讨HER2和BRCA1表达与乳腺癌放疗患者预后的关系。结果:与相邻正常乳腺组织和良性乳腺病变组织相比,癌变组织HER2 mRNA和蛋白的表达上调(P<0.01),BRCA1 mRNA和蛋白表达下降(P<0.01)。放疗后,HER2阳性患者的局部失败率明显高于阴性患者(P<0.05),BRCA1阳性的局部失败率则明显低于阴性患者(P<0.01)。HER2阳性患者的5年生存率明显低于HER2阴性患者(P<0.01),BRCA1阳性患者的5年生存率则明显高于BRCA1阴性患者(P<0.01)。结论:高表达HER2和低表达BRCA1基因的乳腺癌患者对放疗的敏感性较低,为乳腺癌患者的临床治疗提供了新的理论依据。

关键词: 乳腺癌, 人表皮生长因子受体2, 乳腺癌易感基因1, 放疗敏感性, 局部失败率

Abstract: Background and purpose: Breast cancer is the most common malignancy in women worldwide, and its incidence continues to rise. Postoperative radiotherapy for breast cancer can effectively improve local control rate and long-term survival rate. Radiotherapy has become the main technique for breast cancer treatment. How to further reduce the adverse reactions of patients’ normal tissues and improve the curative effect of radiotherapy has become the research focus. This study aimed to investigate the expressions of human epidermal growth factor receptor 2 (HER2) and breast cancer susceptibility gene 1 (BRCA1) in breast cancer patients, and to study the correlation between their expressions and radiation sensitivity, so as to provide the experimental foundation for clinical treatment research. Methods: Breast cancer tissues and adjacent normal breast tissues of 156 breast cancer patients treated in Affiliated Cancer Hospital of Zhengzhou University were collected in this retrospective cohort study, and the tissues of 145 patients with benign breast disease were selected as the control. Real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) was used to detect the expressions of HER2 and BRCA1 in tissues. Immunohistochemistry was used to test the HER2 and BRCA1 protein expressions in tissues. Relationships of HER2 and BRCA1 expressions with radiation sensitivity and prognosis of breast cancer patients were assessed by Spearman correlation analysis and Kaplan-Meier survival analysis. Results: Compared with the adjacent normal breast tissues and benign breast lesion tissues, breast cancer tissues had high expressions of HER2 mRNA and protein and low expressions of BRCA1 mRNA and protein (P<0.01). After radiotherapy, the local failure rate of HER2 positive patients was significantly higher compared with the HER2 negative patients (P<0.05), while that of BRCA1 positive patients was significantly lower compared with the negative group (P<0.01). The survival time of HER2 positive patients was significantly shorter compared with the HER2 negative patients, while that of BRCA1 positive patients was significantly longer compared with the BRCA1 negative patients (P<0.01). Conclusion: The breast cancer patients with high HER2 gene expression and low BRCA1 gene expression are less sensitive to radiotherapy, providing a new theoretical basis for the clinical treatment of breast cancer patients.

Key words: Breast cancer, Human epidermal growth factor receptor 2, Breast cancer susceptibility gene 1, Radiation sensitivity, Local failure rate