刘婧思, 陈久安, 孙洁, 姚璐, 张娟, 解云涛, 徐晔. DNA损伤修复基因胚系突变乳腺癌新辅助化疗疗效分析[J]. 中国肿瘤临床, 2023, 50(10): 497-503. DOI: 10.12354/j.issn.1000-8179.2023.20230054
引用本文: 刘婧思, 陈久安, 孙洁, 姚璐, 张娟, 解云涛, 徐晔. DNA损伤修复基因胚系突变乳腺癌新辅助化疗疗效分析[J]. 中国肿瘤临床, 2023, 50(10): 497-503. DOI: 10.12354/j.issn.1000-8179.2023.20230054
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Jingsi Liu, Jiuan Chen, Jie Sun, Lu Yao, Juan Zhang, Yuntao Xie, Ye Xu. Efficacy analysis of neoadjuvant chemotherapy regimens for patients with breast cancer carrying germline mutations in DNA damage repair genes[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2023, 50(10): 497-503. DOI: 10.12354/j.issn.1000-8179.2023.20230054
Citation: Jingsi Liu, Jiuan Chen, Jie Sun, Lu Yao, Juan Zhang, Yuntao Xie, Ye Xu. Efficacy analysis of neoadjuvant chemotherapy regimens for patients with breast cancer carrying germline mutations in DNA damage repair genes[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2023, 50(10): 497-503. DOI: 10.12354/j.issn.1000-8179.2023.20230054
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DNA损伤修复基因胚系突变乳腺癌新辅助化疗疗效分析

Efficacy analysis of neoadjuvant chemotherapy regimens for patients with breast cancer carrying germline mutations in DNA damage repair genes

    摘要
  • 摘要:
      目的   分析携带DNA损伤修复（DNA damage repair，DDR）相关基因突变的乳腺癌患者对基础蒽环类新辅助化疗方案（anthracycline，A）、蒽环联合紫杉类新辅助化疗方案（anthracycline-taxane，A-T）、蒽环联合紫杉和铂类新辅助化疗方案（anthracycline-taxane/carboplatin，A-TP）的疗效反应。
      方法  2003年10月至2015年5月，105例携带DDR基因胚系突变（非BRCA）的原发性乳腺癌患者在北京大学肿瘤医院分别接受A（n=69）、A-T（n=19）、A-TP（n=17）3种新辅助化疗方案。通过χ2检验或Fisher精确检验比较3组患者的病理完全缓解（pathological complete remission，pCR）率；采用Kaplan-Meier生存分析和Cox回归模型分析患者的乳腺癌特异生存（breast cancer-specific survival，BCSS）及无复发生存（recurrence-free survival，RFS）。
      结果  93.3%（98/105）的患者接受了4～8个周期的新辅助化疗。接受A、A-T、A-TP新辅助方案的3组患者的pCR率分别为11.6%、21.1%和35.3%。A-TP组pCR率显著高于A组（P=0.028），A-TP组pCR率也高于A-T组，但未达到统计学差异。经过65.6个月的中位随访， A-TP组的BCSS（HR=0.50，95%CI：0.09～2.73，P=0.41）和RFS（HR=0.51，95%CI：0.15～1.74，P=0.27）略优于A-T组，但无统计学差异。
      结论   DDR基因胚系突变患者应用A-TP新辅助化疗方案可显著提高pCR率，加入铂类药物或可提高患者的药物反应性及预后 。

     

    Abstract:
      Objective  To explore the efficacy of anthracycline(A), anthracycline-taxane (A-T), and anthracycline-taxane/carboplatin (A-TP) neoadjuvant chemotherapy regimens in patients with breast cancer harboring germline mutations in DNA damage repair (DDR) genes.
      Methods  A total of 105 patients with operable primary breast cancer, carrying germline mutations in any of the 15 DDR genes, were given neoadjuvant treatment in Peking University Cancer Hospital & Institute from October 2003 to May 2015. Among them, 69, 19, and 17 patients received the neoadjuvant regimens A, A-T, and A-TP, respectively. The pathological complete remission (pCR) rates of the three groups to the neoadjuvant chemotherapy were compared by χ2 or Fisher’s exact test. The Kaplan-Meier survival analysis and Cox proportional hazards model were used to determine the breast cancer-specific survival (BCSS) and recurrence-free survival (RFS) rates in patients with breast cancer.
      Results  93.3% of patients received four to eight cycles of neoadjuvant chemotherapy. The respective pCR rates of the A, A-T, and A-TP groups were 11.6%, 21.1%, and 35.3%. The pCR rate of the A-TP group was significantly higher than that of the A group (P=0.028). The A-TP group also displayed a better pCR rate relative to that of the A-T group, but the difference was not statistically significant. After a median follow-up of 65.6 months, DDR gene mutation carriers treated with the A-TP regimen exhibited better BCSS (hazard ratio HR=0.50, 95% confidence interval CI: 0.09–2.73, P=0.41) and RFS (HR=0.51, 95%CI: 0.15–1.74, P=0.27) than patients treated with the A-T regimen; however, the variation did not reach the significance threshold.
      Conclusions  Results of this study suggested that patients with germline mutations in DDR genes can achieve higher pCR rates when carboplatin is added to the standard A-T-based neoadjuvant chemotherapy. The A-TP regimen also showed a trend towards better prognosis compared with the A regimen.

     

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