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中华损伤与修复杂志(电子版)

中华损伤与修复杂志(电子版) ›› 2017, Vol. 12 ›› Issue (02) : 113 -117. doi: 10.3877/cma.j.issn.1673-9450.2017.02.008

所属专题： 文献；

论著

新辅助化疗对浸润性乳腺癌分子标志物及分子分型的影响
陈圣1, 黄焰2, 王也3, 柳伟伟4, 张建华1, 王怀涛5, 董茂盛1,†()   
  1. 1. 100088　北京，火箭军总医院普通外科
    2. 100071　北京，军事医学科学院附属医院乳腺外科
    3. 100029　北京，中日友好医院病理科
    4. 100850　军事医学科学院统计学教研室
    5. 100071　北京，军事医学科学院附属医院病理科
  • 收稿日期:2016-12-26 出版日期:2017-04-01
  • 通信作者: 董茂盛

Research of relationship between the change of molecular marker of breast cancer after neoadjuvant chemotherapy and therapeutic effect

Sheng Chen1, Yan Huang2, Ye Wang3, Weiwei Liu4, Jianhua Zhang1, Huaitao Wang5, Maosheng Dong1,†()   

  1. 1. Department of General Surgery, the General Hospital of the PLA Rocket Force, Beijing 100088, China
    2. Department of Breast Surgery, Affiliated Hospital of Academy of Military Medical Sciences, Beijing 100071, China
    3. Department of Pathology, China-Japan Friendship Hospital, Beijing 100029, China
    4. Department of Statistics, Academy of Military Medical Sciences, Beijing 100850, China
    5. Department of Pathology, Affiliated Hospital of Academy of Military Medical Sciences, Beijing 100071, China
  • Received:2016-12-26 Published:2017-04-01
  • Corresponding author: Maosheng Dong
  • About author:
    Corresponding author: Dong Maosheng, Email:
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引用本文：

陈圣, 黄焰, 王也, 柳伟伟, 张建华, 王怀涛, 董茂盛. 新辅助化疗对浸润性乳腺癌分子标志物及分子分型的影响[J]. 中华损伤与修复杂志(电子版), 2017, 12(02): 113-117.

Sheng Chen, Yan Huang, Ye Wang, Weiwei Liu, Jianhua Zhang, Huaitao Wang, Maosheng Dong. Research of relationship between the change of molecular marker of breast cancer after neoadjuvant chemotherapy and therapeutic effect[J]. Chinese Journal of Injury Repair and Wound Healing(Electronic Edition), 2017, 12(02): 113-117.

目的

研究乳腺癌新辅助化疗(NAC)(蒽环类联合紫衫类)过程中，雌激素受体(ER)、孕激素受体(PR)、HER2状态和Ki67值的变化，以及这些变化是否会对分子分型产生影响。

方法

回顾性分析从2011年11月到2015年6月期间在军事医学科学院附属医院行蒽环联合紫衫类NAC的137例浸润性乳腺癌患者。通过免疫组织化学方法测定NAC前后组织中ER、PR、HER2以及Ki67，并分为：Luminal A、Luminal B、三阴性和HER2阳性4种分子亚型。NAC前后分子标志物和分子分型的变化采用χ2检验或用Fisher确切概率法检验，并用Kappa检验对新辅助化疗前后的分子标志物及分子分型进行一致性检验。

结果

NAC前后ER、PR、HER2、Ki67的一致率分别为88.32%、83.21%、94.16%和75.91%。ER、PR、HER2在NAC前后变化差异均无统计学意义(P值均大于0.05)。在NAC后Ki67值平均数从35.75%降到了19.12%(P<0.05)。除性激素受体(HR)阳性，HER2阴性型的肿瘤之外，其余病例的分子分型在NAC前后的结果一致(P＝0.488)。NAC前后分子分型的一致率为57.66%，Kappa值＝0.4020。

结论

NAC会使浸润性乳腺癌Ki67的表达下降，并会影响HR阳性、HER2阴性型肿瘤的分子分型。

关键词: 乳腺肿瘤, 新辅助治疗, 雌激素受体, 孕激素受体, HER2
Objective

To research whether the changes of estrogen receptor (ER) , progesterone receptor (PR), HER2 associate with the efficacy, during the course of neoadjuvant chemotherapy(NAC)(anthracycline and docetaxel), and to research whether these changes will affect the molecular subtypes.

Methods

One hundred and thirty seven cases of patients given NAC (anthracycline and docetaxel) were retrospectively analyzed from November 2011 to June 2015 in the Affiliated Hospital of Academy of Military Medical Sciences. ER, PR, HER2 and Ki67 expression were tested by immunohistochemistry.According to immunohistochemistry results, the cases were divided into 4 molecular subtypes: Luminal A, Luminal B, triple negative and HER2 positive. Changes of ER, PR, HER2 and Ki67 expression and molecular subtypes after neoadjuvant chemotherapy were tested by Chi-square test and Fisher′s exact test, and Kappa test was used to test the consistency of molecular markers and molecular subtypes before and after NAC.

Results

Concordance rate of ER, PR, HER2 and Ki67 were 88.32%, 83.21%, 94.16% and 75.91 respectively.There was no significant difference in ER, PR and HER2 before and after NAC(P values were all more than 0.05). Ki67 average value had fallen from 35.75% to 19.12% after NAC(P<0.05). Molecular subtypes would haven not been changed after NAC, except for cases with Hormone receptors(HR)positive and HER2 negative (P=0.488). Concordance rate of molecular subtypes between pre-NAC biopsies and post-NAC specimens was 57.66% (Kappa=0.4020).

Conclusion

NAC leads to a decrease of Ki67 value in invasive breast cancer cases, and makes an effect on tumors with molecular subtype of HR+ , HER2-.

Key words: Breast neoplasms, Neoadjuvant therapy, Receptors, Estrogen, Receptors, Progesterone, Genes, erbB-2
表1 浸润性乳腺癌患者NAC前后的病理特征(例)
时间 ER PR HER2 Ki67
阳性 阴性 阳性 阴性 阳性 阴性 ≤14% >14%
NAC前 101 36 84 53 10 127 33 104
NAC后 99 38 77 60 7 130 99 38
χ2值 0.095 1.182 0.352 13.234
P值 0.786 0.390 0.564 <0.05
时间 HR 分子分型
阳性 阴性 Luminal A LuminalB HER2- Luminal B HER2＋ 三阴性 HER2阳性
NAC前 106 31 54 46 7 26 4
NAC后 103 34 92 10 3 28 4
χ2值 0.235 34.707
P值 0.670 <0.01
表2 浸润性乳腺癌患者NAC前后分子标志物变化一致性的比较
NAC前 NAC后(例) 一致率(%) McNemar χ 2检验 Kappa值 P值
阴性 阳性
ER ? ? 88.32 0.6171 0.7039 <0.01
? 阴性 29 7 ? ? ? ?
? 阳性 9 92 ? ? ? ?
PR ? ? 83.21 0.1444 0.6526 <0.01
? 阴性 44 8 ? ? ? ?
? 阳性 15 70 ? ? ? ?
HER2 ? ? 94.16 0.1573 0.5260 <0.01
? 阴性 124 2 ? ? ? ?
? 阳性 6 5 ? ? ? ?
Ki67 ? ? 75.91 <0.01 0.5272 <0.01
? ≤14% 63 2 ? ? ? ?
? >14% 31 41 ? ? ? ?
HR ? ? 92.70 0.5271 0.7962 <0.01
? 阴性 27 4 ? ? ? ?
? 阳性 6 100 ? ? ? ?
表3 浸润性乳腺癌患者NAC前后4个分子亚型的一致性比较
NAC前 NAC后(例) 一致率(%) Kappa值 P值
Luminal A Luminal B 三阴性 HER2阳性
Luminal A 33 2 0 0 ? ? ?
Luminal B 44 24 4 0 57.66 0.4020 <0.01
三阴性 3 1 20 2 ? ? ?
HER2阳性 0 1 1 2 ? ? ?
表4 浸润性乳腺癌患者NAC前后5个分子亚型的一致性比较
NAC前 NAC后(例) 一致率(%) Kappa值 P值
Luminal A Luminal B HER2－ Luminal B HER2＋ 三阴性 HER2阳性
Luminal A 33 2 0 0 0 ? ? ?
Luminal B HER2－ 42 20 0 2 0 ? ? ?
Luminal B HER2＋ 2 2 2 2 0 56.2 0.3893 <0.01
三阴性 3 1 0 20 2 ? ? ?
HER2阳性 0 0 1 1 2 ? ? ?
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