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中华乳腺病杂志(电子版)

中华乳腺病杂志(电子版) ›› 2010, Vol. 04 ›› Issue (06) : 712 -720. doi: 10.3877/cma.j.issn.1674-0807.2010.06.014

临床研究

乳腺癌生物标记物表达水平对新辅助化疗疗效的预测价值
张弛1, 段学宁1,†()   
  1. 1.100034 北京,北京大学第一医院乳腺疾病中心
  • 收稿日期:2009-03-09 出版日期:2010-12-01
  • 通信作者: 段学宁

Clinical value of molecular markers predicting the response of breast cancer to neoadjuvant chemotherapy

Chi ZHANG1, Xue-ning DUAN†,1()   

  1. 1.Breast Disease Centre,First Hospital,Peking University,Beijing 100034 China
  • Received:2009-03-09 Published:2010-12-01
  • Corresponding author: Xue-ning DUAN
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张弛, 段学宁. 乳腺癌生物标记物表达水平对新辅助化疗疗效的预测价值[J/OL]. 中华乳腺病杂志(电子版), 2010, 04(06): 712-720.

Chi ZHANG, Xue-ning DUAN. Clinical value of molecular markers predicting the response of breast cancer to neoadjuvant chemotherapy[J/OL]. Chinese Journal of Breast Disease(Electronic Edition), 2010, 04(06): 712-720.

目的

探讨乳腺癌生物标记物雌激素受体(ER)、人类表皮生长因子受体-2(HER-2)、P53和Ki67的表达与新辅助化疗疗效之间的关系。

方法

对2007年10月至2009年9月在北京大学第一医院乳腺疾病中心接受4～6个周期紫杉类联合蒽环类方案新辅助化疗的165例乳腺癌患者资料进行回顾性分析。用免疫组织化学方法检测新辅助化疗前肿瘤病灶ER、HER-2、P53和Ki67的表达情况,用术后病理评价新辅助化疗疗效,病理学反应级别为G4、G5则认为化疗有效。用四格表资料的χ2 检验法分析上述指标与新辅助化疗疗效之间的关系。

结果

165例患者中56.4%(93/165)新辅助化疗有效。ER 阳性者有效率为43.5%(20/46),ER 阴性者有效为61.3%(73/119),两组之间差异有统计学意义(χ2=4.31,P=0.04);HER-2 过表达者有效率为72.0%(36/50),低表达者为49.6%(57/115),二者差异有统计学意义(χ2=7.13,P=0.01);P53阳性者有效率为66.7%(30/45),阴性者为53.4%(47/88),两组间差异无统计学意义(χ2=2.15,P=0.14);Ki67过表达者化疗有效率为62.4%(68/109),低表达者为44.0%(22/50),两组间差异有统计学意义(χ2=4.72,P=0.03)。

结论

ER 阴性、HER-2及Ki67过表达者对紫杉联合蒽环方案的新辅助化疗更敏感,ER、HER-2及Ki67表达情况对新辅助化疗疗效有预测作用。

关键词: 雌激素受体, 人类表皮生长因子受体-2, P53, Ki67, 新辅助化疗, 乳腺肿瘤

Objective

To investigate the relationship between the expressions of estrogen receptor(ER),human epidermal growth factor receptor-2(HER-2),P53 and Ki67 and the therapeutic effect of neoadjuvant chemotherapy for breast cancer.

Methods

One hundred and sixty-five patients treated with 4～6 cycles of neoadjuvant taxanes and anthracyclines chemotherapy in our centre between Oct 2007 and Sep 2009 were included in this retrospective study.The expressions of ER,HER-2,P53 and Ki67 were detected by immunohistochemistry method before neoadjuvant chemotherapy.We used pathology to evaluate the therapeutic effectiveness and considered G4 and G5 as efficiency.Fourfold table Chi squaretest was used to analyze the relationship between the features above and the therapeutic effectiveness.

Results

The overall efficiency rate of neoadjuvant chemotherapy among the 165 patients was 56.4% (93/165).The efficiency rate was 43.5%(20/46)for ER positive patients,and 61.3%(73/119)for ER negative patients;the difference between the two groups was significant(χ2=4.31;P=0.04).HER-2 over-expressed patients achieved efficiency rate of 72.0%(36/50),and HER-2 lowly expressed patients 49.6% (57/115),with significant difference between the two groups(χ2=7.13,P=0.01).The efficiency rate was 66.7%(30/45)for P53 positive patients,and 53.4%(47/88)for negative patients,with no significant difference between the two groups(χ2=2.15,P=0.14).Ki67 over-expressed patients acquired 62.4% (68/109)efficiency rate,and the lowlyexpressed ones 44.0%(22/50),with statistical difference(χ2=4.72,P=0.03).

Conclusions

The results manifest that ER negative,HER-2 over-expressed and Ki67 over-expressed patients are more susceptive to neoadjuvant taxanes plus anthracyclines chemotherapy.The expression status of ER,HER-2 and Ki67 can well predict the efficiency of neoadjuvant chemotherapy.

Key words: Estrogen receptor, Human epidermal growth factor receptor-2, P53, Ki67, Neoadjuvant chemotherapy, Breast neoplasms
图1 雌激素受体阳性患者的免疫组织化学检测结果(Envision染色 ×200)
图2 雌激素受体阴性患者的免疫组织化学检测结果(Envision染色 ×200)
图3 人类表皮生长因子受体-2过表达患者的免疫组织化学检测结果(Envision染色 ×200)
图4 人类表皮生长因子受体-2低表达患者的免疫组织化学检测结果(Envision染色 ×200)
图5 Ki67过表达患者的免疫组织化学检测结果(Envision染色 ×200)
图6 Ki67低表达患者的免疫组织化学检测结果(Envision染色 ×200)
图7 P53阳性患者的免疫组织化学检测结果(Envision染色 ×200)
图8 P53阴性患者的免疫组织化学检测结果(Envision染色 ×200)
表1 新辅助化疗前ER、HER-2、P53和Ki67的表达与化疗疗效的关系(例)
疗效 ER HER-2 P53 Ki67
阳性 阴性 过表达 低表达 阳性 阴性 过表达 低表达
有效 20 73 36 57 30 47 68 22
无效 26 46 14 58 15 41 41 28
χ 2值 4.31 7.13 2.15 4.72
P值 0.04 0.01 0.14 0.03
图9 新辅助化疗前ER、HER-2、P53和Ki67的表达与化疗疗效的关系 a:雌激素受体(ER)阳性;b:ER 阴性;c:人类表皮生长因子受体-2(HER-2)过表达;d:HER-2低表达;e:P53阳性;f:P53阴性;g:Ki67过表达;h:Ki67低表达
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