Prognostic value of Ki67 expression after short-term presurgical endocrine therapy for primary breast cancer
Prognostic value of Ki67 expression after short-term presurgical endocrine therapy for primary breast cancer
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DOI：
10.1093/jnci/djk020
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发表时间：
2007-01-17
影响因子：
10.3
通讯作者：
Walsh, Geraldine
中科院分区：
文献类型：
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作者：
Dowsett, Mitch;Smith, Ian E.;Walsh, Geraldine
肿瘤中增殖抗原Ki67的表达被广泛用于评估肿瘤患者的预后。患者短期暴露于治疗药物后Ki67表达的变化经常被用作药效的药效学标记，特别是在接受手术前的乳腺癌患者中。为了确定乳腺癌内分泌治疗过程中肿瘤细胞增殖水平的临床意义，我们对158例激素受体阳性的原发疾病患者，在术前阿那曲唑或他莫昔芬或阿那曲唑联合他莫昔芬治疗前后2周的肿瘤活检标本中Ki67的表达进行了检测。在一项多变量分析中，我们发现在内分泌治疗2周后较高的Ki67表达与较低的无复发生存率有统计学意义（P = 0.004），而基线时较高的Ki67表达则无统计学意义。治疗2周后，基线肿瘤大小越大、雌激素受体水平越低，无复发生存率越低，差异均有统计学意义（P < 0.001, P = 0.04）。我们的数据表明，测量短期内分泌治疗后的肿瘤Ki67水平可以通过整合基线Ki67水平的预后价值和与治疗获益相关的Ki67水平变化来改善无复发生存的预测。
Tumor expression of the proliferation antigen Ki67 is widely used to assess the prognosis of cancer patients. A change in the expression of Ki67 after short-term exposure of patients to therapeutic agents is frequently used as a pharmacodynamic marker of efficacy, particularly among breast cancer patients before undergoing surgery. To determine the clinical significance of the level of tumor cell proliferation during endocrine therapy for breast cancer, we measured the expression of Ki67 in tumor biopsy samples taken before and after 2 weeks of presurgical treatment with anastrozole or tamoxifen or the combination of anastrozole plus tamoxifen in 158 patients with hormone receptor-positive primary disease. In a multivariable analysis, we found that higher Ki67 expression after 2 weeks of endocrine therapy was statistically significantly associated with lower recurrence-free survival (P = .004) whereas higher Ki67 expression at baseline was not. Larger baseline tumor size and lower estrogen receptor level after 2 weeks of treatment were also statistically significantly associated with poorer recurrence-free survival (P < .001 and P = .04, respectively). Our data indicate that measurements of tumor Ki67 level after short-term endocrine treatment may improve the prediction of recurrence-free survival by integrating the prognostic value of Ki67 level at baseline with changes in Ki67 level that are associated with treatment benefit.