乳腺癌临床病理特征和分子分型对新辅助化疗疗效及预后的预测价值

Value of molecular classification and clinicopathological features to predicting neoadjuvant chemotherapy effect and prognosis of breast cancer

目的探讨乳腺癌临床病理特征和分子分型对新辅助化疗(neoadjuvantchemotherapy,NCT)疗效和预后的预测价值。方法浸润性乳腺癌患者158例,采用免疫组织化学方法检测癌组织中雌激素受体(estrogenreceptor,ER)、孕激素受体(progesteronereceptor,PR)、人表皮生长因子受体-2(humanepidermalgrowthfactorreceptor-2,HER-2)及Ki-67表达情况;4个周期NCT后行乳腺癌改良根治术或保乳手术,分析病理完全缓解(pathologiccompleteresponse,pCR)与临床病理特征的关系。绘制ROC曲线,分析Ki-67对NCT疗效及无远处转移生存、总生存期的预测价值;采用Kaplan-Meier生存曲线评估不同Ki-67表达量及分子分型患者的无复发生存率。结果158例患者肿瘤组织Ki-67阳性表达率>14%、ER阴性、PR阴性者pCR率(24.4%、37.9%、33.3%)高于Ki-67阳性表达率≤14%及ER阳性和PR阳性患者(7.4%、9.8%、7.1%)(P<0.05),不同分子分型中HER-2阳性型(45.7%)、三阴性乳腺癌型(29.2%)、Luminal-A型(20.0%)、Luminal-B型(10.1%)患者pCR率依次降低(P<0.05);当Ki-67阳性表达率最佳截断值为37.50%时,预测NCT疗效的AUC为0.766,其敏感度为85.3%,特异度为60.5%(P<0.05);当Ki-67阳性表达率最佳截断值为42.5%时,预测无远处转移生存、总生存期的AUC分别为0.774、0.792,灵敏度为72.7%、78.6%,特异度为74.1%、75.7%(P<0.05);Ki-67阳性表达率>30%的患者无复发生存率(84.0%)低于Ki-67阳性表达率≤30%的患者(97.0%)(P<0.05),不同分子分型患者无复发生存率比较差异均无统计学意义(P>0.05)。结论Ki-67阳性表达率高的乳腺癌患者化疗疗效更好、预后更差,而ER、PR及不同分子分型也可作为NCT疗效的预测因子。

Objective To study the value of clinicopathological features and molecular classification to the prediction of therapeutic effect and prognosis of neoadjuvant chemotherapy(NCT) for breast cancer. Methods Immunohistochemistry method was used to detect the levels of estrogen receptor(ER), progesterone receptor(PR), human epidermal growth factor receptor-2(HER-2) and Ki-67 in 158 patients with invasive breast cancer. After 4 cycles of NCT, all patients received modified radical mastectomy or breast-conserving surgery. The relationship between pathologic complete response(pCR) and clinicopathological features was analyzed. ROC was drawn to analyze the value of Ki-67 to predicting the therapeutic effect of NCT, distant metastasis free survival and overall survival. Kaplan-Meier curve was used to assess the recurrence-free survival rates in patients with various Ki-67 levels and molecular classifications. Results In 158 patients, pCR rates were significantly higher in patients with Ki-67 >14%, ER negative and PR negative(24.4%, 37.9%, 33.3%) than those in patients with Ki-67 ≤14%, ER positive and PR positive(7.4%, 9.8%, 7.1%)(P<0.05), and pCR rate decreased in turn in patients with HER-2 positive(45.7%), triple negative breast cancer(29.2%), Luminal-A type(20.0%) and Luminal-B type(10.1%)(P<0.05). When the optimal cut-off of Ki-67 was 37.50%, the AUC for NCT was 0.766, the sensitivity was 85.3%, and the specificity was 60.5%(P<0.05). When the optimal cut-offof Ki-67 was 42.5%,the AUCvalues for distant metastasisfree survival and overall survival were 0.774 and 0.792,respectively,the sensitivities were 72.7% and 78.6%,and the specificities were 74.1% and 75.7%,respectively(P<0.05).The recurrence-free survival rate was significantly lower in patients with Ki-67>30%(84.0%)than that in patients with Ki-67≤30%(97.0%)(P<0.05),and showed no significant difference among patients with different molecular classifications(P>0.05).Conclusion Patients with high expression of Ki-67 have better chemotherapy efficacy and worse prognosis,while ER,PR and different molecular classification could be used as predictors for chemotherapy effect.