曲妥珠单抗对HER-2阳性早期乳腺癌骨髓微转移的影响

Effects of Trastuzumab on bone marrow micrometastases in HER-2 positive early breast cancer

目的:检测HER-2阳性的早期乳腺癌患者应用曲妥珠单抗(Trastuzumab)治疗前后骨髓微转移的改变,探讨HER-2基因及Herceptin对骨髓微转移的影响。方法:应用实时定量逆转录-聚合酶链反应(qRT-PCR)方法检测15例HER-2阳性乳腺癌及18例HER-2阴性乳腺癌患者术前及化疗后骨髓CK19的表达水平,其中10例HER-2阳性乳腺癌患者在化疗结束后,继续应用Herceptin治疗,3月后再次抽取骨髓标本,qRT-PCR检测CK19的表达水平。结果:手术前,14例HER-2阳性乳腺癌患者骨髓CK19表达阳性(93.3%),而HER-2阴性患者8例CK19表达阳性(44.4%),二者差异显著(P=0.000)。化疗后,12例HER-2阳性乳腺癌患者CK19表达阳性(80.0%),而HER-2阴性患者3例表达阳性(16.7%),二者差异显著(P=0.000)。10例HER-2阳性乳腺癌患者化疗后继续应用Herceptin治疗3月后,骨髓CK19的表达明显下降(102.78±98.24 vs 66.92±49.18,P=0.036)。结论:HER-2基因的表达与早期乳腺癌患者骨髓微转移密切相关,而Herceptin可以降低骨髓微转移病灶,提示骨髓微转移情况可以作为Herceptin治疗疗效的早期预测指标。

Objective：To explore the variation of bone marrow micrometastases in HER-2 positive early breast cancer before and after Trastuzumab therapy and the effects of Trastuzumab on bone marrow micrometastases.Methods：CK19 mRNA in bone marrow was detected by qRT-PCR as an index of micrometastases in 15 cases of HER-2 positive breast cancer and 18 HER-2 negative breast cancer preoperation and post-chemotherapy.10 cases of HER-2 positive breast cancer continued Trastuzumab therapy and then were detected again for CK19 mRNA 3 months later.Results： CK19 mRNA was found in bone marrow of 14 cases of HER-2 positive and 8 cases of HER-2 negative breast cancer preoperation.There was a significant difference between the two groups（P=0.000）.After 6 cycle＇s adjuvant chemotherapy,CK19 positive rates in HER-2 positive and HER-2 negative breast cancer were 80.0% and 16.7%,respectively.Significant difference between the two groups was found（P=0.000）.After 3 months Trastuzumab therapy,expression of CK19 mRNA declined significantly in 10 cases of HER-2 positive breast cancer（102.78±98.24 vs 66.92±49.18,P=0.036）.Conclusion：Bone marrow micrometastases correlate with HER-2 gene expression.Trastuzumab,a monoclonal antibody for HER-2,can reduce the bone marrow micrometastases in breast cancer.Thus bone marrow micrometastases may be a predictive factor for early effects of Trastuzumab therapy.