乳腺癌生物标志物表达状态的时间变异性

目的 探讨乳腺癌患者复发前后HER-2和激素受体表达是否存在时间变异性。方法 收集168例长期随访（>5年）的乳腺癌患者不同时间点的组织标本，并通过免疫组织化学进行HER-2、ER和PR检测，比较不同时间点上述生物标志的差异，同时分析与患者原始治疗和复发后治疗的关系。结果 168例乳腺癌患者中，36例复发，对其中27例复发组织标本进行检测。发现5例患者出现HER-2表达状态的变化，其中3例HER-2下调，2例上调；7例出现ER变化：5例ER表达下调，2例ER表达上调。2例出现PR下调。HER-2的表达变化与复发前放化疗无明显联系，但抗激素治疗导致HR表达下调，激素受体变化对随后的化疗治疗效果稍差（76% vs. 88%，P=0.21），无疾病进展时间相似（33.4月vs. 38.60月，Log-rank=1.96，P=0.16）。结论 乳腺癌患者HER-2和激素受体的表达可以随时间变异，复发患者需要再次检测上述生物标志。

Changes in Biological Marker Status During Breast Cancer Progression

Objective To evaluate the biological marker status during breast cancer progression for long-term survival patients with breast cancer in China. Methods One hundred and sixty-eight breast cancer patients with a long-term follow up time (more than 5 years) were collected. The tissue samples from 27 patients with metachronous recurrence were obtained. HER-2, ER and PR status were detected by immunohistochemistry or Her-2 gene amplification by fluorescence in situ hybridization. The relationships between HER 2 and HR expression and the relationships between the original treatments and the secondary chemotherapy for recurrence were evaluated. Results We obtained 27 samples from 36 recurrence patients. For metachronous recurrence metastases, the HER 2 status changed in 18.5% （5/27）. Three patients changed from positive to negative, while 2 patients converted from negative to positive. A change in ER status was observed in 7 cases (25.9%): 5 cases from positive to negative and 2 cases from negative to positive. PR status changed in 2 cases from positive to negative and in 0 case from negative to positive. There was no significant correlations between the changes of HER-2 and the initial radiochemotherapy, anti-HR therapy.However, it was involved in down regulation of HR expression(Fisher exact test=0.026）.In Kaplan Meier analysis, patients with changes of HER-2 or HR expression had a mildly poor response to chemotherapy and progress-free survival （33.4 vs. 38.6 months, Log-rank=1.96, P=0.16）, compared with the patients without changes. Conclusion HER-2 and HR status had been changed during breast cancer progression in the metachronous recurrence patients.So it is necessary to re evaluate those biomarkers should be neoplastic tissue from metastatic site, whenever possible,for the recurrence patients.