评估新辅助化疗治疗乳腺癌的反应：肿瘤标志物和动态对比增强磁共振成像是否是有用的预测工具？
Evaluating the response of neoadjuvant chemotherapy for treatment of breast cancer: are tumor biomarkers and dynamic contrast enhanced MR images useful predictive tools?
机构信息
1 Department of Breast Surgery, 2 Department of Pathology, 3 Department of Radiology, Huashan Hospital, Fudan University, Shanghai 200052, China.
出版信息
J Thorac Dis. 2014 Jun;6(6):785-94. doi: 10.3978/j.issn.2072-1439.2014.04.28.
OBJECTIVE
In order to evaluate the therapeutic response to neoadjuvant chemotherapy (NAC) for breast cancer, this research focused on the changes in expression of tumor biomarkers and the correlations associated with changes of magnetic resonance imaging (MRI) pre- and post-NAC. We also compared the accuracy of MRI and pathology in terms of residual tumor extent after NAC.
METHODS
MRI was performed before and after four courses of cyclophosphamide, epirubicin and paclitaxel (CET) NAC on 114 patients treated in Huashan Hospital (Fudan University) from December 2009 to January 2013. All patients were pathologically diagnosed with invasive breast cancer via core needle biopsy. A series of tumor biomarkers, including P-glycoprotein (P-gp) and Ki-67, was tested by immunohistochemistry in both core needle biopsy and surgical specimens. The changes in tumor biomarker expression and the shrinkage of tumor on MRI were observed. The residual tumor extent after NAC was compared in terms of MRI and histopathology, and the accuracy of MRI was evaluated by both residual tumor extent and by NAC therapeutic effect. Together, these methods enabled a prognostic estimate of NAC.
RESULTS
The P-gp expression before NAC was used to evaluate the therapeutic effect of NAC. The up-regulation of P-gp expression after NAC was associated with poor therapeutic effect (P=0.0011). The expression of Ki-67 was significantly down-regulated (P<0.0001) but it had no association with NAC response (P=0.9645). The mean extent of residual tumor after NAC as seen on MRI was 20.83 mm (±4.14 mm, 95% CI) and that of surgically removed specimens, 18.89 mm (±3.71 mm, 95% CI). The sensitivity of MRI was 95.1%, the specificity was 28.6%, the positive predictive value was 79.6%, and the negative predictive value was 66.7%.
CONCLUSIONS
P-gp status was an important factor affecting the pathological complete response (pCR) rate. The change in P-gp expression, from negative to positive following NAC treatment, indicated the emergence of drug resistance resulting from chemotherapy. The down-regulation of Ki-67 was associated with the decline of tumor proliferation. However, compared to the pre-NAC P-gp status, the pre-NAC Ki-67 status had little prognostic value. Additionally, the evaluation of the efficacy of NAC by either MRI or histopathology was inconclusive.
目的
为了评估乳腺癌新辅助化疗（NAC）的治疗反应，本研究重点关注肿瘤标志物表达的变化，以及这些变化与 NAC 前后磁共振成像（MRI）的相关性。我们还比较了 MRI 和病理检查在 NAC 后残留肿瘤程度方面的准确性。
方法
2009 年 12 月至 2013 年 1 月，在复旦大学华山医院接受环磷酰胺、表阿霉素和紫杉醇（CET）NAC 四个疗程治疗的 114 例患者进行了 MRI 检查。所有患者均经核心针活检病理诊断为浸润性乳腺癌。通过免疫组织化学方法检测核心针活检和手术标本中一系列肿瘤标志物，包括 P-糖蛋白（P-gp）和 Ki-67。观察肿瘤标志物表达的变化和 MRI 上肿瘤的缩小情况。比较 NAC 前后 MRI 和组织病理学的残留肿瘤程度，并通过残留肿瘤程度和 NAC 治疗效果评估 MRI 的准确性。这些方法共同对 NAC 进行了预后估计。
结果
NAC 前 P-gp 表达用于评估 NAC 的治疗效果。NAC 后 P-gp 表达上调与治疗效果差相关（P=0.0011）。Ki-67 的表达显著下调（P<0.0001），但与 NAC 反应无关（P=0.9645）。MRI 上观察到的 NAC 后残留肿瘤的平均程度为 20.83mm（±4.14mm，95%CI），手术切除标本为 18.89mm（±3.71mm，95%CI）。MRI 的灵敏度为 95.1%，特异性为 28.6%，阳性预测值为 79.6%，阴性预测值为 66.7%。
结论
P-gp 状态是影响病理完全缓解（pCR）率的重要因素。NAC 治疗后 P-gp 表达由阴性转为阳性，表明化疗产生了耐药性。Ki-67 的下调与肿瘤增殖的下降有关。然而，与 NAC 前 P-gp 状态相比，NAC 前 Ki-67 状态的预后价值较小。此外，MRI 或组织病理学评估 NAC 的疗效并不一致。
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