title: Evaluating the response of neoadjuvant chemotherapy for treatment of breast cancer: are tumor biomarkers and dynamic contrast enhanced MR images useful predictive tools?
abstract: 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.
authors: 1 Department of Breast Surgery, 2 Department of Pathology, 3 Department of Radiology, Huashan Hospital, Fudan University, Shanghai 200052, China.
authors: Zijing
authors: Z
authors: Zhang
authors: 1 Department of Breast Surgery, 2 Department of Pathology, 3 Department of Radiology, Huashan Hospital, Fudan University, Shanghai 200052, China.
authors: Wei
authors: W
authors: Zhang
authors: 1 Department of Breast Surgery, 2 Department of Pathology, 3 Department of Radiology, Huashan Hospital, Fudan University, Shanghai 200052, China.
authors: Yiting
authors: Y
authors: Jin
authors: 1 Department of Breast Surgery, 2 Department of Pathology, 3 Department of Radiology, Huashan Hospital, Fudan University, Shanghai 200052, China.
authors: Hongying
authors: H
authors: Wang
authors: 1 Department of Breast Surgery, 2 Department of Pathology, 3 Department of Radiology, Huashan Hospital, Fudan University, Shanghai 200052, China.
authors: Fei
authors: F
authors: Gu
authors: 1 Department of Breast Surgery, 2 Department of Pathology, 3 Department of Radiology, Huashan Hospital, Fudan University, Shanghai 200052, China.
authors: Jian
authors: J
authors: Zhou
authors: 1 Department of Breast Surgery, 2 Department of Pathology, 3 Department of Radiology, Huashan Hospital, Fudan University, Shanghai 200052, China.
authors: Zhengyin
authors: Z
authors: Lao
authors: 1 Department of Breast Surgery, 2 Department of Pathology, 3 Department of Radiology, Huashan Hospital, Fudan University, Shanghai 200052, China.
authors: Zude
authors: Z
authors: Xu
authors: 1 Department of Breast Surgery, 2 Department of Pathology, 3 Department of Radiology, Huashan Hospital, Fudan University, Shanghai 200052, China.
authors: Feng
authors: F
authors: Tang
authors: 1 Department of Breast Surgery, 2 Department of Pathology, 3 Department of Radiology, Huashan Hospital, Fudan University, Shanghai 200052, China.
authors: Liping
authors: L
authors: Zou
authors: 1 Department of Breast Surgery, 2 Department of Pathology, 3 Department of Radiology, Huashan Hospital, Fudan University, Shanghai 200052, China.
authors: Weijun
authors: W
authors: Tang
authors: 1 Department of Breast Surgery, 2 Department of Pathology, 3 Department of Radiology, Huashan Hospital, Fudan University, Shanghai 200052, China.
authors: Rong
authors: R
authors: Lu
authors: 1 Department of Breast Surgery, 2 Department of Pathology, 3 Department of Radiology, Huashan Hospital, Fudan University, Shanghai 200052, China.
authors: Qiang
authors: Q
authors: Zou
keywords: Breast cancer; Ki-67; P-glycoprotein (P-gp); neoadjuvant chemotherapy (NAC); pathological complete response (pCR)