The Study Of PARP-1、BRCA-1Protein In Prediction Of Neoadjuvant Chemotherapy Effectiveness And Their Prognostic Values

Objectives:Breast cancer is a highly heterogeneous tumor at the molecular level and the response to chemotherapy between breast cancer patients is large differences. The aim of this study was to investigate the efficacy of NAC for breast cancer on poly ADP-ribose polymerasel (PARP-1) and BRCA1, and to explore the value of PARP-1and BRCA1predict response of NAC in breast cancer, and further to investigate of their relationship with patient’s prognosis in breast cancer.Methods:105Female patients with breast cancer were selected from the department of breast in Cancer Institute and Hospital of Tianjin Medical University, from2007June to2009September. Expression of Ki67and ALDH1before and after NAC were measured by immunohistochemisthy(IHC).Their clinical and pathological features and prognosis were retrospectively analyzed.Results:1.105female patients were treated2-4cycles NAC. The complete response (CR) rate was18.1%(19/105), the partial response56.2%(59/105),the stable disease (SD) rate was24.8%(26/105), and the progress disease (PD) was0.9%(1/105).The clinical response rate was (cCR+cPR)74.3%.The result of pathology assessment:high sensitivity in18cases (17.1%), moderately sensitive in28cases(26.7%), light sensitive in30cases(28.6%), no sensitive in29cases(27.6%). The overall pathological response was72.4%.2. In total, positive expressed PARP-1were49.5%(52/105)tumors before chemotherapy, whereas81.0%(85/105) after chemotherapy. The positive expression of PARP-1after NAC was significant higher than that before NAC (P<0.05). BRCA1positive expression rate was48.6%(51/105) before chemotherapy and69.5%(73/105) after chemotherapy. The positive expression of ALDH1before NAC was significant lower than that after NAC (P<0.05).3. The response to NAC in PARP-1positive expression group was significantly higher than that in negative group(56.6%VS43.4%, P=0.019). The response to NAC in BRCA1positive expression group was significantly higher than that in negative group (P=0.026).4.The DFS of PARP-1protein positive group is lower than PARP-1protein negative group, the difference was statistically significant (P=0.004). The OS of PARP-1protein positive group is lower than PARP-1protein negative group, the difference was statistically significant (P=0.043).Multivariate Cox regression analysis showed that PARP-1was prognostic factor in breast cancer. 5. The DFS of BRCA1protein negative group is lower than PARP-1protein positive group, the difference was statistically significant (P=0.038). The OS of BRCA1protein negative group is lower than BRCA1protein positive group, but this did not reach statistic significance (P=0.822).Multivariate Cox regression analysis showed thatBRCAl had a independent prognostic value for DFS.Conclusions:1. Chemotherapy can change the expression of PARP-1and BRCA1in breast tumor. Chemotherapy can increase the expression of PARP-1and BRCA1.The expression of PARP-1and BRCA1predicts high sensitivity to neoadjuvant chemotherapy, so we can monitor response to threatment by detecting PARP-1and BRCA1.PARP-1and BRCA1can be marker for predicting the effect of NAC.2. In breast cancer,PARP-1protein expression had the worse prognosis. As a potential target for PARP inhibitors, PARP-positive breast cancer might become a new, clinically relevant entity.3. BRCA1expression may play an important role in the pathogenesis and prognosis of breast cancer, who may be candidates for trials investigating new therapies in combination with standard adjuvant therapy.