The Relationship Between The Expression Of P-gp, MRP1 And BCRP And Response To TEC Neoadjuvant Chemotherapy And Molecular Typing In Breast Cancer

Objective: 1.Through the observation of the expressions and their expression changes of P-gp?MRP1 and BCRP in breast cancer before and after neoadjuvant chemotherapy with TEC regimen and analyses of their relationships with the response to neoadjuvant chemotherapy,to evaluate their possible value as references to predict the outcome of neoadjuvant chemotherapy for breast cancer.2.To investigate whether the expression levels of P-gp,MRP1 and BCRP are relevant to the expressions of ER,PR,Her-2 and Ki-67 in breast cancer before the neoadjuvant chemotherapy,molecular subtyping and postoperative lymph node metastasis.Methods: Ninty eight patients with locally advanced breast cancer who were hospitalized in the Second General Surgery Department of the Affiliated Ganzhou Hospital of Nanchang University from January 2012 to December 2015 were included in this study.All the patients underwent ultrasound-guided Bard needle biopsy and all were diagnosed with invasive ductal carcinoma.All the patients received 4 to 6 courses of neoadjuvant chemotherapy with TEC regimen and subsequently underwent modified radical mastectomy.Evaluation of the size of primary lesion was performed both before the puncture biopsy and before the mastectomy by using the ultrasonography.Paraffin sections of original biopsy specimens and postoperative residual tumor foci were made and expressions of ER,PR,Her-2,Ki-67,P-gp,MRP1 and BCRP were investigated by immunohistochemistry.When the ICH of Her-2 is 2+,FISH test was further performed.The expressions of P-gp,MRP1 and BCRP before and after neoadjuvant chemotherapy were analyzed and possible correlations between their expressions before the neoadjuvant chemotherapy were investigated.Based on postoperative pathological findings,chemotherapy response was divided into grades I-III and the patients were divided into 3 groups accordingly.Expressions of P-gp,MRP1 and BCRP before neoadjuvant chemotherapy were compared between the groups to determine whether there were differences.Also,expressions of P-gp,MRP1 and BCRP their expression changes before and after neoadjuvant chemotherapy in groups of chemotherapy response grades I and?were compared,to determine the influence of P-gp,MRP1 and BCRP on the therapeutic effect of the neoadjuvant chemotherapy;In the meantime,patients were molecularly subtyped according to expressions of ER,PR,Her-2 and Ki-67 before the neoadjuvant chemotherapy.Possible correlations of P-gp,MRP1 and BCRP expressions with ER,PR,Her-2 and Ki-67 expressions,and with postoperative lymph node metastasis were analyzed.Results: A total of 98 patients were enrolled in the study.There was poor coherence between ultrasonographic findings and neoadjuvant chemotherapy response based on postoperative pathological results(Kappa coefficient is 0.426).Expression of MRP1 was related to the outcome of neoadjuvant chemotherapy with TEC regimen.MRP1 expressions before chemotherapy were significantly different among three chemotherapy response groups(P=0.016);Also,MRP1 expression in the group of chemotherapy response grade I was significantly higher than that of the group of chemotherapy response grade ?(P=0.006);MRP1 expression after chemotherapy in the group of chemotherapy response grade I was significantly higher than that of the group of chemotherapy response grade ?(P=0.023);MRP1 expression change before and after neoadjuvant chemotherapy in the group of chemotherapy response grade I was statistically higher than that in the group of chemotherapy response grade?grade group(P=0.019).There were no statistical differences in P-gp and BCRP expressions among the three chemotherapy response groups before and after neoadjuvant chemotherapy.We therefore speculate that the expressions of P-gp and BCRP were not related to the outcome of neoadjuvant chemotherapy with TEC regimen.The expression of MRP1 before neoadjuvant chemotherapy was correlated with ER expression and breast cancer molecular subtyping(P<0.05),but it was not correlated with expressions of PR,Her-2,and Ki-67,and axillary lymph node metastasis.The expressions of P-gp and BCRP before neoadjuvant chemotherapy were not correlated with expressions of ER,PR,Her-2,and Ki-67,breast cancer molecular subtyping,and axillary lymph node metastasis.Conclucions: The expression of MRP1,which is one of the ATP-binding cassette transporters,was related to TEC regimen neoadjuvant chemotherapy response in breast cancer.MRP1 expression before neoadjuvant chemotherapy was correlated with molecular biological marker of ER and breast cancer molecular subtyping.Although we didn't find correlations of P-gp,MRP1 and BCRP expressions with breast cancer proliferation marker Ki-67 and axillary lymph node metastasis,we think MRP1 could still be a predicting factor for breast cancer neoadjuvant chemotherapy response with TEC regimen.Combined with breast cancer molecular biological marker and molecular subtyping,the predicting value of MRP1 could even be higher.