The Relationship Between CEF/TE Neo-adjuvant Chemotherapy, MAPK/PI3K Signal Pathway And Ki-67 In Breast Cancer

Objective:To investigate the relationship between CEF/TE neo-adjuvant chemotherapy (NAC) and MAPK/PI3K signal pathway, the mechanism of CEF and TE neo-adjuvant chemotherapy, and the diagnostic and therapeutic value of C-erbB-2, pMEK, pAKT and Ki-67.Methods:We prospectively selected 27 patients with breast cancer in stageⅡ～Ⅲduring 2008.10～2011.2 in the general surgery department of affiliated hospital of Zunyi medical college. After diagnosed by core needle biopsy, these patients were randomly treated with CEF (12 patients) or TE (15 patients) neo-adjuvant chemotherapy for 3～4 cycles, and modified radical mastectomy was carried out two weeks later. The expressions of C-erbB-2, pMEK, pAKT and Ki-67 of tumor tissues were detected by immunohistochemistry (IHC) before and after the neo-adjuvant chemotherapy. Statistical methods was utilized to analyze the relationship between the therapeutic effect of CEF/TE neo-adjuvant chemotherapy and the expressions of C-erbB-2, pMEK, pAKT, Ki-67, and the influences of CEF/TE neo-adjuvant chemotherapy to these molecules.Results:(1) Before NAC, the expression of C-erbB-2 in tumor tissues is positively correlated with the expression of pMEK, pAKT and Ki-67(P<0.05); pMEK and pAKT both are positively correlated with Ki-67(P<0.05). (2) 21 patients of the two groups got partial response(PR), the objective response rate(OR) is 77.78%(21/27); 12 patients of the TE group got PR, OR:80%(12/15); 9 patients of the CEF group were PR, OR:75%(9/12); 2 patients got stable of disease(SD) and 1 patients got progressive of disease(PD) in each group, and no patient got complete response(CR). (3) Before NAC, the expression of C-erbB-2, pMEK, pAKT and Ki-67 are negatively correlated with the therapeutic effect in CEF group(P<0.05); the expression of C-erbB-2, pMEK and Ki-67 are negatively correlated with the therapeutic effect in TE group(P<0.05); pAKT has a negative related trend with the therapeutic effect in TE group, but this has no statistical significance (P=0.088). (4) The changes of the expression of C-erbB-2 after NAC have no statistical significance in both CEF and TE groups(P>0.05); the expression of pMEK is significantly down regulated after NAC in CEF Group (P<0.05); the expression of pAKT is up-regulated after treated with CEF regimen, but this has no statistical significance (P=0.102). After treated with TE regimen, the expression of pMEK, pAKTå'ŒKi-67 are significantly down-regulated (P<0.05).Conclusion:(1) C-erbB-2 can activate pMEK (the key protein of MAPK pathway) and pAKT(the key protein of PI3K pathway), and enhance the proliferation of breast cancer cells. This may correlate with the genesis and progression of breast cancer. (2) CEF regimen cannot affect the expression of C-erbB-2, it can inhibit the proliferation of breast cancer cells by inhibiting the expression of pMEK, but patients express high level of pMEK have a poor therapeutic effect; (3) TE regimen cannot affect the expression of C-erbB-2, it can inhibit the proliferation of breast cancer cells by inhibiting both pMEK and pAKT, but patients express high level of pMEK and pAKT have a poor therapeutic effect; (4) The reason why high level expression of pMEK and pAKT leads to poor therapeutic effect may correlate with multiple drug resistance proteins that induced by MAPK and PI3K pathway.