Association Of Ki67 With Clinicopatholoical Characteristics And Efficacy Of Neoadjuvant Chemotherapy In Breast Cancer

Background and Purpose:So far many researches have confirmed that neoadjuvant chemotherapy (NCT) on breast cancer is one of the standard treatments on locally advanced breast cancer. Recently, Ki67 is the common label in judging proliferation activity in tumor cells. Its high expression is the indicator of poor prognosis of breast cancer. But there is no agreed conclusion about whether Ki67 can be used as the forecasting indicator in NCT.The article aims at analyzing the connection among different Ki67 proliferation levels and the effects of NCT, ages,sizes of breast tumor, transfer of lymph node,estrogen receptor (ER), progesterone receptor (PR),and the expression of HER-2 and prognosis in breast cancer patients.The article also intends to explore the significance of Ki67 in breast cancer patients and the clinical pathological characteristics in forecasting the effects of NCT and the evaluation of prognosis.Research Methods:The article has retrospective analysis of the clinical data on 320 cases of breast cancer patients from 2009.1 to 2014.1.It owns pathologic diagnosis and the results of molecular marker (Ki67,ER,PR,HER-2).staging criteria of theseventh version on AJCC.And the clinical stage is Ⅱ-Ⅲ,315 of the patients were invasive ductal carcinoma.5 patients were invasive lobular carcinoma.All the patients received NCT for four to six cycles.280 cases applied TA plan: epirubicin Plus paclitaxel.12 cases applied TP plan:paclitaxel plus carboplatin.2 8 cases applied TCH plan:paclitaxel plus carboplatin Plus trastuzumab.With in one month’s treatment of NCT.the patients received operation on breast cancer, and according to the postoperative pathological report,doctors ensured the curative effects of chemotherapy,the adjuvant chemotherapy after operation.We did follow up (telephone follow-up,the hospital review) on all the patients.The deadline was May 2014,or the lost date and the death date. Based on the expression of Ki67 in pathological report before chemotherapy, we regarded value index of Ki67≤14% as low expression,Ki67>14% as high expression. Then by means of the software SPSS 19.0 we did statistical analysis on the clinical parameter in ages, breast mass diameter, the status of axillary lymph nodes, ER, PR, HER-2, curative effects, DFS, OS etc. At last,the relevance and difference between various expressions of Ki67 and each clinical indicator were achieved.Results:1、The expression of Ki67 had negative correlation with ER,PR,and positive correlation with HER-2 and breast tumor diameter,P<0.05.There was no obvious correlation among the expression of Ki67 and ages,menstruation, axillary lymph node status,P>0.05.2、Before receiving NCT, the pCR rate of Ki67 in high expression was betterthan that in low expression (18.0%vs8.6%,P=0.033).After chemotherapy, the expression of Ki67 in falling group was better than that in no descending group (19.8%vs 1.3%,P=0.000)3、the best cut-off value of ki67 was 35%,the area of ki67 under the ROC curve was 0.673,P=0.0001.4、Using Kaplan-Meier Method to analysis survivate, it was found that before receiving NCT,DFS and OS of Ki67 in low expression group were better than that in high expression group,P=0.034 in both groups. The prognosis of Ki67 high expression group pCR patients was similar to that of the Ki67 low expression group, but the prognosis of Ki67 high expression group not pCR patients was far worse than that of Ki67 low expression group.But after the chemotherapy, there was no remarkable correlation among the decreasing or increasing degree of Ki67 with prognosis.5、Luminal A subtype, Luminal B subtype, HER-2 over expression subtype and the value of mean of Ki67 in three negative breast cancer were 7.48%　36.11%　21.31% 42.56 respectively, the three negative subtype was obviously higher than the other three subtypes, P=0.000, a statistically significant difference.Considering the curative effects of NCT, Luminal A subtype<Luminal B subtype< three negative subtype<HER-2 over expression subtype,the pCR rates were 1.4%%　15.3%% 22.0%、31.1%　respectively, and the sensibility of three negative subtype to chemotherapy was much higher than those three subtypes. Using Kaplan-Meier Method to do survival analysis, it was found that in three years,LuminalA subtype (97.3%)>Luminal B subtype (91.7%)>three negative subtype (85.7%) >HER-2 over expression subtype (84.7%),P=0.08.The effects of short term chemotherapy was poor but better in long term survival.6、By making single factor analysis, the pCR rate in ER, PR negative group was remarkably higher than that in positive group,26.9% vs 7.4%, P=0.000,22.7% vs 10.9%,P=0.005, respectively. There was no obvious difference among pCR and HER-2 negative, or over expression (or amplification), P=0.174.7、According to the different ages, I divided the 320 patients into the young group, the middle-aged group and the older-age group, the value of mean of Ki67 in three groups were 33.48,27.63,23.74 respectively. And the young group was much higher than the other groups, P=0.048.8、The research included seven factors, which influenced COX single factor analysis in breast cancer DFS P<0.2:It put all these seven factors into multiple anaysis,the variation trend of Ki67 after chemotherapy (increasing or decreasing) was the independent prognostic to DFS,P=0.000. The research included seven factors, which influenced COX single factor analysis inbreast cancer OS P<0.2:It put all these seven factors into multiple anaysis,achieved three independent prognostic factors:expression Ki67 before c-hemotherapy, P=0.048, the variation trend of Ki67 after chemotherapy (increasing or decreasing),P=0.000,and the breast tumor diameter, P=0.009.Conclusion:The patients who showed high expression to Ki67 were more sensitive to chemotherapy, got a higher rate of pCR, but had a worse long term survival than that in low expression group. The prognosis of Ki67 high expression group pCR patients was similar to that of the Ki67 low expression group. Ki67 forecast pCR cut-off value was 35%. According to multiple regression analysis of elements, the expression of Ki67 before NCT, the variation tendency of Ki67 after chemotherapy and the sizes of breast masses were the independent prognostic factors influencing OS. After chemotherapy, the variation tendency of Ki67 was the independent prognostic factor influencing DFS. ER,PR, Ki67 and molecular typing could be used as the forecasting index of NCT curative effect. Among all the molecular typing, the curative effect of Chemotherapy of Luminal A subtype was worse than other molecular typing, but it enjoyed the longest term survival. Three negative breast cancer Ki67 had the highest value of mean,was the most sensitive to chemotherapy, but the prognosis was poor.