| Objective:Morbidity of Breast cancer has been increasing year by year. It severely threatens women’s health. In 2013, according to Chinese Anti-cancer Association, there were about 210,000 patients suffering breast cancer firstly and about 50,000 died. The death of breast-cancer patients’ are mainly caused by the distant metastases of advanced breast cancer. Thus, the control of distant metastases is the main method to improve the long-term survival of breast-cancer patients. As the standard therapy of Locally advanced breast cancer(LABC), Neoadjuvant chemotherapy(NAC) can remove the micro metastases all over the body, shrink tumors, and improve the rate of breast conservation, and the survival rate of patients who acquire pathology complete release(p CR) after chemotherapy can be increased, widely used in clinical treatment.With the development of molecular biology, many molecular biology indexes have been or are being used in the clinical treatment, prognosis and the prediction of chemotherapy curative effect. The biological factors of current clinical routine inspection are ER, PR, P53, HER-2 and Ki-67. Researches reveal that Ki-67 as the proliferation index will reflect the state of tumor cell proliferation and it is the important index to detect the curative effect in NAC. Ki-67, also called cell proliferation antigen, is a nuclear protein with nuclear function concerned with caryocinesis and an antigen directly reflecting the proliferative activity of tumor cells. It can indicate the proliferation rate of tumor cells and is closely related to the occurrence, infiltration and metastases process. So, it has been treated as the key biological index for prognosis and the decision of systematical therapy in clinical treatment.As is known to all, the clinical effects will be different even when the patients with the same clinical stage and pathological type adopt the same chemotherapy program. The good NAC evaluation method can be favorable for both the immediate adjustment of chemotherapy program and the postoperative adjuvant chemotherapy. There is no doubt that the changes of tumor imaging can be one of the standards to evaluate the effects of NAC, but there also exists limits because the retraction ways of tumors are not the same centripetal retraction. Thus, it is important to find a simply, objectively, and effectively scientific evaluation method to predict the effects of NAC for breast cancer. But can the changes of Ki-67 reflect the chemotherapeutic effect? What the change rules? How to adjust the therapy program according to the changes of the indexes? The objective of this research is to use Ki-67 as the evaluation indexes to observe the changes of the indexes before and after NAC, compare changes of patients’ clinical and biological indexes of breast-caner and tumor imaging, explore the clinical significance of the changes of Ki-67 before and after NAC in order to provide evidence for the evaluation of NAC effects, the formulation of reasonable follow-up treatment and the improvement of whole effects of LABC.Methods : The date of 191 breast-cancer patients who have firstly received NAC during stage IIb-IIIc were collected from Hebei Breast Disease Diagnosis and Treatment Center and Hebei Civil Hospital from January of 2007 to January of 2010.All of them are female, aged from 29 to 71, with the middle age of 48. They all have been confirmed suffering breast-cancer checked by core needle biopsy before chemotherapy and have been verified that there is no distant metastases. The expressions of ER, PR, Ki-67, and HER-2 of patients before chemotherapy have been examined by immunohistochemical method. The program with anthracyclines was used through 4-6 cycles: cyclophosphamide 500mg/m2, d1; pharmorubicin 100mg/m2 or pirarubicin 60mg/m2, d1, every three weeks as a cycle; or combination of anthracene nucleus and taxane: TE or TEC program: pharmorubicin 75mg/m2, d1, taxol 175mg/m2 or docetaxel 75mg/m2, d2, TEC program with cyclophosphamide 500mg/m2, d1; every three weeks as a cycle; the clinical effect was evaluated 18 days later after chemotherapy during every 2 cycles. All the cases have received standard chemotherapy for 4-6 cycles and then received operations. The specimen has received the postoperative routine pathological detection and immunohistochemical method has been used to check the expression of the same biological factors, and the relationship between expression status of biological factors and clinical effect has been analyzed. According to St. Gallen experts of 2013, all the cases are divided into four subtypes groups: Luminal A, Luminal B, Triple negative, and HER2 overexpression type. The rate of p CR(pathology complete release) of every subtype patient has been analyzed. All the patients have been received the routine follow-up visits after operations. And the RFS(Relapse Free Survival) was analyzed based on the expression of Ki-67 and molecular classification.Results:1 Follow-up visits: the period of follow-up visits is about 24 months to 84 months, and the median follow-up visits is about 56 months; the follow-up visits of 185 cases have been finished and 6 lost, with the rate of 96.8%; 46 of them recurred, 11 died and 128 survived.2 The relationship between changes of Ki-67 and prognosis: among 185 cases, the Ki-67 of 31 patients increased, 133 of them decreased, with 21 unchanged. The expression of Ki-67 after chemotherapy is below the level before chemotherapy.RFS of the decreased group is higher than that of the un-decreased group. There is statistical significance of the difference between the two groups(2c=9.409,P =0.002).3 The relationship between changes of Ki-67 and molecular subtyping: the Ki-67 of 58.0%Luminal A, 85.7%Luminal B,73.1% Triple negative and 76.4% HER2 overexpression type decreased after NAC; Ki-67 expression of Luminal B, Triple negative and HER2 overexpression type decreased, which has the statistical significance(P <0.01).4 The relationship between Ki-67 changes of breast cancer molecular subtypes and prognosis: for Luminal A, there is no difference between RFS of Ki-67 decreased group and that of the un-decreased group and no statistical significance(2c=0.649,P =0.420). For Luminal B, RFS of Ki-67 decreased group is higher than that of the un-decreased group, and the difference has statistical meaning(2c=7.598,P=0.006). For Triple negative ones, RPS of Ki-67 decreased group is higher than that of the un-decreased group, and the difference has statistical meaning(2c=4.546, P=0.033). For HER2 overexpression types, RPS of Ki-67 decreased group is higher than that of the un-decreased group, and the difference has statistical meaning(2c=3.973,P =0.046).Conclusion:1 The RFS of Ki-67 decreased group after chemotherapy was better than that of un-decreased group, which means that the decrease of Ki-67 after chemotherapy predicts the good clinical effects and good prognosis.2 In molecular subtypes of breast cancer, the reaction of Luminal A to chemotherapy is low with unobvious decreased Ki-67; but the expression of Ki-67 of Luminal B, Triple negative and HER-2 overexpression type decreased obviously, and their rate of p CR is higher than that of Luminal A, which means that the decrease of Ki-67 is related to the effect of chemotherapy.3 In subgroup analysis, the change of Ki-67 of Luminal A before and after chemotherapy is not related with RFS. But the decrease of Ki-67 of Luminal B, Triple negative and HER-2 overexpression type is related to higher RFS, which means: the change of Ki-67 before and after chemotherapy is an independent prognostic factor for Ki-67 of Luminal B, Triple negative and HER-2 overexpression type. |
PDF Full Text Request