The Study Of Correlation Between QM-FISH Results Of Cell Cycle Regulatory Genes And Breast Cancer Neoadjuvant Chemotherapeutic Effect

Objective: To research and analyze the correlation between copy number variation of G1/S checkpoint regulatory genes and clinical effect of neoadjuvant chemotherapy in patients with local advanced breast cancer,in order to find some predictors of neoadjuvant chemotherapy to provide guidance for clinical treatment.Methods: 1.This research selected 95 cases of local advanced breast cancer from March 2012 to March 2014 which were treated with neoadjuvant chemotherapy in Tianjin Medical University Cancer Hospital. All of the patients were preliminary diagnosed as primary invasive breast cancer through coarse needle aspiration biopsy before the surgery. They were all treated with neoadjuvant chemotherapy of TAC(Taxanes/Anthracycline/Cyclophosphamide) regimen for 6 cycles.2.The collection of the breast tumor tissue from coarse needle aspiration biopsy were fixed with 10% Formaldehyde, dehydrated and then embedded in paraffin. Paraffin sections were sliced at a 4μm thickness. Quantitiative multi-gene fluorescence in situ hybridization(QM-FISH) was used in paraffin sections to study copy number variation of G1/S checkpoint regulatory genes(c-Myc、Mdm2、CCND1、CHEK2、Rb1、p53、p16、p21).3.The SPSS 19.0 statistical software was applied to statistical analysis. The correlation between copy number variation of G1/S checkpoint regulatory genes and clinical effect of neoadjuvant chemotherapy were analyzed through two independent samples χ2 test and multiple independent samples rank sum test(Kruskal-Wallis test for independent samples). P<0.05 was considered as statistical significance.Results: 1.Effective group patients had smaller tumors(P=0.018), the proportion of ER-negative patients(P=0.032) and Ki-67 high expression patients(P=0.030) were higher than the ineffective group.2. The proportion of patients who simultaneously accompanied multiple gene copy number variations in invalid group is higher than effective group(P=0.000).The frequency of G1/S checkpoint regulatory gene copy number variations were significant correlation with effect of neoadjuvant chemotherapy in breast cancer patients of Luminal A(P=0.011) and Luminal B(P=0.034).3.The CNVs of c-Myc(P=0.040), CCND1(P=0.033), p53(P=0.020) and p16(P=0.012) were significant correlation with poor effect of neoadjuvant chemotherapy.The patients with two or more genes copy number variations had poorer effect of neoadjuvant chemotherapy than the patients with one or not gene copy number variations.The frequency of these four genes copy number variations were significant correlation with effect of neoadjuvant chemotherapy in breast cancer patients of Luminal A(P=0.028),Luminal B(P=0.025) and Her-2 positive(P=0.024).4. The CNVs of CCND1(P=0.049) were significant correlation with poor effect of neoadjuvant chemotherapy in Luminal breast cancer, the CNVs of c-Myc(P=0.049) were significant correlation with poor effect in Her-2 positive breast cancer, the CNVs of p16(P=0.008) were significant correlation with poor effect in triple-negative breast cancer.Conclusion: 1.The patients with small tumor size(≤T2), ER-negative, Ki-67 high expression(≥14%) and the molecular type of Her-2 overexpression and triple-negative breast cancer could achieve better efficacy.2.The CNVs of c-Myc, CCND1, p53 and p16 means poor efficacy of TAC neoadjuvant chemotherapy. The patients with two or more genes copy number variations had poorer effect of neoadjuvant chemotherapy.3.The CNVs of CCND1, c-Myc, p16 respectively correlated with neoadjuvant chemotherapeutic effect in patients of Luminal breast cancer, Her-2 positive breast cancer, triple-negative breast cancer.