[Effects of cell cycle regulatory genes on breast cancer neo-adjuvant chemotherapy by M-FISH].

Objective: The dysregulation of cell cycle could influence cell proliferation, differentiation and response to medicine. The purpose of this study is to explore the correlation between cell cycle regulatory genes and breast cancer neo-adjuvant chemotherapy (NAC) in patients with local advanced breast cancer, and thus to find some predictors of NAC to provide guidance for clinical treatment. Methods: Ninety five cases of local advanced breast cancer were collected, which were treated with NAC of TAC (Taxanes/Anthracycline/Cyclophosphamide) regimen. Multi-gene fluorescence in situ hybridization (M-FISH) was used to study the correlation between copy number variations of cell cycle regulatory genes (c-myc, Mdm2, CCND1, CHEK2, Rb1, p53, p16, p21) and clinical effect of NAC. Results: In the effective group, there were 18 cases of c-Myc amplification and 52 cases of no amplification. There were 11 cases of CCND1 amplification and 59 cases of no amplification; 12 cases of p53 deletion and 58 cases without deletion; 11 cases of p16 deletion and 59 cases without deletion. In the ineffective group, there were 12 cases of c-Myc amplification and 13 cases of no amplification; CCND1 amplification in 9 cases, no amplification in 16 cases; p53 deletion in 10 cases, no deletion in 15 cases; p16 deletion in 10 cases and no deletion in 15 cases. The copy number of the above four genes was statistically different between the two groups. C-Myc gene amplification (P=0.040), CCND1 gene amplification (P=0.033), p53 gene deletion (P=0.020) and p16 gene deletion (P=0.012) were significant correlation with poor effect of NAC. Among them, the effect of NAC in patients with two or more genes copy number variations of c-Myc, CCND1, p53, p16 were poorer than that in patients with one or not gene copy number variations (P=0.000). In addition, the copy number variations of CCND1 (P=0.049), c-Myc (P=0.049), and p16 (P=0.008) were correlated with neo-adjuvant chemotherapeutic effect respectively in Luminal breast cancer, Her-2 positive breast cancer, and triple-negative breast cancer. Conclusion: These results indicated that the copy number variations of c-Myc, CCND1, p53, and p16 in patients were significant correlation with poor effect of NAC.