| Background: Breast cancer is one of the most common malignant tumors in women.In recent years,the trend of gradual increase has become the most common malignant tumor in female population,which seriously affects women's health.The sensitivity of different breast cancer types to chemotherapeutic drugs and their prognosis are different.With the advancement of various therapeutic techniques such as surgery,chemotherapy,radiotherapy,and endocrine therapy,neoadjuvant chemotherapy(NAC)can improve the resection rate,breast-conservation rate,tumor stage,and tumor understanding of chemotherapy.Sensitivity has occupied an important position in breast cancer treatment research in recent years.At present,the neoadjuvant chemotherapy regimen is mostly based on postoperative adjuvant chemotherapy,and the international guidelines do not have a clear guidance.The anthracycline-based EC-TC regimen used in this study is a commonly used treatment program in the world.In China,due to concerns that the toxic side effects of anthracyclines are often not strictly followed by standard doses of neoadjuvant chemotherapy,they have been used in the past.The efficacy of neoadjuvant chemotherapy for anthracyclines did not meet expectations.This study was designed to investigate the efficacy and safety of neoadjuvant chemotherapy in patients with standard doses of doxorubicin versus low-dose epirubicin.In the context of precision medicine,effective monitoring of the efficacy of neoadjuvant chemotherapy is extremely important,and there is still a lack of effective predictive indicators of neoadjuvant chemotherapy in clinical practice,resulting in many patients receiving ineffective or unnecessary chemotherapy.At present,neoadjuvant chemotherapy is determined by pathological molecular typing,and whether the standard dose-related factors related to neoadjuvant chemotherapy can effectively predict the efficacy needs further verification.Next-generation sequencing(NGS)technology is widely used in whole-genome sequencing,whole-exome sequencing,gene regulation,and trans-transcriptional level research,and is applied in the field of tumor etiology,diagnosis and treatment.A breakthrough in progress.Previous studies have sequenced breast cancer-related genes by using NGS technology,and found that 10 common mutations such as TP53,PIK3 CA,and RB1 are associated with breast cancer chemotherapy.However,there are few studies on NGS technology in neoadjuvant chemotherapy for breast cancer patients.Therefore,it is necessary to further explore whether NGS technology can be used to detect sensitive indicators for predicting the efficacy of neoadjuvant chemotherapy for breast cancer.Objective: To investigate the efficacy and safety of standard doses of doxorubicin recommended by foreign guides in Chinese patients with stage II~III breast cancer,and the correlation between NGS,multi-parameter MRI,efficacy-related factors and efficacy.Methods: From May 2016 to April 2018,the first affiliated hospital of Anhui Medical University was enrolled in the Department of Breast Surgery and was diagnosed as stage II~III invasive breast cancer(except Luminal A)by hollow needle biopsy and clinical examination.The breast cancer patients who completed the surgery after chemotherapy were 65 patients in the standard dose of epirubicin,using EC-TC(epitamycin 100mg/m2 d1,cyclophosphamide 600 mg/m2 d1 every two weeks,A total of four courses of treatment,sequential paclitaxel 80 mg / m2 + carboplatin AUC = 1.5 d1 once a week for 12 weeks)program,the solid tumor efficacy evaluation standard RECIST1.1 as the standard to judge the clinical efficacy of the standard dose group.Another retrospective study of breast cancer patients who were diagnosed in the clinical and pathological features of the Anma Grandma Breast Surgery and the standard dose group from April 2015 to April 2016,65 patients in the low dose group of epirubicin,using FEC-T(Fluorouracil 500 mg/m2 d1,epirubicin 75 mg/m2d1,cyclophosphamide 600 mg/m2 d1 every three weeks for a total of four courses,sequential Paclitaxel 80 mg/m2d1 once a week A total of eight courses).The clinical efficacy of the low-dose group was judged by the pathological complete response rate(p CR).The curative effect of the two groups from neoadjuvant chemotherapy to preoperative chemotherapy was compared by p CR,and the standard dose table was evaluated according to the WH0 chemotherapy toxic side-reaction grading standard.The safety of themycin.The p CR rate and effective rate of the relevant factors in the standard dose group were compared to evaluate the correlation between each factor and the standard dose of neoadjuvant chemotherapy.The relationship between multi-parameter MRI and efficacy was judged by comparing the p CR rates of different TIC types of breast MRI in the standard dose group.The differences in p CR patients and Non-p CR patients were compared between 32 patients in the standard dose group by NGS high-throughput sequencing,and their correlation with the standard dose EPI neoadjuvant chemotherapy regimen was analyzed to explore with China.The next-generation sequencing(NGS)technique was used to detect the mutations and single-nucleotide polymorphisms(SNPs)of breast cancer-related genes in patients with p CR and Non-p CR,and to find sensitive predictors for evaluating efficacy.Results: total of 130 patients were enrolled,of which 65 patients were enrolled in the low-dose epirubicin group,with an average age of 45.67 years.The standard dose of doxorubicin was enrolled in 65 patients,with an average age of 47.37 years.The clinical features of the patients were balanced and there was no statistical difference(P>0.05).1.The standard dose table of patients with adriamycin group had a p CR rate of 16 cases(24.62%)and a low dose group of p CR rate of 3 cases(9.23%).The difference was statistically significant(P<0.05).2.Standard dose group age ? 50 years,clinical stage III,tumor size T2,lymph node N1 or N2,triple negative breast cancer,Ki-67% ? 14% of breast cancer patients have a higher p CR rate.Among them,the difference of p CR rate of Ki-67%?14% was 14(31.91%)and Ki-67%<14%(5.56%).The difference was statistically significant(P<0.05).There was no significant difference in the difference(P>0.05).3.TIC perfusion curve of multi-parameter MRI in standard dose group The p CR rate of patients with type III before chemotherapy was 11 cases(26.19%),the p CR rate of type III-II was 4 cases(23.53%),and the rate of type II p CR was 1 case.(16.67%).The p CR rate and effective rate of patients with TIC perfusion curve type III were higher than those of type III-II and type II,but the difference was not statistically significant(P>0.05).4.In the standard dose group,TP53 was the breast cancer-related gene with the highest mutation rate.The mutation rates of p CR group and Non-p CR group were(16.7%)and(30%),respectively.The difference of SETD2 rs4082155,XPCrs1870134,CYP2B6rs2279343 and ERBB2rs1058808 in SNPs with different p CR and Non-p CR patients was statistically significant(P<0.05).5.The standard dose group of grade II ~ IV WBC reduction,III ~ IV neutropenia,grade II ~ III liver function damage,abnormal ECG,cardiotoxicity were higher than the low dose group;low dose group of 0 ~I grade WBC reduction,grade 0~II neutropenia,grade 0~I liver function damage was higher than the standard dose group.However,the difference was not statistically significant(P>0.05).Conclusion:1.The p CR rate of Chinese standard stage II-III breast cancer patients using the standard dose of doxorubicin neoadjuvant chemotherapy has a significant advantage compared with the low dose epirubicin group.The standard dose group is more effective than the low dose.2.Chinese patients with breast cancer use the standard dose of doxorubicin,age ? 50 years,clinical stage is stage III,tumor size is T2,lymph node is N1 or N2,triple negative breast cancer,Ki-67% ? 14% Breast cancer patients have better efficacy,and the expression of Ki-67 is associated with efficacy.3.Chinese breast cancer patients with standard dose of doxorubicin neoadjuvant chemotherapy in multi-parametric MRI TIC typing in patients with perfusion curve type III have better efficacy.4.Mutations in the TP53 gene and SETD2rs4082155,XPCrs1870134,CYP2B6rs2279343,and ERBB2rs1058808 may be sensitive predictors of the efficacy of neoadjuvant chemotherapy for doxorubicin at standard doses.5.Chinese breast cancer patients were well tolerated with the standard dose of doxorubicin.The incidence and extent of adverse reactions were not significantly different from those of the low dose group. |
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