Clinical Study On The Intervention Of Huadu Sanyin Recipe On The Recurrence And Metastasis Of Triple-negative Breast Cancer And The Mechanism Of MiRNA

Objective:Breast cancer now ranks first among new cancers in the world,seriously endangering women's health.Triple-negative breast cancer accounts for 12%-17%of all breast cancers.There is no effective maintenance treatment after surgery,radiotherapy,and chemotherapy.It has the characteristics of high invasiveness,easy recurrence and metastasis within 1-3 years.Therefore,triple-negative breast cancer should be intervened within 1-3 years after the first treatment to prevent recurrence and metastasis,reduce its mortality,and improve long-term survival,which is of great significance.Due to the lack of molecular targets and corresponding treatment methods,it provides an entry point for traditional Chinese medicine to prevent the recurrence and metastasis of triple-negative breast cancer.The purposes of this study are to observe the clinical efficacy and safety of the Huadu Sanyin Fang in preventing and treating recurrence and metastasis of patients with triple-negative breast cancer,discuss the correlation between patients'general condition,tumor characteristics,different physical conditions,recurrence and metastasis,and explore the molecular mechanism in patients with triple-negative breast cancer.Methods:In this study,a single-arm research method was adopted,and patients with triple-negative breast cancer who had completed postoperative adjuvant treatment were included as the treatment group.The Huadu Sanyin Fang was used as the basic prescription to differentiate the symptoms and signs.The patients were followed up for 3 years to observe the 3-year disease-free survival rate,evaluate the quality of life and breast cancer changes in related symptoms(including sleep,fatigue,anxiety,and depression),and analysis of their general conditions,tumor characteristics,different physiques,and tumor recurrence and metastasis.We used Hiseq database-building sequencing technology to detect the differentially expressed miRNAs of patients with different physiques(physical constitutions related to tumor recurrence and metastasis).We used biological information technology to predict its key target genes and pathways.We collected peripheral blood of patients with different constitutions(physiques related to tumor recurrence and metastasis)to detect the changes in the expression levels of core genes in key pathways before and after taking the medicine.Results:1.A total of 141 patients with triple-negative breast cancer were enrolled in this study,aged between 30-70,with an average age of 49.04±9.763 years old.The physical distribution was dominated by qi deficiency,blood stasis,and qi stagnation,and the proportions were 18.44%and 13.48 respectively.%,15.60%.A total of 141 patients completed a 3-year follow-up of 135 cases,and 7 cases(4.96%)were lost to follow-up,including 4 cases of lymph node metastasis,6 cases of lung metastasis,4 cases of liver metastasis,2 cases of bone metastasis,and 2 cases of breast recurrence in situ.2.According to Kaplan-Meier survival analysis,the shortest disease-free survival period was 6.7 months,the longest disease-free survival period was 36 months,the average follow-up time was 33.70±0.55 months,and the 3-year disease-free survival rate was 87%.Compared with before treatment,TCM symptoms,PSQI,RPFS,and HADS scores of the patients decreased after treatment,and the total score of FACT-B increased,and the difference was statistically significant(P<0.05).Compared with before treatment,the scores of physiological status,social and family status,emotional status,functional status,and additional attention in FACT-B all increased,and the difference was statistically significant(P<0.05).3.According to Kaplan-Meier survival analysis,the survival curve of Qi-deficiency patients was lower than that of non-qi-deficiency patients,and the decline was steeper,which indicated that the prognosis of Qi-deficiency patients is worse than that of non-qi-deficiency patients.Kaplan-Meier survival analysis showed that tumor diameter and lymph node metastasis are related to the recurrence and metastasis of triple-negative breast cancer.COX regression analysis showed that tumor size is an independent prognostic factor for patients with triple-negative breast cancer.4.There are a total of 49 miRNAs differentially expressed between Qi deficiency and peaceful constitution,16 up-regulated,33 down-regulated,and the top 20 miRNAs with the largest difference were predicted to have a total of 7088 target genes that could be regulated.We further compared them with three-negative breast cancer target genes.There were 1445 genes in the intersection.The PPI and KEGG pathway enrichment analysis showed that the key genes are mainly TP53,AKT1,EGFR,MAPK3,VEGRA,TNF,etc.,and the key pathways are PI3K/AKT,MAPK,RAS signaling pathways,etc.5.Compared with before taking the medicine,the expression of NFKB1,AKT1,PIK3CA on PI3K/AKT signaling pathway in patients with triple-negative breast cancer and Qi deficiency was down-regulated,and the expression of Bcl-xL was up-regulated.The difference of NFKB1 and AKT1 expression before and after treatment was statistically significant.Conclusion:1.Under the guidance of "Disease Differentiation-Syndrome Differentiation" Diagnosis and Treatment,the Huadu Sanyin Fang can improve the 3-year disease-free survival rate of patients with triple-negative breast cancer,and can significantly improve fatigue,physical strength,sleep problems,anxiety,and depression for triple-negative breast cancer patients in better safe way.2.In the analysis of influencing factors for the recurrence and metastasis of triple-negative breast cancer,lymph node metastasis,tumor size,physical status are related to tumor recurrence and metastasis,and other factors are not related.In COX regression multivariate analysis,tumor size is an independent prognostic factor for the recurrence and metastasis of triple-negative breast cancer.3.There are 49 types of miRNAs differentially expressed in triple-negative breast cancer patients with Qi-deficiency quality and moderate quality.The main target genes involved are TP53,AKT1,etc.,and the key pathways include PI3K/AKT signaling pathways.4.The effect of the Huadu Sanyin Fang in preventing the recurrence and metastasis of triple-negative breast cancer may be achieved by regulating the gene expression levels on the PI3K/AKT/NF-KB pathway.Compared with before taking the medicine,the expression of NFKB1,AKT1,PIK3CA in the PI3K/AKT signaling pathway of triple-negative breast cancer patients are down-regulated,and the expression of Bcl-xL is up-regulated.The difference between NFKB1 and AKT1 is statistically significant.