| BackgroundAs the economic development,the dietary structure changes,the environment changes,the living pressure is increased,so that many women have high fat,high protein eating structure changes,late marriage and late pregnancy,excessive intakes of exogenous hormones,which accelerate the incidence of breast cancer.The incidence of breast cancer in China has the following characteristics:high incidence;The number of young patients increased year by year;Hormone receptor-positive breast cancer rate is higher.According to the immunohistochemical of breast cancer molecular classification,Luminal type belongs to the hormone-dependent breast cancer,which endocrine therapy is the necessary choice.The current status of endocrine therapy for breast cancer:commonly used drug TAM,AIs,and OFS used in high-risk premenopausal patients,all of these drugs reduce the estrogen level and inhibit the growth of tumor cells.In the process of use,adverse reactions can occur,such as hot flashes,upset,insomnia,depression,and so on.According to the results of several clinical studies,the increased time of endocrine therapy will bring long-term benefits to patients.Patients are often faced with 5 to 7 years or even 10 years of treatment time.The severity of these adverse reactions is the main reason to reduce the compliance of endocrine therapy.Some patients have to change drugs or give up endocrine therapy due to prolonged and slow relieved clinical symptoms,thus reducing the survival benefit and affecting the survival period.Base on these characteristics,and according to the rapid development of our country's economic level,the national cultural connotation of ascension,the influx of patients with young people,in the process of long-term against recurrence of breast cancer metastasis and patients' growing demand for quality of life,how to mitigate the effects of adverse reaction,increase the compliance of patients to use drugs,so as to achieve the survival benefit,has become a focus in the study of the current treatment.The conventional treatment of modern medicine include general and symptomatic treatment,hormone replacement therapy,the application of plant medicine,etc.Hormone replacement therapy is not widely used in clinical use because of its promoting effect on breast cancer cells.The use of symptomatic treatment to treat bone pain and bisphosphonate alleviates osteoporosis,which can aggravate the economic burden of the patients.On the one hand,the financial burden of the patients is increased.On the other hand,the safety of the use of drugs is still questionable due to adverse reactions,such as mandibular osteonecrosis and kidney injury caused by bisphosphonate.So far,there are no effective methods and drugs in modern medicine to improve the quality of life of breast cancer patients during endocrine therapy.There are many clinical studies on TCM compounds with adverse reactions caused by endocrine therapy for breast cancer.,After summarizing and analyzing multiple literatures,it was found that:Although Chinese medicine treatment can get good effect,it has become an indispensable part of improving the quality of life and alleviating adverse reaction symptoms during endocrine therapy for Luminal type breast cancer patients But these studies still have the following problems.:1.Simple syndrome differentiation was performed only according to clinical symptoms,but the pathogenesis and pathogenesis of breast cancer were not taken into account;2.Currently clinical trials are mostly single-arm non-control,or single-blind,or blind_agnostic clinical trials,Although significant differences can be obtained according to the experimental method,it is not a highly convincing study with a high level of evidence.The therapeutic methods and drugs recorded in the literature have not formed effective drugs and measures for the treatment of adverse reactions caused by endocrine drugs in traditional Chinese medicine;3.Chinese medicine has a good clinical effect,but there are few studies on whether it will affect the proliferation of breast cancer cells while improving the quality of life and alleviating clinical symptoms;4.In the literature,it is reported that the herbal medicine containing phytoestrogens is often included in the TCM compound,several studies have shown that phytoestrogens may stimulate the proliferation of MCF-7 cells in breast cancer cells,while another studies have also shown that phytoestrogens have a concentration dependence on the proliferation of breast cancer cells.Two randomized double-blind studies were reported;while the compound of phytoestrogens alleviates the symptoms,the expression of hormone level is different,which also indicates the mechanism of drug action or other ways.At present,there is still some controversy about the use of the medicine in Wen Yang,which is one of the biggest questions in western medicine about the intervention of TCM in breast cancer;5.In addition,icariin,a traditional Chinese medicine commonly used in the compound,is reported to be hepatotoxic and its safety in long-term use requires long-term clinical observation.In conclusion,traditional Chinese medicine has not been able to develop effective measures and drugs to treat adverse reactions during endocrine period in Luminal breast cancer patients.Our clinical observation shows that:after surgery,radiotherapy and chemotherapy,patients with breast cancer have the basic pathogenesis of liver and kidney deficiency.On this basis,the adverse reactions of Luminal patients during endocrine therapy are mostly "depression syndrome" after disease differentiation.Syndrome differentiation mostly belongs to "qi stagnation,sputum obstruction and blood stuffiness".The clinical manifestations of adverse reactions caused by endocrine drugs are usually associated with shaoyang syndrome We put forward the key points of the treatment of this disease,such as the reconciliation in the surface,the transportation inside and outside,the free flow of qi and blood,the prevalence of tianj in fluid.In recent years,the idea of treating tumors by means of prescriptions has been paid more and more attention.The self-made CGLM soup we used in clinical practice originated from the jing fang,which is a combination of small chai-hu soup,gui-zhi soup,gui-gan-long-mu soup,and banxia houpu soup.It was found that the CGLM decoction could significantly improve the quality of life during endocrine therapy of Luminal breast cancer patients and indirectly improve the drug compliance of endocrine drugs.Through long-term observation,it was found that this compound could avoid inducing the proliferation of breast cancer cells and the recurrence and metastasis of tumors while alleviating the clinical symptoms.Based on this research idea,as the subject in hospital(XYKY-MP(2013)-13)support,which was divided into two parts.The first part:to carry out prospective,exploratory clinical research,using randomized,double-blind,placebo-controlled study method,To observe the improvement of Luminal breast cancer patients' quality of life during endocrine therapy by CGLM,so as to provide evidence for the treatment of adverse reactions caused by endocrine drugs.The second part:The effect of this compound containing serum on human breast cancer MCF-7 cell line was used to observe whether there was a proliferation effect on breast cancer cells while relieving clinical symptoms.Objective1.To observe the effect of CGLM decoction for improving of quality of life during the endocrine treatment of Lumianl breast cancer patients.2.To observe the inhibitory effect of the drug serum CGLM on human breast cancer MCF-7 cell line and the expression of Estrogen receptor alpha.Methods1.CGLM decoction for improving the quality of life during the endocrine treatment of Luminal breast cancer patientsA study protocol for a prospective,randomized,double-blind,placebo-controlled trial,in the end 50 Luminal type patients were enrolled in this study between 2015.11-2017.11 who being randomly allocated to TCM group(treated by CGLM decoction)and control group(treated by Placebo),respectively,both group had conventional treatment.Using one week TCM symptoms score?MDASI-C score before treatment as base line.To compare the improvement of symptoms after treatment.2.Impact Serum containing CGLM decoction on the growth inhibition and Estrogen receptor expression in human breast cell line MCF-7In which that cell line of human breast cancer McF-7 cell line were respectively adjoin to a corresponding(medical-containing)culture medium,in which the control group contained 10%empty rat serum;In which that administration group contain 10%of the CGLM serum of low,medium and high dosage group respectively.After dosing will be at 37 ? and 5%C02 incubator continue to develop in 48 h.MTT assay was used to detect the inhibitory effect of CGLM serum on human breast cancer MCF-7 cell proliferation.Adding 10%CGLM serum culture base MCF-7 cell,incubation after 48 h,cells extracted total mRNA and protein,reverse transcription synthesis of cDNA,by adopting the method of real-time fluorescent quantitative PCR detection of ER alpha mRNA expression level in each cell,using Western bolt methods to detect each ER alpha protein expression.Results1.CGLM decoction for improving the quality of life during the endocrine treatment of Luminal breast cancer patientsA month after treatmentTCM symptom scale score.1.1 Efficiency:TCM group of 25 patients,symptoms improved significantly in 7 cases,partial improvement of 17 cases,there is no improvement in 1 case,significant period was 28%,the part of the period was 68%,total effective rate was 96%,no period was 4%.The placebo group of 23 patients,symptoms improved significantly in 1 case,partial improvement,6 cases,9 cases without improving symptom aggravating in 7 cases,significant period was 4.3%,the part of the period is 26.1%,the total effective rate was 30.4%,no period was 39.1%.1.2 Itself after treatment before and after comparisonThe TCM group symptoms improved with significant difference(P<0.01),the placebo group symptoms improved no statistical difference(P>0.05)?After treatment compared with placebo group,TCM group can improved symptoms,the difference was statistically significant(P<0.01).1.3 Furthermore,repeated measurement of ANOVA showed that the score of TCM symptoms:after treatment compared with placebo group,TCM group was improved the symptoms significantly(P<0.01).1.4 Comparison of TCM symptom scores after each symptom was administered.In 17 symptoms,the TCM group obviously alleviate the night sweats,spontaneous perspiration,joint pain and other symptoms(P<0.05,P<0.001).The three symptoms of stress,fatigue and tinnitus were relieved by the TCM group,but there was no statistical difference(P>0.05).It also was found that that control group had a relief effect on the symptom of hot flashes and had significant difference(P<0.05).1.5 Compared with before treatment,the MDASI-C score in the TCM group decreased significantly,and the quality of life was significantly improved,with statistical difference(P<0.01).The score of MDASI-C in the control group was decreased,with no statistical difference(P>0.05).The MDASI-C scores of the two groups were both lower than those before administration,but no significant difference(P=0.077>0.05).1.6 Subgroup analysis:1.6.1 Into the case according to the age group,can be divided into less than or equal to 49 years old and more than 49 years old in the two groups.Compared with younger patients,more than 49 revenue groups more performance for depression.bitter taste,with statistical difference(P<0.05).Compared with before treatment,the clinical symptoms of the TCM group were significantly reduced regardless of any age(P<0.05,P<0.01).After traditional Chinese medicine treatment,compared with the placebo group,the patients older than 49 showed obvious relief of night sweats,self-sweating,hot flashes,fatigue and symptoms,with significant differences(P<0.05,P<0.01).1.6.2 The included cases were divided into pre-and post-menopause groups according to whether they were postmenopausal.Compared with the before treatment,the difference of TCM symptom score in the TCM group was statistically significant(P<0.01),regardless of postmenopausal status.Compared with the placebo group,the scores of TCM symptoms of postmenopausal patients in the TCM group decreased significantly,with a statistically significant difference(P<0.01).Compared with the placebo group,postmenopausal patients in the TCM group could significantly alleviate the symptoms of flank pain(P<0.05).Compared with the placebo group,postmenopausal patients in the TCM group after treatment can significantly relieve the symptoms of five symptoms of perturbed fever,self-perspiration,hot.flashes,mental fatigue and bitter taste,with statistical signi:ficance(P<0.05,P<0.01).2.Impact Serum containing CGLM decoction on the growth inhibition and Estrogen receptor expression in human breast cell line MCF-72.1 MTT results showed that compared with the control group,the low.medium and high dose group of the CGLM could inhibit the proliferation of MCF-7 cells,medium and high dose groups were statistical difference(P<0.01),2.2 qPCR detection:compared with the control group,the levels of ER alpha mRNA in the low,medium and high dose group of CGLM stun were all increased,among which the high-dose group was significantly different(P<0.01).2.3 Western bolt method was used to detect that,compared with the control group,the low,medium and high dose groups in the CGLM had increased the expression of ER alpha protein,the medium and high dose groups with significant difference group(P<0.01).Conclusions1.The prospective,randomized,double-blind,placebo-controlled study method,through selecting scale of TCM symptoms,quality of life and physical status score,it is concluded that:CGLM effectively improve the quality of life during the endocrine treatment of Luminal breast cancer patients,reduce the related adverse reactions of endocrine therapy,and have no adverse reactions during the follow-up period,and cooperate with endocrine therapy to show good compliance with medication compliance.2.CGLM decoction has a certain inhibitory effect on the growth of McF-7 cells,and is positively correlated with the dose concentration,and its mechanism may be related to the increase of the content of ER alpha mRNA and the up-regulated expression of ER alpha... |
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