| Background and ObjectiveBreast cancer is one of the most common cancers in women. For thepremenopausal patients, most combination chemotherapies produce eithercomplete menopause or at least some degree ofovarian dysfunction.There is much controversy surrounding the prognostic value ofchemotherapy-induced menopause to breast cancer. But the side effects ofmenopause too earlier are obvious. In breast cancer survivors, theexperience ofthe abrupt onset of menopausal symptoms is a major problem.In breast cancer patients treated with chemotherapy, the menopauseoccurs abruptly, and symptoms such as hot flash and night sweats can be moresevere than those normal menopausal women. And these acute menopausalsymptoms, which are added to the anxieties, symptoms, and concerns alreadyassociated with the diagnosis of breast cancer and its surgical,chemotherapeutic, or hormonal therapy, obviously impair the quality of lifeof breast cancer patients. But how to treat the range of problems relatedto estrogen deficiency in these patients is largely unexplored at the presenttime. Based on much that we know about the causes and treatment of breastcancer, a traditional belief of the medical profession holds that estrogenand/or progesterone therapy in women surviving breast cancer poses anunacceptable risk. Thus, both physicians and patients remain extremelycautious about the routine clinical use of estrogen or progesterone in women who have ever had a diagnosis of breast cancer.Tamoxifen, an ER modulator, is an effective antitumor agent for advancedbreast cancer in cycling premenopausal women. Conceptson the stoichiometrybetween tamoxifen and estrogen for the estrogen receptor and thedifferential agonistic and antagonistic effects of tamoxifen on varioustarget tissues were formally presented. It was noted that the combinationof tamoxifen with estrogen or progesterone might potentially relievemenopausal symptoms without increasing the risk of tumor recurrence. However,the data presented were insufficient to conclude that symptoms would be fullyrelieved by this approach. And the large randomized, controlled trialsshould be performed to ensure its safety and efficacy.On the other hand, it was proved that traditional Chinese medicine hasa good clinical effectiveness to treat perimenopausal syndrome during the longterm clinical observation. Erxian decoction, a famous traditional reinforcingkidney formula for perimenopausal syndrome, is composed of Urculigo orchioides,Epimedium, Morinda officinalis, Angelica sinensis, and Anemarrhena andPhellodendron amurense. After repeated filtered and validated in clinic forseveral decades, it has gradually become the representative prescription totreat menopausal syndrome, Urculigo orchioides and Epimedium are monarch drugsin Erxian decoction and also common used herbs in treating perimenopausalsyndrome. But the mechanism of Erxian decoctionand its monarch drugs appliedin ovarian dysfunction remains unclear and information in the literature islimited in regards to tissue uptake and metabolism. Considered theconstituents of Erxian decoction maybe have estrogen-like activity, whetherit will increase the risk of tumor recurrence when relieving menopausalsymptoms of postoperative breast cancer patients and inhibit its stimulatingaction to breast cancer cell when combined with tamoxifen should be studiedfurther.The purpose of this study was to test the efficacy of Erxian decoction inchemotherapy induced amenorrhea of breast cancer survivors and to explore theeffects of its monarch drugs Urculigo orchioides and Epimedium alone orcombined with tamoxifen on the proliferation and apoptosis of breast cancerMCF-7 cells. Partâ… The Effect of Erxian Decoction in Chemotherapy Induced Amenorrhea ofBreast Cancer.Objectives:To evaluate the efficacy of two different therapies and formulas for thetreatment of menopausal symptoms in breast cancer survivors.Methods:A retrospective controlled clinical study. 151 patients witha historyof breast cancer, recruited from a breast cancer database, who. had completedall surgery, chemotherapy, and/or radiation treatment were included in thisstudy. Subjects received either reinforcing kidney therapy (Erxian decoction)or reinforcing Qi therapy (sijunzi decoction) for six months. Follow up was2 years. The number and time of the reappearance of regular menstruation werecompared between two groups. And scores on a composite menopausal symptom scalewas compared too. Descriptive statistics were used to analyze the quantitativedata, Student' s t-tests and Cox proportional hazards regression model wereperformed for statistical analysis using the Spss package (11.5 for windows).All tests were two sided; a difference was considered significant at a P levelof 0.05.Results:The number of resumption menstruation in reinforcing kidney group are50(61.7%) and 39(55.7%) in reinforcing Qi group. The result of Cox modelrevealed the principle factors of influencing menstruation recovering are age,different therapeutic methods and chemotherapy regimens. Adjusted for age andchemotherapy regimen, the odds rate of reappearance of regular menstruationis 2.46 [1.538, 3.929] in reinforcing kidney group compared to reinforcing Qigroup. But there was no significant difference between two groups in theaverage time of recovering menstruation since chemotherapy induced amenorrhea(p＞0.05). In the alleviating the menopause symptom of hot flash, night sweatsand anxiety mood, a statistically significant improvement in reinforcingkidney group than reinforcing Qi group. But in symptom of fatigue and dizziness,there were a positive trend in the reinforcing Qi group. No significant change in the symptom of depression, insomnia and arthralgia (p＞0.05).Conclusions:The results from this retrospective trial suggest that traditional Chinesemedicine may be of value in the treatment of menopausal symptoms and improvingquality of life, especially Erxian decoction was prescribed to those womenwith symptoms of hot flash, sweats and anxiety, but the chance of resumptionmenstruation was increased. This study was design to compare the effectivenessof different therapeutic methods in menopausal symptoms of breast cancersurvivor. It maybe give a hint that compared with placebo, the reinforcingkidney method has a similar trend in reducing menopausal symptoms. But largesample, multi-central and randomized controlled studies or well designedcohort studies should be carried out and long term follow up should be performedso as to evaluate the efficacy and safety of Erxian decoction, the reinforcingkidney formula, applied to breast cancer survivor.Partâ…¡Effect of Urculigo Orchioides and Epimedium on the Proliferation andApoptosis of Human Breast Cancer Cells MCF-7 in VitroObjective:The aim of the study was to explore the effects of Urculigo orchioidesand Epimedium on the proliferation and apoptosis of breast cancer MCF-7 cells.Materials and methods:Human estradiol-dependent breast cancer MCF-7 cells were grown in RPMI1640medium, containing 10% bovine serum. Four days before addition of the testcompounds, the cells were washed with phosphate-buffered saline, and thencultured in phenol red-free 1640 medium. The different doses of Urculigoorchioides and Epimedium alone and combined with tam were added into theculture medium, and 17β-estradiol, tamoxifen were also added to culture mediumas control groups. The MTT assay was used to evaluate the proliferation ofMCF-7 under the different conditions of interventions. Cell apoptotic ratewere measured with flow-cytometry and Annexin v-PI staining. Cellular morphologic changes were observed using transmission electron microscopy.Data are expressed as mean±standard deviation (SD), and a one-way ANOVA wasperformed for each group. All statistical tests were two-sided and p＜0.05was considered to indicate statistical significance.Results:The influences of cell growth were different with the differentconcentrations of Urculigo orchioides and Epimedium. Based on the cell growthcurve, the effect Urculigo orchioides and Epimedium on the growth of breasttumor cells was biphasic. But the stimulatory effect of Urculigo orchioideswas weak and there is no significant differences between Urculigo orchioidesgranule and serum with the blank control (p＞0.05). 10-6mol/l Epimedium couldincrease the proliferation of MCF-7 cells but the effect is weaker than17β-estradiol. When the concentration of Urculigo orchioides and Epimediumare higher than 10-5mol/l, the cell growth were markedly inhibited and theinhibition rate were dose dependent. Epimedium shows little stimulatory effecton the proliferation of MCF-7 when its concentration is lower than 10-7mol/l(p＞0.05). Urculigo orchioides and Epimedium of various concentrationscombined with tam show no effect on the proliferation of breast cancer cells.On the other hand, Urculigo orchioides and Epimedium could cause profoundinhibition of growth of MCF-7 at higher doses. 20% Urculigo orchioides andEpimedium serum combined with tam or Epimedium serum alone can induce apoptosisand the effects were dose-dependent.ConclusionsThese data suggest that Urculigo orchioides and Epimedium combined withtam have no significant effect on the proliferation of MCF-7 cells; the higherdose Epimedium even has the ability to induce apoptosis of breast cancer cells.On the other hand, Epimedium at the concentration of 10-6mol/l maybe haveestrogen-like activity but can be inhibited by TAM. The results of the studycan provide experimental evidence for Urculigo orchioides and Epimediumapplied in breast cancer survivors and suggest that Urculigo orchioides andEpimedium are safety to be used in clinic, especially in those women with ER(+)and receiving therapy of TAM. But the further studies should be carried outabout correct usage include dosage and duration and so on. The result from this trial suggest that Erxian decoction may be of valuein the treatment of menopausal symptoms and recovering of menstruations ofbreast cancer survivors, especially in those with estrogenreceptor-positive tumorswho take tamoxifen at the same time and the results of Urculigo orchioides andEpimedium on the proliferation and apoptosis of breast cancer MCF-7 cellssuggest that Urculigo orchioides and Epimedium or combined with TAM are safeto be usedto treat chemotherapy-induced amenorrhea of breast cancer patients.Accordingly, this study provides theoretical foundation for reinforcingkidney Erxian decoction and its components applied in breast cancer patients.
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