Introduction The figures released by International Agency for Research on Cancer show that breast cancer is one of the most common cancers (DeSantis et al., 2014), and the most common malignant tumor for women patients, with the rising mortality rate year by year. At present, the annual growth rate of breast cancer incidence in China is 3-4%, higher than the average one of global growth. Meanwhile the onset age of breast cancer of Chinese women is less than that of Western women (Hong-Li et al., 2014). In clinical practice, chemotherapy is an important therapy method, but prone to cause cancer metastasis and serious adverse reactions which influence the quality of life of patients, and therefore it is necessary to find a suitable therapy method for breast cancer specific to Chinese women patients (Gielen et al., 2005). Goserelin is a synthetic analogue of a naturally occur- ring luteinizing-hormone releasing hormone, which is studied most widely for treating premenopausal patients of breast cancer, and it is a very efficient kind of medicine for endocrine therapy with little toxic effect, which inhibits the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and forms a reversible inhibition of the secretion of FSH and LH, to achieve the hypophysectomy effect of selective drugs and the overall suppression of ovarian function, so that the estrogen levels of premenopausal women reach the ones of postmenopausal women to inhibit the tumor- growth-promoting effect of estrogen (Liu et al., 2013; Yang et al., 2013). Therefore, goserelin is commonly used in the adjuvant therapy of premenopausal breast cancer patients, and for the patients with estrogen receptor-positive lymph node metastasis, the same effect can be obtained as chemotherapy. A Journal of the Bangladesh Pharmacological Society (BDPS) Bangladesh J Pharmacol 2015; 10: 988-996 Journal homepage: www.banglajol.info Abstracted/indexed in Academic Search Complete, Agroforestry Abstracts, Asia Journals Online, Bangladesh Journals Online, Biological Abstracts, BIOSIS Previews, CAB Abstracts, Current Abstracts, Directory of Open Access Journals, EMBASE/Excerpta Medica, Google Scholar, HINARI (WHO), International Pharmaceutical Abstracts, Open J-gate, Science Citation Index Expanded, SCOPUS and Social Sciences Citation Index; ISSN: 1991-0088 Abstract This study aims to evaluate the efficacy and safety of goserelin combined with chemotherapy for premenopausal women with breast cancer. Literatures were extracted from databases including Excerpta Medica Database, Springer, Pubmed, China National Knowledge Infrastructure and Chinese Biological Medicine from their inception up to May 2014. The main efficacy measures were 5 years overall survival (OS), 10 years OS, 5 years disease free survival and 5 years progress free survival. Ten randomized comparison clinical trials were eligible in this study. The result showed that goserelin combined with chemotherapy group can improve the survival rate and decrease the incidence of arthralgia in postmenopausal breast cancer patients, respectively, compared to the control group. However, they can increase the occurrence of vomiting during the chemotherapy process. Compared with the simple chemotherapy, goserelin combined with chemotherapy can provide benefits for premenopausal women with breast cancer on improving the survival rate and reducing arthralgia. Article Info Received: 14 July 2015 Accepted: 14 August 2015 Available Online: 27 November 2015 DOI: 10.3329/bjp.v10i4.24198 Cite this article: Wang Y, Zhu ZF, Pan WJ, Xu Z. Effi- cacy and safety of goserelin combined with adjuvant chemotherapy in premenopausal women with breast cancer. Bangladesh J Pharmacol. 2015; 10: 988-96. Efficacy and safety of goserelin combined with adjuvant chemotherapy in premenopausal women with breast cancer Yang Wang1, Zheng Fei Zhu1, Wei Jun Pan2 and Zhe Xu1 1Department of Pharmacy, Maanshan Municipal Health Hospital For Women And Children, Maanshan, Anhui 243 000, China; 2Obstetrics, Maanshan Municipal Health Hospital For Women And Children, Maanshan, Anhui 243 000, China. M et a- an al ys is file:///C:/Users/AIM/Desktop/24198-87067-1-RV%20\(1\).doc#_ENREF_7#_ENREF_7 file:///C:/Users/AIM/Desktop/24198-87067-1-RV%20\(1\).doc#_ENREF_12#_ENREF_12 file:///C:/Users/AIM/Desktop/24198-87067-1-RV%20\(1\).doc#_ENREF_9#_ENREF_9 file:///C:/Users/AIM/Desktop/24198-87067-1-RV%20\(1\).doc#_ENREF_16#_ENREF_16 file:///C:/Users/AIM/Desktop/24198-87067-1-RV%20\(1\).doc#_ENREF_23#_ENREF_23 http://www.bioxbio.com/if/html/BANGL-J-PHARMACOL.html Currently, a large number of clinical studies in gose- relin have been reported. But there are obvious differences because the size of a single test sample is too small, and interventions and results index adopted in each study are inconsistent. Meta-analysis is applied in this study to comprehensively evaluate the treatment of goserelin combined with chemotherapy for premeno- pausal women patients, providing more reliable medical evidence for clinical application. Materials and Methods Identification of eligible studies Literatures were extracted from databases including Excerpta Medica Database (EMBASE)，Springer, PubMed, China National Knowledge Infrastructure (CNKI) and Chinese Biological Medicine (CBM) from their inception up to May 2014. The search terms were used as follows: ‘Goserelin’, ‘zoladex’, ‘chemotherapy’ and ‘premenopausal women with breast cancer’. Inclusion and exclusion criteria Inclusion criteria include a) randomized clinical trial (RCT); b) premenopausal women with breast cancer; c) the treatment with goserelin combined chemotherapy. Exclusion criteria include a) male breast cancer patients; b) different endpoint or other types of breast diseases; c) patients had previously subjected to chemotherapy, radiotherapy or surgery; d) concurrent infection; e) other malignancy or serious medical illnesses. Data extraction In order to maintain uniformity and reduce potential reporting bias, two independent reviewers extracted data using a standardized collection according to the inclusion and exclusion criteria listed earlier from those databases. The following characteristics were extracted from each study: name of first author, year of publica- tion, location in which the studies were performed, total number of cases and controls, methods of randomiza- tion, intervention and treatment duration. If there were discrepancies in all cases, they were discussed between the reviewers before a final consensus was reached. Disagreements were resolved by the third author. Statistical analysis Meta-analysis was performed according to the Coch- rane Handbook for Systematic Reviews of Interven- tions. The pooled relative ratio (RR) and 95% confi- dence interval (CI) were used to assess efficacy and safety endpoints. Heterogeneity was analyzed using the I2 statistic: I2 = 100% × (Q-df)/Q. I2 of 0–25% was con- sidered to not have heterogeneity; I2 of 25–50% may represent low heterogeneity; I2 of 50–75% may repre- sent moderate heterogeneity; and I2 of 75–100% indi- cate high heterogeneity (Ai et al., 2014; Lyu et al., 2014). When no heterogeneity or low heterogeneity was pre- sent, the fixed effects model was used for meta-analysis (Chai and Liu, 2014). When moderate heterogeneity or high heterogeneity was present, the fixed effects model was compared to the random effects model of DerSimonian–Laird (Higgins and Thompson, 2002). Publication bias was assessed using funnel plots with visual inspection of asymmetry. RR, tests for hetero- geneity, and forest plots for the relevant comparisons were performed using STATA 12 with Beggr's bias test and Egger’s bias test, with p≤0.05 indicating potential bias (Yang et al., 2013).2013). Results Eligible studies 1644 publications were initially identified, 1634 studies were excluded, as they were review papers contained no original data, or a reanalysis of data, or measured deferent endpoints, and/or had no control group. Finally, 10 studies (Baum et al., 2006; Castiglione- Gertsch et al., 2003; Cheng et al., 2012; Davidson et al., 2005; Gerber et al., 2011; Hackshaw et al., 2009; Karlsson et al., 2011; Kaufmann et al., 2007; Kaufmann et al., 2003; von Minckwitz et al., 2006) with a total sample population of 11171 patients (5433 in the treatment group and 5738 in the control group) were identified based on the inclusion/exclusion criteria (Figure 1). Characteristics of studies included in the current meta- analysis were presented (Table I). Quality assessment All RCTs mentioned random allocation, 8 studies reported and described random allocation methods. None of the studies described the blind method. These RCTs design all include a baseline assessment including patients’ age, stage of disease, etc. No significant differences were found between the baseline data. In these RCTs, three combination chemotherapies have been performed to treat advanced breast cancer: one study used CAF; seven studies used CMF; and the other studies used chemotherapy (Table I). Meta-analysis The main treatment efficacy indicators considered in meta-analysis are: a) 5 years overall survival (OS); b) 10 years OS; c) 5 years disease free survival (DFS); d) 5 years progress free survival (PFS); The indicators for the safety of the treatments are mainly the rate of occurrence of emesis and arthralgia. 5 years OS of patients Ten clinical trials evaluated the 5 years OS of patients. Heterogeneity was considered absent at the I2 statistic (I2 = 2%, p = 0.42). A fixed effects model was performed on outcome measurements. The results show that goserelin combined with chemotherapy could Bangladesh J Pharmacol 2015; 10: 988-996 989 significantly increase the efficacy of 5 years OS in premenopausal women with breast cancer (RR = 1.07; 95% CI [1.05, 1.09], p<0.00001), compared to the control group (Figure 2). Ten years OS of patients Ten clinical trials evaluated the 10 years OS of patients. Heterogeneity was considered absent at the I2 statistic (I2 = 7%, p = 0.36). A fixed effects model was performed on outcome measurements. The results show that gose- relin combined with chemotherapy could significantly increase the efficacy of 10 years OS in premenopausal women with breast cancer (RR = 1.10; 95% CI [1.07, 1.14], p<0.00001), compared to the control group (Figure 3). Ten years DFS of patients Ten clinical trials evaluated the 10 years DFS of pati- ents. Heterogeneity was considered absent at the I2 statistic (I2 = 41%, p = 0.15). A fixed effects model was performed on outcome measurements. The results show that goserelin combined with chemotherapy could significantly increase the efficacy of 5 years DFS in premenopausal women with breast cancer (RR = 1.10; 95% CI [1.07, 1.14], p<0.00001) , compared to the control group (Figure 4). Five years PFS of patients Ten clinical trials evaluated the 5 years PFS of patients. Heterogeneity was considered absent at the I2 statistic (I2 = 0%, p = 1.00). A fixed effects model was performed on outcome measurements. The results show that gose- relin combined with chemotherapy could significantly increase the efficacy of 5 years PFS in premenopausal women with breast cancer (RR = 1.11; 95% CI [1.08, 1.14], p<0.00001), compared to the control group Figure 1: Flow diagram of study identification Table I Baseline characteristics of the eligible trials Study Sample size (case/control) Age Intervention group Treatment duration Random alloca- tion method Year Test Control Nancy E. Davidson 502/494 Unclear G + CAF CAF 28 days Random number 2005 Manfred Kaufmann 224/241 Clear G + CMF CMF 4 weeks Random number 2007 M. Baum 1356/1354 44/44 G + CMF CMF 4 weeks Random number 2006 Gunter von Minckwitz 378/393 45/45 G + CMF CMF 4 weeks Mention 2006 M. Kaufmann 817/823 Unclear G + CMF CMF 4 weeks Random number 2003 W. Jonat 733/753 Clear G + CMF CMF 28 days Random number 2002 Monica C. Gertsch 357/360 Unclear G + CMF CMF 4 weeks Random number 2003 P. Karlsson 282/292 Unclear G + CMF CMF 4 weeks Random number 2011 Tsui Fen Cheng 152/412 42.6/45.6 G+C C 4 weeks Mention 2012 Allan Hackshaw 469/476 40.8/41.9 G+C C 28 days Random number 2009 G: GOS; C: chemotherapy; CAF: cyclophosphamide, doxorubicin, and fluorouracil; CMF: cyclophosphamide, methotrexate, and 5-fluorouracil Excluded after reading the full text (n=418)  Inconsistent data (n=5)  Non-RCT (n=382)  Failure to meet inclusion criteria (n=31)  Duplicated publications (n=3) Initial search (n=1585) EMBASE (n=26), PubMed (n=327), CNKI (n=443), Springer (n=789), CBM (n=19) Publications excluded after screening the title and abstract (n=1158) Next RCTs (n=427) Final RCTs (n=6) 990 Bangladesh J Pharmacol 2015; 10: 988-996 reduce arthralgia in premenopausal women with breast cancer (RR = 0.70; 95% CI [0.50, 0.96], p = 0.03), compared to the control group (Figure 7). Publication bias The shape of the funnel plot for the homozygote comparison appeared to some asymmetry and no obvious bias in this meta-analysis, suggesting the possibility of publication bias (Figure 8). Publication bias was assessed by Begg’s test and Egger’s test (Table II). No publication biases were observed except when comparing the efficiency of combination group and chemotherapy group on 5 years DFS (p-value [Begg’s]: 0.023, p-value [Eegg’s]: 0.003). It showed a potential publication bias might caused by a language bias, inflated estimates by a flawed methodological design in smaller studies, and/or a lack of publication of small trials with opposite results. Figure 2: Meta-analysis of 5 years OS Figure 3: Meta-analysis of 10 years OS (Figure 5). Emesis of patients Three clinical trials evaluated the emesis of patients. Heterogeneity was considered absent at the I2 statistic (I2 = 18%, p = 0.30). A fixed effects model was performed on outcome measurements. The results show that gose- relin combined with chemotherapy could significantly increase the incidence rate of emesis of premenopausal women with breast cancer (RR = 2.01; 95% CI [1.34,3.00], p = 0.0007), compared to the control group (Figure 6). Arthralgia of patients Three clinical trials evaluated the arthralgia of patients. Heterogeneity was considered absent at the I2 statistic (I2 = 0%, p = 0.46). A fixed effects model was performed on outcome measurements. The results show that gose- relin combined with chemotherapy can significantly Allan Hackshaw 2009 422 469 405 476 9.0% 1.06 [1.01,1.11] Gunter von Minckwitz 2006 373 393 329 378 7.5% 1.09 [1.04,1.14] M. Baum 2006 1093 1354 1038 1356 23.1% 1.05 [1.01,1.10] M. Kaufmann 2003 617 735 571 758 12.5% 1.11 [1.06,1.17] Manfred Kaufmann 2007 340 384 332 392 7.3% 1.05 [0.99,1.10] Monica C. Gertsch 2003 339 357 324 360 7.2% 1.06 [1.01,1.10] Nancy E. Davidson 2005 437 502 420 494 9.4% 1.02 [0.97,1.08] P. Karlsson 2011 332 354 311 389 6.9% 1.08 [1.03,1.14] Tsui Fen Cheng 2012 137 152 334 412 4.0% 1.11 [1.04,1.19] W. Jonat 2002 616 733 589 753 13.0% 1.07 [1.02,1.13] Study or Subgroup Events Total Events Total Weight M.H, Fixed, 95% CI M.H, Fixed, 95% CI Total (95% CI) 5433 5738 100.0% 1.07[1.05,1.09] Total events 4706 4653 Heterogeneity: Chi2= 9.22, df= 9 (p=0.42); I2= 2% Test for overall effect: Z= 7.99 (p<0.00001) 0.5 0.7 1 1.5 2 Control beneficial Experimental beneficial Experiment group Control group Risk Ratio Risk Ratio Allan Hackshaw 2009 385 469 342 476 18.4% 1.14 [1.06,1.23] M.Baum 2006 1085 1356 980 1354 53.3% 1.11 [1.06,1.15] Nancy E. Davidson 2005 359 502 340 494 18.6% 1.04 [0.96,1.13] Tsui Fen Cheng 2012 136 152 330 412 9.7% 1.12 [1.04,1.20] Study or Subgroup Events Total Events Total Weight M.H, Fixed, 95% CI M.H, Fixed, 95% CI Total (95% CI) 2479 2736 100.0% 1.10 [1.07,1.14] Total events 4706 4653 Heterogeneity: Chi2= 3.21, df= 3 (p=0.36); I2= 7% Test for overall effect: Z= 6.12 (p<0.00001) 0.5 0.7 1 1.5 2 Control beneficial Experimental beneficial Experiment group Control group Risk Ratio Risk Ratio Bangladesh J Pharmacol 2015; 10: 988-996 991 app:ds:incidence app:ds:rate javascript:void\(0\); Figure 4: Meta-analysis of 5 years DFS Figure 5: Meta-analysis of 5 years PFS Table II Meta-analysis on efficacy and safety of GOS combined with chemotherapy Study Indicator Numberof trials Combined effect size Heterogeneity Publication bias RR 95%CI Mode I2(%) p-Value p-Value (Begg’s) p-Value (Eegg’s) Test of efficiency 5 years OS 10 1.07 1.05-1.09 F 2 0.42 0.421 0.323 10 years OS 4 1.10 1.07-1.14 F 7 0.36 0.500 0.233 5 years DFS 5 1.10 1.07-1.14 F 41 0.15 0.023 0.003 5 years PFS 4 1.11 1.08-1.14 F 0 1.00 0.308 0.062 Test of safety emesis 3 2.01 1.34-3.00 F 18 0.30 0.602 0.410 arthralgia 4 0.70 0.50-0.96 F 0 0.46 0.734 0.225 Study or Subgroup Events Total Events Total Weight M.H, Fixed, 95% CI M.H, Fixed, 95% CI Total (95% CI) 2479 2721 100.0% 1.12 [1.08,1.15] Total events 1982 1802 Heterogeneity: Chi2= 6.81, df= 4 (p=0.15); I2= 41% Test for overall effect: Z= 6.30 (p<0.00001) 0.5 0.7 1 1.5 2 Control beneficial Experimental beneficial Experiment group Control group Risk Ratio Risk Ratio M. Kaufmann 2003 482 735 433 758 23.8% 1.15 [1.06,1.24] Monica C. Gertsch 2003 321 357 302 360 16.8% 1.07 [1.01,1.13] Nancy E. Davidson 2005 377 502 321 494 18.1% 1.16 [1.06,1.25] P. Karlsson 2011 320 350 303 351 16.9% 1.06 [1.00,1.12] W. Jonat 2002 482 735 443 758 24.4% 1.12 [1.04,1.22] Gunter von Minckwitz 2006 362 393 314 378 17.0% 1.11 [1.05,1.17] M.Baum 2006 1056 1354 949 1356 50.4% 1.11 [1.07,1.17] Manfred Kaufmann 2007 302 384 279 392 14.7% 1.10 [1.02,1.20] Nancy E. Davidson 2005 377 502 336 494 18.0% 1.10 [1.02,1.19] Study or Subgroup Events Total Events Total Weight M.H, Fixed, 95% CI M.H, Fixed, 95% CI Total (95% CI) 2633 2620 100.0% 1.11 [1.08,1.14] Total events 2097 1878 Heterogeneity: Chi2= 0.06, df= 3 (p=1.00); I2= 0% Test for overall effect: Z= 6.69 (p<0.00001) 0.5 0.7 1 1.5 2 Control beneficial Experimental beneficial Experiment group Control group Risk Ratio Risk Ratio 992 Bangladesh J Pharmacol 2015; 10: 988-996 Discussion As a hormone-dependent malignant tumor, breast cancer is a serious threat to women’s health, of which the incidence rate is increasing (Nishimura et al., 2013). Breast tumor cells are influenced by hormone levels in the processes of growth and proliferation. It is found from researching that the incidence, the development and prognosis as well as the therapy effect of breast cancer are closely correlated with the expressions of the estrogen receptor and progesterone receptor. Goserelin is a synthetic analogue of a naturally occurring luteinizing-hormone releasing hormone, and the long-term use can inhibit the luteinizing-hormone secretion of pituitary, thus causing a decline in male serum testosterone and female serum estradiol (Nishimura et al., 2013; Zhou et al., 2013). After 21 days from the initial medical treatment for female patients, serum estradiol concentration is inhibited, which maintains in postmenopausal level during each 28-day treatment thereafter. This inhibition is related to hormone-dependent breast cancer and endometriosis. There may be some symptoms such as flushing, sweating and loss of libido appearing in female patients, and generally it is not necessary to stop the medicine. Headaches and mood changes such as depression may also be seen, as well as vaginal dryness and changes in breast volume. Patients with breast cancer will suffer from the intensified symptoms in the early stage of having the medicine. An extremely small number of patients suffering from endometriosis enter menopause, and their menses will not be recovered after stopping the analogue of luteinizing-hormone releasing hormone (Mills et al., 2005). From the study of this paper, it is found that goserelin combined with chemotherapy can improve the survival rate and decrease the incidence of arthralgia in post- menopausal breast cancer patients during the chemo- therapy process. However, they can increase the occu- rrence of vomiting in postmenopausal breast cancer patients during the chemotherapy process, which is notable. These characteristics indicate researching direc- Figure 6: Meta-analysis of emesis Figure 7: Meta-analysis of arthralgia M. Baum 2006 9 134 2 137 6.0% 4.60 [1.01,20.90] Manfred Kaufmann 2007 1 384 2 392 6.0% 0.51 [0.05,5.61] Nancy E. Davidson 2005 57 50 29 494 88.1% 1.93 [1.26,2.97] Study or Subgroup Events Total Events Total Weight M.H, Fixed, 95% CI M.H, Fixed, 95% CI Total (95% CI) 1020 1023 100.0% 2.01 [1.34,3.00] Total events 67 33 Heterogeneity: Chi2= 2.44, df= 2 (p=0.30); I2= 18% Test for overall effect: Z= 3.40 (p<0.00001) 0.001 0.1 1 10 1000 Control beneficial Experimental beneficial Experiment group Control group Risk Ratio Risk Ratio M. Baum 2006 2 134 6 137 7.0% 0.34 [0.07,1.66] Monica C. Gertsch 2003 7 357 11 360 13.0% 0.64 [0.25,1.64] Nancy E. Davidson 2005 41 502 48 494 57.4% 0.84 [0.56,1.25] W. Jonat 2002 9 802 19 802 22.5% 0.47 [0.22,1.04] Study or Subgroup Events Total Events Total Weight M.H, Fixed, 95% CI M.H, Fixed, 95% CI Total (95% CI) 1795 1793 100.0% 0.70 [0.50,0.96] Total events 59 84 Heterogeneity: Chi2= 2.59, df= 3 (p=0.46); I2= 0% Test for overall effect: Z= 2.19 (p<0.03) Control beneficial Experimental beneficial Experiment group Control group Risk Ratio Risk Ratio 0.001 0.1 1 10 1000 Bangladesh J Pharmacol 2015; 10: 988-996 993 file:///C:/Users/AIM/Desktop/24198-87067-1-RV%20\(1\).doc#_ENREF_20#_ENREF_20 file:///C:/Users/AIM/Desktop/24198-87067-1-RV%20\(1\).doc#_ENREF_20#_ENREF_20 file:///C:/Users/AIM/Desktop/24198-87067-1-RV%20\(1\).doc#_ENREF_25#_ENREF_25 file:///C:/Users/AIM/Desktop/24198-87067-1-RV%20\(1\).doc#_ENREF_18#_ENREF_18 Figure 8: Funnel plot of the studies comparing the efficiency. 5 years OS (A); 10 years OS (B); 5 years DFS (C); 5 years PFS (D); emesis (E); arthralgia (F) 0.5 0.7 1 1.5 2 0 0.02 0.04 0.06 0.08 0.01 SE (log[RR]) 0.5 0.7 1 1.5 2 0 0.02 0.04 0.06 0.08 0.01 SE (log[RR]) A B RR RR C 0 0.02 0.04 0.06 0.08 0.01 0.5 0.7 1 1.5 2 0 0.02 0.04 0.06 0.08 0.5 0.7 1 1.5 2 RR RR SE (log[RR]) SE (log[RR]) D E 0 0.5 1 1.5 2 0.001 0.1 1 10 1000 RR SE (log[RR]) 0.001 0.1 1 10 1000 0 0.2 0.4 0.6 0.8 1 F SE (log[RR]) RR 994 Bangladesh J Pharmacol 2015; 10: 988-996 tion of goserelin combined with chemotherapy. But the symptoms may also be caused by the small sample size of this experiment, which is expected to be improved in the future. The number of people studied as research objects is up to 2710, and 465 at least; the study of which the sample size is too small may achieve the low accuracy of the test result, with the increased incidence rated of type II error, which is the inadequacy of this study (Moher et al., 2012). The average number of cases in experimental group is 54.3, while the average number of cases in control group is 573.8; the research objects in both groups are premenopausal breast cancer patients. And the numbers of objects in all studies are more than 100, but two of them include the estimation of sample size. All RCTs included in this study describe specific stochastic approach. In three papers, hide methods of allocation have been reported, and there are seven papers in the literature have mentioned double-blind method, but have not adopted intention principles of treatment for data analysis. Hide allocation plan is equally important for the prevention from bias and randomization, and the allocation without hide can make the effect of the intervention exaggerated by 30- 41% on average (Karlsson et al., 2011), which is a deficiency in this study. All the previous studies made a comparison of the baseline information on pathological grading and staging, treatment programs of the patients, of which the results showed comparability of baseline between experimental and control groups (p> 0.05). Very few papers are included in the study of this paper as literature. The monitoring intervention for adverse medicine reactions is very significant for the evaluation of the medicine efficacy and clinical medicine administration. However, few reports included in the study mentioned adverse reactions, indicating that the researchers did not pay sufficient attention to the observation and the report of adverse reactions, which is not helpful to the promotion and application of goserelin combined with chemotherapy treatment of premenopausal breast cancer. Conclusion In this study, for the process of goserelin combined with chemotherapy treatment of pre-menopausal breast cancer patients, full consideration should be given to the rudimentary status of the disease, since disease category, disease condition, assessment of nutritional status, physical condition, comorbidities, complications, and the degree of primary disease are all the main factors affecting the treatment. Comparability of studied baseline should be guaranteed, research design should be standardized further, and RCTs should be reported particularly in accordance with CONSORT standard (Schulz et al., 1995). Future research will be more concerned about the impact of the goserelin in combination with chemotherapy on premenopausal breast cancer, in order to improve the quality of research. It is recommended that future studies avoid low-level repetition, and comply with the standards of randomized double-blind test with multi-center and large sample to design experiments; the reports about clinical trials of negative results should be emphasized; it is expected to obtain more reliable conclusions drawn for clinical applications. References Ai Z, Ning X, Shou T, Tang W, Luo Y, Zhang J. Association of interleukin-6 promoter polymorphism with knee osteo- arthritis: A meta-analysis. Chin Med J (Engl). 2014; 127: 2492- 96. Baum M, Hackshaw A, Houghton J, Rutqvist, Fornander T, Nordenskjold B, Nicolucci A, Sainsbury R. Adjuvant gose- relin in pre-menopausal patients with early breast cancer: Results from the ZIPP study. Eur J Cancer. 2006; 42: 895-904. 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Author Info Principal Contact Zhe Xu e-mail: Zhexupzc@163.com First two authors contributed equally 996 Bangladesh J Pharmacol 2015; 10: 988-996 Your feedback about this paper 1. Number of times you have read this paper 2. Quality of paper 3. Your comments Excellent Good Moderate Not good Materials and Methods: Results: References: Conclusion: Text1: Group2: Off Dropdown3: [0] DatePrinted: This article was downloaded by you on: Sep 14, 2016