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Analysis Of Prognostic Factors On Survival In Patients With T Riple-negative Breast Cancer And Prognostic Impact Of BRC A1, Topo Ⅱα, Bcl-2in Breast Cancer

Posted on:2013-01-07Degree:MasterType:Thesis
Country:ChinaCandidate:J MaFull Text:PDF
GTID:2214330374959242Subject:Oncology
Abstract/Summary:PDF Full Text Request
Objective: Triple-negative breast cancer (TNBC), defined as tumorsthat do not express estrogen receptor(ER), progesterone receptor (PR),and HER-2genes in immunohistochemisty. Triple-negative breast cancersaccount for approximately10%–17%of all breast cancers, and characterized by strong in invasive, early in recurrence and fast in progress. Anumber of studies have been reported at home and abroad that, many factors can impact the prognosis of TNBC, such as tumor size, lymph node status, clinical stage, pathology type and so on.30%of women with TNBC were BRCA1mutation carriers, and TNBC account for90%among breast cancer with a BRCA1mutation. There are many similarities in Phenotype feature and molecular level between TNBC and BRCA1mutational breast cancer. Topoisomerase Ⅱ α(TopoⅡ α) is a prolease closely related to DNA duplicate and repair in a eukaryotic cell. Many studies have shown that, Topo Ⅱ αexpression can impact the prognosis of breast cancer. Bcl-2is an anti-apoptotic gene, recent studies have shownthat the expression of Bcl-2was associated with mortality and recurrentrisk in TNBC. This study will analyze the prognostic factors on survival in patients with TNBC, and explore the expression of BRCA1, TopoⅡα,Bcl-2in breast cancer, evaluate its impact on the prognosis of breast cancer, in order to provide some reference for clinicians to choosemore scientific, rational, individualized treatment programs.Method:1The data of501cases of TNBC patients who had received surgery treatment, female, with complete follow-up in the Fourth Hospital of Hebei Medical University from January2005to December2010was collected. All the cases were confirmed negative for ER, PR and Her-2by histopathological examination. The clinicopathologic data including age, menopausal status, family history, histological type, histological grade, lymphovascular invasion, P53status, Ki-67status, tumor size, lymphnode status, clinical stage, whether adjuvant chemotherapy and radiotherapy, etc, and a Excel database was established. All the patients were followed-up by telephone. In the study the first day after surgery is defined as the starting point, and patient death, lost follow-up or last follow-up as the ending of the study, death due to breast cancer as the studyoutcome. During the study period, the patients who died of other causes,lost or still alive when the last time of follow-up were counted as censored data. The follow-up deadline was October31,2011. Prognosis related follow-up include: whether alive, whether local recurrence or distant metastasis, recurrence or metastasis of time, general conditions. The overall survival time was defined as prognostic indicator, retrospective analyzed the clinical and pathological features of TNBC and prognostic factors. SPSS13.0statistical software was used for statistical analysis, withP<0.05as the significance test level. Kaplan-Meier method was used to estimate survival, univariate analysis using Kaplan-Meier method, Log-Rank test was used to compare survival rate, Cox proportional hazardsmodel was used to multivariate analysis.252cases of breast cancer patients′tissue microarrays and clinicopathologic data which had surgical treatment in the Fourth Hospital of Hebei Medical University from January2005to December2006were collected, in which TNBC and non-TNBC were26cases respectively, allof them were female, not receiving preoperative radiotherapy, chemotherapy and other treatments. All the tissue microarrays were cut into4umthick serial sections, the expression of BRCA1, Bcl-2, TopoⅡ α proteinwere detected using immunohistochemical method. SPSS13.0statistical software was used for statistical analysis, chi-squared test for the numeration data, Kaplan-Meier method for survival analysis, Log-Rank test to compare survival rate.Results:1The mean age of the501analyzed TNBC patients (aged23-80years) was51years old. From the first day after operation to October31,2011, the follow-up time was10-81months, with a median follow-up time of29months, of all the501patients, died104cases (20.8%),lost follow-up41cases (8.18%), recurrence and metastasis in117cases (23.4%), and the1,3,5year overall survival rates were:96.2%,78.6%,64.9%, respectively.2Univariate analysis showed that Ki-67, lymph node status, tumorsize, clinical stage, lymphovascular invasion can impact on overall survival in TNBC patients (P <0.05). Cox multivariate analysis showed thatlymph node status and tumor size were independent factors affecting overall survival in TNBC.3In the52cases of breast cancer selected, there are12cases were died,21cases had local recurrence or distant metastasis, BRCA1positive appeared in31patients and negative in21cases; TopoⅡ αpositiveshowed in23cases, negative in29cases; Bcl-2positive and negativewere28and24respectively. Kaplan-Meier method was applied to compared the5-year overall survival and disease-free survival rate in patients with various indicators of positive and negative, the results showed: BRCA1, TopoⅡ α,Bcl-2positive patients had higher5-year overall survival and disease-free survival rate than negative ones, the differences werestatistically significant (P <0.05).4In the26cases of TNBC patients, BRCA1positive appeared in9cases and negative in17cases; Topo Ⅱα positive showed in9casesand negative in17cases; Bcl-2positive and negative were13cases respectively. And in the26cases of non-TNBC patients, BRCA1positiveappeared in22cases, negative in4cases; TopoⅡ α positive in14cases,negative12cases; Bcl-2positive in15cases, negative in11cases.χ2test was used to compare the various indicators′difference of positive r ate between TNBC and non-TNBC group. The results showed: BRCA1positive rate was significantly lower in TNBC than non-TNBC group, the difference was statistically significant (P=0.000). For TopoⅡ αand Bcl-2, there were no significant difference of positive rate in TNBC andnon-TNBC group (P>0.05).Conclusion:1Cox multivariate analysis showed that, the lymph node status andtumor size were independent prognostic factor affecting TNBC.2Low expressions of BRCA1, TopoⅡ αand Bcl-2were correlatedwith the poor prognostic of breast cancer, in which low expression ofBRCA1is closely related with poor prognosis of TNBC.
Keywords/Search Tags:triple-negative breast cancer, prognosis, BRCA1, TopoⅡα, Bcl-2
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