Effect of BRCA1 and BRCA2 mutations on endometrial carcinoma survival rates

Effect of BRCA1 and BRCA2 mutations on endometrial carcinoma survival rates | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research article Effect of BRCA1 and BRCA2 mutations on endometrial carcinoma survival rates Aifen Wang, Robert W Holloway, Zihan Zhao, Ziyue Zhang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-24271/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: To evaluate Effect of BRCA1 and BRCA2 mutations on endometrial carcinoma survival rates. Methods : Data were collected from The Cancer Genome Atlas endometrial cancer database for pathogenic mutations in BRCA1 (58) and BRCA2 (77), coexisting BRCA1 /2 mutations (40), and non-mutations (461). Clinicopathological features and survival rates were compared. Survival time was analyzed using combined data and Cox proportional hazard models, with BRCA1 and BRCA2 as time-varying covariates. Results: Patients with BRCA1 mutations presented with higher risk disease (endometrioid endometrial carcinoma grade 3 and uterine serous carcinoma) than non-carriers and BRCA2 mutation carriers ( p = 0.005 non carriers vs BRCA1 mutation carriers, p = 0.008 BRCA1 mutation carriers vs BRCA2 mutation carriers). BRCA1 and BRCA2 mutation carriers tended to have more endometrioid endometrial carcinoma grade 3 than non-carrier group. Overall survival (OS) rates were higher for all patients with BRCA1 and BRCA2 mutations than non-carriers. Patients with BRCA2 mutations had the most favorable progression-free survival (PFS), followed by patients with BRCA1 and BRCA2 co-mutations, and then BRCA1 alteration carriers ( p = 0.011). BRCA1/2 non-carriers had the worst PFS and OS. Conclusions: Patients with BRCA1 mutations presented with higher risk disease than non-carriers and BRCA2 mutation carriers. BRCA1 and BRCA2 mutation carriers had more favorable OS and PFS than non- BRCA mutation carriers in patients with endometrioid endometrial carcinoma and uterine serous carcinoma. Cancer Biology Oncology Endometrial carcinoma BRCA1 BRCA2 prognosis Figures Figure 1 Figure 2 Background Endometrial cancer is the most common gynecologic malignancy in advanced countries [1]. The incidence of endometrial cancer increased 0.7% per year from 1999 to 2015, according to data from the National Cancer Institute’s Surveillance, Epidemiology and End Results program. The mortality of endometrial cancer grew 1% per year from 1999 to 2015, based on analyses from the Centers for Disease Control and Prevention [2]. Two types of endometrial cancer are classified by clinicohistological features and genetic characteristics. Type 1 endometrial carcinoma is associated with hyperestrogenism and favorable prognosis [3, 4]. Histologic features of the cancer tissue are more likely to present endometrial gland-like carcinoma. Genetic features are related to PTEN and POLE [5, 6]. Type 2 endometrial carcinoma is more aggressive than type 1 and is more likely to be associated with BRCA1 , BRCA2 and TP53 [5, 6]. Clear cell, serous carcinoma, and mixed carcinoma are classified as type 2 endometrial carcinomas. Germline BRCA1 and BRCA2 are well-known risk factors of both ovarian and breast cancer and are identified in 6-15% of females with epithelial ovarian carcinoma [7-9]. A multinational cohort study of patients with 11,847 BRCA1 mutations revealed a distinct increased risk of uterine carcinoma (HR 2.65, 95% CI 1.69-4.16) [10]. However, a prospective study found that the significantly increased risk was associated with BRCA1/2 deficiencies in patients taking tamoxifen [11]. Some data identified an increased risk of uterine serous carcinoma in patients with BRCA mutations [12-14]. BRCA1/2 mutations are related to homologous recombination, DNA repair, chromatin remodeling, cell cycle checkpoint surveillance, and transcriptional regulation [15]. The clinicopathological features of BRCA1/2 mutations carriers differ from features of non-carriers in epithelial ovarian cancer. Patients with BRCA1 mutations tend to have more aggressive histology [15], higher grade [16], and more advanced stage than non-carriers [16, 17]. Less data was available in BRCA2 mutated epithelial ovarian cancers and uterine serous carcinomas due to lower prevalence [15, 17, 18]. One small cohort identified that prognosis was similar in BRCA mutated uterine serous carcinoma and non-carriers [17]. Another study found that g BRCA1 and g BRCA2 mutation carriers were associated with favorable 5-year overall survival in epithelial ovarian cancer [19]. Some studies revealed that BRCA1 and BRCA2 mutation carriers had better prognosis than non-carriers [16, 18, 20], whereas others failed to find differences [21, 22]. One study reported that BRCA2 mutation carriers have more favorable outcomes than non-carriers [23]. Less data is available for prognosis of patients with endometrial carcinomas based on BRCA1 and BRCA2 mutations status [17]. The mechanism of impact of BRCA1/2 mutations on prognosis of cancers is unclear. The literature hypothesizes that favorable prognosis of patients with BRCA1/2 mutations may be caused by good response to platinum-based chemotherapy regimens [18, 24]. This hypothesis is consistent with vitro studies that demonstrated that BRCA1 and BRCA2 mutated cells have a good response to agents, such as platinum-based regimens that induce double-strand DNA breaks [25]. From The Cancer Genome Atlas (TCGA) dataset, we aimed to obtain evidence of the effect of BRCA mutations on prognosis of endometrioid endometrial carcinoma and uterine serous carcinoma. Since limited data are available for patients with endometrial cancer with BRCA1 and BRCA2 mutations, these results may provide evidence on the biology of BRCA1/2 mutations, the clinical management of mutation carriers, and the potential impact of clinical trial designs, especially regimens targeting BRCA1/2 mutations, such as poly (ADP-ribose)-polymerase (PARP) inhibitors [26]. Methods Study Design The data was obtained from The Cancer Genome Atlas endometrial cancer database (provisional and Pancancer Atlas), which involved 27 U.S. institutions between 1988 and 2014, and was used for this study because of its large sample size and user-friendly data structure [http://www.cbioportal.org]. All study participants had been diagnosed as endometrial carcinoma. The retrospective cohort was generated from 529 patients from the Pancancer Atlas database and 548 patients from the provisional database. After excluding duplicate patients from both databases (n = 441), the final cohort comprised 636 patients. Somatic and germline BRCA1 and BRCA2 mutations were not separated. We obtained clinical, demographic, molecular, and pathology information from these patients. Patients were stratified into four groups according to BRCA1 and BRCA2 mutation status: BRCA1 mutation, BRCA2 mutation, coexisting BRCA1 and BRCA2 mutation, and non-carriers. Variables recorded for each case were as follows: histology (endometroid endometrial carcinoma and uterine serous carcinoma included), age at diagnosis (70, 50-69, <50 years old), mean age at diagnosis, myometrial invasion (50% or <50% myometrial invasion), lymph node involvement, and International Federation of Gynecology and Obstetrics (FIGO) stage (2009 version). Overall survival (OS) was defined as the interval from the date of initial surgical resection to the date of death or last contact. Progression-free survival (PFS) was defined as the interval from the date of diagnosis or surgical resection to the date of recurrence, death, or censored last contact. Statistical Analysis Statistical analysis was performed using Mann-Whitney tests for continuous variables, and chi-square analysis and Fisher’s exact test for categorical variables. The Student’s t-test was used to analyze body mass index and age of onset. OS and PFS were analyzed using the Kaplan-Meier method and the log-rank tests starting at the date of diagnosis. Analyses of risk factors were performed using multivariate Cox proportional hazards models. For all tests, statistical significance was less than 0.05 (p < 0.05, exact 2-tailed). All calculations were performed using SPSS software (Version 23, IBM, USA). Results The study included 636 endometrial cancer cases with pathogenic mutations in BRCA1 (58), BRCA2 (77), both BRCA1 and BRCA2 (40), and non-carriers (461). Data were available on 100% for age of onset, 83% for body mass index, 100% for tumor stage, 100% for myometrial invasion, 97% for lymph node involvement, 95.5% for overall survival and 93.1% for progression-free interval. Each patient received appropriate therapy by current National Comprehensive Cancer Network (NCCN) guideline. Patients with BRCA1 mutations presented with higher risk disease (endometrioid grade 3 endometrial carcinoma and uterine serous carcinoma) than non-carrier group and BRCA2 mutation carriers ( p = 0.005, non-carrier group vs BRCA1 mutation carriers; p = 0.008, BRCA1 mutation carriers vs BRCA2 mutation carriers). More patients with BRCA1 and BRCA2 mutation occurred in grade 3 endometrioid endometrial carcinomas than non-carrier group. There were fewer patients with BRCA2 and BRCA1 mutation than non-carrier group in uterine serous carcinomas (Table 1). BRCA1 mutations and BRCA2 mutations carriers were associated with having a younger age at the time of diagnosis than noncarriers ( p = 0.036, BRCA1 mutation carriers vs non carriers; p = 0.001, BRCA2 mutation carriers vs non carriers). Compared to patients with BRCA1 mutations, body mass index was higher in non-carriers. No significant differences were identified between BRCA1 and BRCA2 mutation carriers for mean age at diagnosis ( p = 0.559). We failed to detect any differences in body mass index between BRCA2 mutation carriers and BRCA non-carriers ( p = 0.120), and between BRCA1 carriers and BRCA2 carriers ( p = 0.148). No significant differences were found in depth for myometrial invasion or lymph node involvement among BRCA1 mutation, BRCA2 mutation, and BRCA1/2 mutation carriers ( p > 0.05, Table 1). There were no differences identified in stage among BRCA mutated carriers and non-carriers ( p > 0.05, Table 1). This study did not include patients with coexisting BRCA1 and BRCA2 mutations because of the limited number of cases. Table 1 Clinicopathologic characteristics of endometrial carcinoma based on BRCA mutation status. a, b Variable Noncarrier group (n = 461) BRCA1 mutation carriers (n = 58) BRCA2 mutation carriers (n = 77) P 1 P 2 P 3 Histology EEC G1 76/461 (16.5) 5/58 (8.6) 13/77 (16.9) 0.129 0.063 0.99 0.885 0.003 0.002 0.205 0.173 0.603 0.074 EEC G2 107/461 (23.2) 7/58 (12.1) 17/77 (22.1) EEC G3 139/461 (30.1) 31/58 (53.4) 37/77 (48.1) USC 139/461 (30.1) 15/58 (25.9) 10/77 (12.9) High risk c 278/461 (60.3) 46/58 (79.3) 47/77 (61.0) 0.005 >0.99 0.008 Age Mean ± SD 64.4 ± 10.7 61.1 ± 12.7 59.9 ± 12.0 0.036 0.001 0.559 >70 y 145/460 (31.5) 11/56 (19.6) 13/75 (17.3) 50-70 y 279/460 (60.7) 37/56 (66.1) 52/75 (69.3) <50 y 36/460 (7.8) 8/56 (14.3) 10/75 (13.3) Missing 1/461 (0.2) 2/58 (3.4) 2/77 (1.3) Myometrial invasion =50% 205/452 (45.4) 29/58 (50.0) 31/75 (41.3) Missing 9/461 (2.0) 0 2/77 (1.3) Lymph node invasion Positive 69/397 (17.4) 9/49 (18.4) 11/71 (15.4) 1.000 0.847 0.704 Negative 328/397 (82.6) 40/49 (81.7) 60/71 (84.5) No LND (stage II) 20/461 (4.3) 4/58 (6.9) 1/77 (1.3) BMI Mean ± SD 34.3 ± 17.4 29.8 ± 7.6 31.2 ± 8.7 0.034 0.120 0.148 30 264/433 (61.0) 26/55 (47.3) 35/73 (50.0) Missing 28/461 (6.1) 3/58 (5.6) 4/77 (6.5) FIGO stage I-II 327/461 (70.9) 39/58 (67.2) 59/77 (76.6) 0.647 0.420 0.156 III-IV 134/461 (29.1) 19/58 (32.8) 18/77 (23.4) Abbreviations: EEC, endometrioid endometrial carcinoma; USC, uterine serous carcinoma; LND, lymphadenectomy P 1 , non-carriers VS BRCA1 carriers; P 2 , non-carriers VS BRCA2 carriers; P 3 , BRCA1 carriers VS BRCA2 carriers a Values are given as mean ± SD or number/number (percentage) unless indicated otherwise. b Only available data included, denominators represent patients with available information. e Endometroid endometrial carcinoma and uterine serous carcinoma. Patients with BRCA1 and/or BRCA2 mutation had more favorable OS (p < 0.001, Figure 1) and PFS ( p = 0.008, Figure 2) than non-carriers (Table 2). Patients with BRCA2 mutations had the longest PFS, followed by patients with BRCA1/2 mutations, and then BRCA1 mutations. BRCA1/2 non-carriers had the worst PFS. Table 2 Comparison of PFS and OS of patients based on BRCA mutation status Variable PFS (months) Mean ± SD (95% CI) p OS (months) Mean ± SD (95% CI) p Noncarriers 102.8 ± 3.8 (95.3-110.3) 0.011 121.9 ± 8.6 (105.1-138.8) <0.001 BRCA1 mutation 191.2 ± 12.3 (167.2-215.3) 189.9 ± 21.0 (148.9-231.0) BRCA2 mutation 207.5 ± 6.9 (194.1-221.0) 180.1 ± 31.6 (118.3-242.0) BRCA1/2 mutation 202.3 ± 10.8 (181.1-223.4) 176.0 ± 31.2 (114.8-237.1) Abbreviations: PFS, progression free survival; OS, overall survival Independent factors associated with better prognosis in all endometrial adenocarcinomas were BRCA1/2 mutation, <50% myometrial invasion, and lymph node-negative status (Table 3). Compared to noncarriers, the hazard ratio was 0.29 (95% CI, 0.10-0.78; p = 0.015) for carriers of BRCA1 , 0.17 (95% CI, 0.05-0.54; p = 0.003) for BRCA2, and 0.29 (95% CI, 0.05-0.59; p = 0.037) for BRCA1/2 . We noticed a significant increased risk in ³ 50% myometrial invasion (HR, 2.87; 95% CI, 1.65-5.00; p < 0.001). Compared to lymph node-positive status, the hazard ratio of lymph node negative was 0.18 (95% CI, 0.05-0.59; p = 0.005). Table 3 Relative risk of overall survival (OS) and progression-free interval (PFS) in patients with endometrial carcinoma in relation to histology and grade (Multivariate Cox proportional hazards model). All patients ( N = 565) OS (414/565) PFS (396/565) Variable name HR [95% CI] P HR [95% CI] P Myometrial invasion ³ 50% vs. <50% 2.87 [1.65–5.00] <0.001 2.60 [1.23–5.38] 0.010 BRCA1/2 mutation vs. BRCA noncarriers 0.29 [0.09–0.93] 0.037 N/A N/A BRCA1 mutation vs. BRCA noncarriers 0.29 [0.10–0.78] 0.015 N/A N/A BRCA2 mutation vs. BRCA noncarriers 0.17 [0.05–0.54] 0.003 N/A N/A Lymph node – vs. lymph node + 0.18 [0.05–0.60] 0.005 N/A N/A Discussion To the best of our knowledge, this study was the first to investigate the effect of BRCA mutations on the prognosis of endometrioid endometrial carcinoma. Patients with BRCA1 mutations presented with higher risk disease than non-carrier group and BRCA2 mutation carriers [17]. Among endometrioid endometrial carcinoma group, there were more patients with BRCA1 or BRCA2 mutation than non-carrier group in our study. Patients with BRCA1 and BRCA2 mutations had more favorable outcomes than noncarriers in endometrial carcinoma, which differ from the results of previous studies. There were no significant differences identified in prognosis of uterine serous carcinoma between BRCA mutation carriers and noncarriers [17]. In addition, our findings differ from the analysis of ovarian cancer data from the Cancer Genome Atlas project, and another study that found that patients with BRCA2 mutation had more favorable prognosis than BRCA2 non-carriers [19, 23]. The survival advantage of patients with BRCA1/2 could be associated with intrinsic biological differences, response to therapeutic regimes, or both. The hazard ratios (HR) compared to non-carriers were 0.29 for BRCA1 mutation carriers, 0.17 for BRCA2 mutation carriers, and 0.29 for BRCA1/2 mutation carriers. These findings differ from the hazard ratios for BRCA1 carriers compared to non-carriers reported by Yang et al. (multivariate adjusted HR= 0.76) and other analysis (multivariate adjusted HR= 0.73) among patients with ovarian cancer [19, 23]. The reason for these differences could be that we did not separate germline and somatic BRCA mutations in this study. The survival differences between BRCA2 mutation carriers and non-carriers are attenuated and may even be reversed for BRCA1 mutation carriers in the long run [27, 28]. We presume that resistance to platinum-based treatment was more likely to occur in endometrial carcinoma with BRCA2 mutations than with BRCA1 mutations, leading to reverse prognosis. The mechanism of resistance to platinum-based treatment in BRCA1 and BRCA2 carriers was associated with homologous recombination restoration that occurs by inactivation of the p53-binding protein1 (53BP1), which is important in maintaining the balance between homologous recombination and non-homologous end joining, and is transferred to non-homologous end joining in BRCA1 -mutant cells [29]. One study reported that BRCA1 /2 mutations are associated with favorable prognosis in short-term surveillance, but this advantage attenuates over time, and homologous recombination was reversed through induction by platinum-based treatment in BRCA1 carriers [27]. Newer agents, especially those effective in BRCA1/2 mutation carriers, like PARP inhibitors, are required for treatment of both primary and relapsed cancers with BRCA1/2 mutations and should be investigated in clinical trials for analysis of long-term survival. We saw no differences in lymph node involvement among BRCA1- or BRCA2 -mutated tumors and non-carriers in this study. These results differed from ovarian cancer, in which significant differences were found between patients with BRCA mutations and non-carriers; however, BRCA1- and BRCA2 -related tumors were similar to each other [19]. Our findings contrast with results of breast cancer, in which substantial differences were revealed between BRCA1- and BRCA2 -associated disease [30, 31]. We noticed higher grade histology in endometrial cancers with BRCA1 and BRCA2 alterations, which is similar to the result of ovarian cancer [15, 16]. Our results revealed that fewer BRCA2 and BRCA1 mutations occurred in uterine serous carcinomas than non-carrier group. BRCA1 mutations occurred more frequently than non-mutations in higher risk disease (endometroid endometrial carcinomas and uterine serous carcinomas). Some data showed an increased risk of uterine serous carcinoma in patients with BRCA mutation [12-14]. BRCA1 carriers and non-carriers presented no significant differences in advanced disease in our study, which is similar to the result of previous studies [17]. However, less data is available for BRCA2- mutated epithelial ovarian cancer or endometrial carcinoma due to a lower prevalence [15, 18]. Data showed that women with BRCA mutated recurrent or advanced ovarian cancer responded to olaparib if they failed multiple prior lines of chemotherapy [32, 33]. PARP inhibitors, such as niraparib, rucaparib, and olaparib, are Food and Drug Administration-approved anti-cancer drugs administered after failure of two or three prior lines of treatment in patients with BRCA -mutated recurrent ovarian cancer. For now, there are no clinical trials available for endometrial carcinoma with BRCA mutations using PARP inhibitors. The findings of our study may suggest potential management of patients with BRCA -mutated endometrial carcinoma. Patients could receive individual management if they were stratified based on BRCA mutation status. In addition, our study revealed that BRCA1 - and/or BRCA2 -mutated endometrial carcinomas had better prognosis than non-carriers, even in high-grade or advanced-stage disease. In the future, our findings could be used for counseling patients on their prognosis. This study had several limitations, including its retrospective nature and small sample size. Some clinical information, such as family history, was missing. Further studies are necessary to identify differences between prognosis of endometrial carcinomas and germline or somatic BRCA mutations in larger cohorts. Conclusions Patients with BRCA1 mutations presented with higher risk endometrial carcinoma than non-carrier group or BRCA2 mutation carriers. BRCA1 or BRCA2 mutation carriers tended to have more grade 3 endometrioid endometrial carcinoma than non-carrier group. BRCA1 and BRCA2 mutation carriers have more favorable overall survival and progression-free survival among patients with endometrial carcinoma. Independent factors associated with more favorable prognosis for all endometrial adenocarcinomas included BRCA1/2 mutation, <50% myometrial invasion, and negative lymph node status. Abbreviations FIGO : International Federation of Gynecology and Obstetrics OS : Overall survival PFS : Progression-free survival PARP : poly (ADP-ribose)-polymerase TCGA : The Cancer Genome Atlas Declatations Authors contributions AW analyzed and interpreted the data and was a major contributor in writing the manuscript; AW and RH interpreted the data; ZZ and ZZ abstracted the data; AW designed the work; AW designed the work and interpreted the data. All authors read and approved the final manuscript. Acknowledgement We thank International Science Editing (http://www.internationalscienceediting.com) for editing this manuscript. Ethics approval and consent to participate The study was approved by the Ethics Committee of Zhangjiagang Hospital TCM Affiliated to Nanjing University of Chinese Medicine (committee’s reference number: 2018-1071). Because all patients involved in TCGA were publicly published. The Ethics Committee approved this consent procedure. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-24271","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research article","associatedPublications":[],"authors":[{"id":510172,"identity":"37d72380-5073-411f-9ad7-7a1145dc185c","order_by":1,"name":"Aifen Wang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA00lEQVRIiWNgGAWjYDACZsYHDAwVDMwQHhtRWpgNGBjOkKSFAaiFsQ3GIUYLfzsz4+PCeXfYDY6fTmD4UHaYgX92A34tEoeZmY1nbnvGbHAmdwPjjHOHGSTuHCBgzWH+Y9K82w4zG9zg3cDM23aYwUAiAb8O+cPM7L9550C1/CVGi8FhZjZm3gaoFkZitBgC/SLNc+wwsyTQLwd7zqXzSNwgoEXu/GHGzzw1h5P5jp/d+OBHmbUc/wwCWmAgGUQcAGIe4tQDgR3RKkfBKBgFo2DkAQBjkz6/TE6U7AAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0002-1868-1890","institution":"Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Aifen","middleName":"","lastName":"Wang","suffix":""},{"id":510173,"identity":"54a88898-55af-45df-87ed-89d5bc28fcc5","order_by":2,"name":"Robert W Holloway","email":"","orcid":"","institution":"Florida Hospital Orlando","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Robert","middleName":"W","lastName":"Holloway","suffix":""},{"id":510174,"identity":"6eed7cc5-3691-467f-97a8-0aa00e16e5c7","order_by":3,"name":"Zihan Zhao","email":"","orcid":"","institution":"University of California Santa Barbara","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Zihan","middleName":"","lastName":"Zhao","suffix":""},{"id":510175,"identity":"ac082cca-fc08-4cc5-bcf5-884740e114ca","order_by":4,"name":"Ziyue Zhang","email":"","orcid":"","institution":"University of California San Diego","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ziyue","middleName":"","lastName":"Zhang","suffix":""}],"badges":[],"createdAt":"2020-04-21 16:39:04","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-24271/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-24271/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":986085,"identity":"0d59a10b-acde-4c4d-b43f-48155bff67b5","added_by":"auto","created_at":"2020-04-28 13:42:21","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":145016,"visible":true,"origin":"","legend":"Overall survival from endometrial carcinoma based on BRCA mutation status\nLegend: Overall survival (OS) rates were higher for all patients with BRCA1 or BRCA2 mutations than non-carriers.","description":"","filename":"BRCAnewoverallsurvival.jpg","url":"https://assets-eu.researchsquare.com/files/rs-24271/v1/BRCAnewoverallsurvival.jpg"},{"id":986086,"identity":"fbc2a85a-1873-4d60-b892-75dda20dc03b","added_by":"auto","created_at":"2020-04-28 13:42:21","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":152822,"visible":true,"origin":"","legend":"Progression-free survival from endometrial carcinoma based on BRCA mutation status\nLegend: Patients with BRCA2 mutations had the most favorable progression-free survival (PFS), followed by patients with BRCA1 and BRCA2 co-mutations and BRCA1 alteration carriers. BRCA1/2 non-carriers had the worst PFS.","description":"","filename":"BRCAnewprogressionfreesurvival.jpg","url":"https://assets-eu.researchsquare.com/files/rs-24271/v1/BRCAnewprogressionfreesurvival.jpg"},{"id":13500259,"identity":"38fa43ed-8273-4f38-b4ff-18fca0ef8bb4","added_by":"auto","created_at":"2021-09-16 23:05:40","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":529381,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-24271/v1/65db0319-3af6-4224-aa78-a97b0cd42cee.pdf"}],"financialInterests":"","formattedTitle":"Effect of BRCA1 and BRCA2 mutations on endometrial carcinoma survival rates","fulltext":[{"header":"Background ","content":"\u003cp\u003eEndometrial cancer is the most common gynecologic malignancy in advanced countries [1]. The incidence of endometrial cancer increased 0.7% per year from 1999 to 2015, according to data from the National Cancer Institute\u0026rsquo;s Surveillance, Epidemiology and End Results program. The mortality of endometrial cancer grew 1% per year from 1999 to 2015, based on analyses from the Centers for Disease Control and Prevention [2]. Two types of endometrial cancer are classified by clinicohistological features and genetic characteristics. Type 1 endometrial carcinoma is associated with hyperestrogenism and favorable prognosis [3, 4]. Histologic features of the cancer tissue are more likely to present endometrial gland-like carcinoma. Genetic features are related to \u003cem\u003ePTEN\u003c/em\u003e and \u003cem\u003ePOLE \u003c/em\u003e[5, 6]. Type 2 endometrial carcinoma is more aggressive than type 1 and is more likely to be associated with \u003cem\u003eBRCA1\u003c/em\u003e,\u003cem\u003e BRCA2\u003c/em\u003e and \u003cem\u003eTP53 \u003c/em\u003e[5, 6]. Clear cell, serous carcinoma, and mixed carcinoma are classified as type 2 endometrial carcinomas. Germline \u003cem\u003eBRCA1\u003c/em\u003e and \u003cem\u003eBRCA2\u003c/em\u003e are well-known risk factors of both ovarian and breast cancer and are identified in 6-15% of females with epithelial ovarian carcinoma [7-9]. A multinational cohort study of patients with 11,847 \u003cem\u003eBRCA1\u003c/em\u003e mutations revealed a distinct increased risk of uterine carcinoma (HR 2.65, 95% CI 1.69-4.16) [10]. However, a prospective study found that the significantly increased risk was associated with \u003cem\u003eBRCA1/2\u003c/em\u003e deficiencies in patients taking tamoxifen [11].\u0026nbsp; Some data identified an increased risk of uterine serous carcinoma in patients with \u003cem\u003eBRCA\u003c/em\u003e mutations [12-14]. \u003cem\u003eBRCA1/2\u003c/em\u003e mutations are related to homologous recombination, DNA repair, chromatin remodeling, cell cycle checkpoint surveillance, and transcriptional regulation [15]. The clinicopathological features of \u003cem\u003eBRCA1/2 \u003c/em\u003emutations carriers differ from features of non-carriers in epithelial ovarian cancer. Patients with \u003cem\u003eBRCA1\u003c/em\u003e mutations tend to have more aggressive histology [15], higher grade [16], and more advanced stage than non-carriers [16, 17]. Less data was available in \u003cem\u003eBRCA2 \u003c/em\u003emutated epithelial ovarian cancers and uterine serous carcinomas due to lower prevalence [15, 17, 18]. One small cohort identified that prognosis was similar in \u003cem\u003eBRCA\u003c/em\u003e mutated uterine serous carcinoma and non-carriers [17]. Another study found that g\u003cem\u003eBRCA1\u003c/em\u003e and g\u003cem\u003eBRCA2\u003c/em\u003e mutation carriers were associated with favorable 5-year overall survival in epithelial ovarian cancer [19]. Some studies revealed that \u003cem\u003eBRCA1\u003c/em\u003e and \u003cem\u003eBRCA2\u003c/em\u003e mutation carriers had better prognosis than non-carriers [16, 18, 20], whereas others failed to find differences [21, 22]. One study reported that \u003cem\u003eBRCA2\u003c/em\u003e mutation carriers have more favorable outcomes than non-carriers [23]. Less data is available for prognosis of patients with endometrial carcinomas based on \u003cem\u003eBRCA1\u003c/em\u003e and \u003cem\u003eBRCA2\u003c/em\u003e mutations status [17].\u003c/p\u003e\n\u003cp\u003eThe mechanism of impact of \u003cem\u003eBRCA1/2\u003c/em\u003e mutations on prognosis of cancers is unclear. The literature hypothesizes that favorable prognosis of patients with \u003cem\u003eBRCA1/2\u003c/em\u003e mutations may be caused by good response to platinum-based chemotherapy regimens [18, 24]. This hypothesis is consistent with vitro studies that demonstrated that \u003cem\u003eBRCA1\u003c/em\u003e and \u003cem\u003eBRCA2\u003c/em\u003e mutated cells have a good response to agents, such as platinum-based regimens that induce double-strand DNA breaks [25].\u003c/p\u003e\n\u003cp\u003eFrom The Cancer Genome Atlas (TCGA) dataset, we aimed to obtain evidence of the effect of \u003cem\u003eBRCA \u003c/em\u003emutations on prognosis of endometrioid endometrial carcinoma and uterine serous carcinoma. Since limited data are available for patients with endometrial cancer with \u003cem\u003eBRCA1\u003c/em\u003e and \u003cem\u003eBRCA2 \u003c/em\u003emutations, these results may provide evidence on the biology of \u003cem\u003eBRCA1/2 \u003c/em\u003emutations, the clinical management of mutation carriers, and the potential impact of clinical trial designs, especially regimens targeting \u003cem\u003eBRCA1/2\u003c/em\u003e mutations, such as poly (ADP-ribose)-polymerase (PARP) inhibitors [26].\u003c/p\u003e"},{"header":"Methods","content":"\u003ch2\u003eStudy Design\u003c/h2\u003e\u003cp\u003eThe data was obtained from The Cancer Genome Atlas endometrial cancer database (provisional and Pancancer Atlas), which involved 27 U.S. institutions between 1988 and 2014, and was used for this study because of its large sample size and user-friendly data structure [http://www.cbioportal.org]. All study participants had been diagnosed as endometrial carcinoma. The retrospective cohort was generated from 529 patients from the Pancancer Atlas database and 548 patients from the provisional database. After excluding duplicate patients from both databases (n = 441), the final cohort comprised 636 patients. Somatic and germline BRCA1 and BRCA2 mutations were not separated. We obtained clinical, demographic, molecular, and pathology information from these patients. Patients were stratified into four groups according to BRCA1 and BRCA2 mutation status: BRCA1 mutation, BRCA2 mutation, coexisting BRCA1 and BRCA2 mutation, and non-carriers. Variables recorded for each case were as follows: histology (endometroid endometrial carcinoma and uterine serous carcinoma included), age at diagnosis (70, 50-69, \u0026lt;50 years old), mean age at diagnosis, myometrial invasion (50% or \u0026lt;50% myometrial invasion), lymph node involvement, and International Federation of Gynecology and Obstetrics (FIGO) stage (2009 version). Overall survival (OS) was defined as the interval from the date of initial surgical resection to the date of death or last contact. Progression-free survival (PFS) was defined as the interval from the date of diagnosis or surgical resection to the date of recurrence, death, or censored last contact. \u003c/p\u003e\u003ch2\u003eStatistical Analysis\u003ch2\u003e \u003cp\u003eStatistical analysis was performed using Mann-Whitney tests for continuous variables, and chi-square analysis and Fisher\u0026rsquo;s exact test for categorical variables. The Student\u0026rsquo;s t-test was used to analyze body mass index and age of onset. OS and PFS were analyzed using the Kaplan-Meier method and the log-rank tests starting at the date of diagnosis. Analyses of risk factors were performed using multivariate Cox proportional hazards models. For all tests, statistical significance was less than 0.05 (p \u0026lt; 0.05, exact 2-tailed). All calculations were performed using SPSS software (Version 23, IBM, USA).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThe study included 636 endometrial cancer cases with pathogenic mutations in \u003cem\u003eBRCA1 \u003c/em\u003e(58), \u003cem\u003eBRCA2 \u003c/em\u003e(77), both \u003cem\u003eBRCA1\u003c/em\u003e and \u003cem\u003eBRCA2\u003c/em\u003e (40), and non-carriers (461). Data were available on 100% for age of onset, 83% for body mass index, 100% for tumor stage, 100% for myometrial invasion, 97% for lymph node involvement, 95.5% for overall survival and 93.1% for progression-free interval. Each patient received appropriate therapy by current National Comprehensive Cancer Network (NCCN) guideline. Patients with \u003cem\u003eBRCA1\u003c/em\u003e mutations presented with higher risk disease (endometrioid grade 3 endometrial carcinoma and uterine serous carcinoma) than non-carrier group and \u003cem\u003eBRCA2 \u003c/em\u003emutation carriers (\u003cem\u003ep \u003c/em\u003e= 0.005, non-carrier group vs \u003cem\u003eBRCA1 \u003c/em\u003emutation carriers;\u003cem\u003e p\u003c/em\u003e = 0.008, \u003cem\u003eBRCA1 \u003c/em\u003emutation carriers vs \u003cem\u003eBRCA2 \u003c/em\u003emutation carriers). More patients with \u003cem\u003eBRCA1 \u003c/em\u003eand \u003cem\u003eBRCA2\u003c/em\u003e mutation occurred in grade 3 endometrioid endometrial carcinomas than non-carrier group. There were fewer patients with \u003cem\u003eBRCA2\u003c/em\u003e and \u003cem\u003eBRCA1\u003c/em\u003e mutation than non-carrier group in uterine serous carcinomas (Table 1). \u003cem\u003eBRCA1\u003c/em\u003e mutations and \u003cem\u003eBRCA2\u003c/em\u003e mutations carriers were associated with having a younger age at the time of diagnosis than noncarriers (\u003cem\u003ep\u003c/em\u003e = 0.036,\u003cem\u003e BRCA1\u003c/em\u003e mutation carriers vs non carriers;\u003cem\u003e p\u003c/em\u003e = 0.001,\u003cem\u003e BRCA2\u003c/em\u003e mutation carriers vs non carriers). Compared to patients with \u003cem\u003eBRCA1\u003c/em\u003e mutations, body mass index was higher in non-carriers. No significant differences were identified between \u003cem\u003eBRCA1\u003c/em\u003e and \u003cem\u003eBRCA2\u003c/em\u003e mutation carriers for mean age at diagnosis (\u003cem\u003ep\u003c/em\u003e = 0.559). We failed to detect any differences in body mass index between \u003cem\u003eBRCA2\u003c/em\u003e mutation carriers and \u003cem\u003eBRCA\u003c/em\u003e non-carriers (\u003cem\u003ep\u003c/em\u003e = 0.120), and between \u003cem\u003eBRCA1 \u003c/em\u003ecarriers and \u003cem\u003eBRCA2\u003c/em\u003e carriers (\u003cem\u003ep\u003c/em\u003e = 0.148). No significant differences were found in depth for myometrial invasion or lymph node involvement among \u003cem\u003eBRCA1\u003c/em\u003e mutation, \u003cem\u003eBRCA2\u003c/em\u003e mutation, and \u003cem\u003eBRCA1/2\u003c/em\u003e mutation carriers (\u003cem\u003ep \u003c/em\u003e\u0026gt; 0.05, Table 1). There were no differences identified in stage among \u003cem\u003eBRCA\u003c/em\u003e mutated carriers and non-carriers (\u003cem\u003ep \u003c/em\u003e\u0026gt; 0.05, Table 1). This study did not include patients with coexisting \u003cem\u003eBRCA1\u003c/em\u003e and \u003cem\u003eBRCA2\u003c/em\u003e mutations because of the limited number of cases.\u003c/p\u003e\u003ctable id=\"Tab1\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eClinicopathologic characteristics of endometrial carcinoma based on \u003cem\u003eBRCA\u003c/em\u003e mutation status. \u003csup\u003ea, b\u003c/sup\u003e\u003c/div\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd width=\"102\"\u003e\n\u003cp\u003eVariable\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003eNoncarrier group \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e(n = 461)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e\u003cem\u003eBRCA1 \u003c/em\u003emutation carriers (n = 58)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" width=\"138\"\u003e\n\u003cp\u003e\u003cem\u003eBRCA2 \u003c/em\u003emutation carriers (n = 77)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"72\"\u003e\n\u003cp\u003e\u003cem\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp; P\u003csup\u003e1\u003c/sup\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"60\"\u003e\n\u003cp\u003e\u003cem\u003e\u0026nbsp; P\u003csup\u003e2\u003c/sup\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"84\"\u003e\n\u003cp\u003e\u003cem\u003e\u0026nbsp; P\u003csup\u003e3\u003c/sup\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"102\"\u003e\n\u003cp\u003e\u003cstrong\u003eHistology\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" width=\"102\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"60\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"84\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"102\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp; EEC G1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e76/461 (16.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e5/58 (8.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" width=\"138\"\u003e\n\u003cp\u003e13/77 (16.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"4\" width=\"72\"\u003e\n\u003cp\u003e0.129\u003c/p\u003e\n\u003cp\u003e0.063\u003c/p\u003e\n\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003cp\u003e0.545\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"4\" width=\"60\"\u003e\n\u003cp\u003e\u0026gt;0.99\u003c/p\u003e\n\u003cp\u003e0.885\u003c/p\u003e\n\u003cp\u003e0.003\u003c/p\u003e\n\u003cp\u003e0.002\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"4\" width=\"84\"\u003e\n\u003cp\u003e0.205\u003c/p\u003e\n\u003cp\u003e0.173\u003c/p\u003e\n\u003cp\u003e0.603\u003c/p\u003e\n\u003cp\u003e0.074\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"102\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp; EEC G2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e107/461 (23.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e7/58 (12.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" width=\"138\"\u003e\n\u003cp\u003e17/77 (22.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"102\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp; EEC G3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e139/461 (30.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e31/58 (53.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" width=\"138\"\u003e\n\u003cp\u003e37/77 (48.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"102\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp; USC\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e139/461 (30.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e15/58 (25.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" width=\"138\"\u003e\n\u003cp\u003e10/77 (12.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"102\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp; High risk\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e278/461 (60.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e46/58 (79.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" width=\"138\"\u003e\n\u003cp\u003e47/77 (61.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"72\"\u003e\n\u003cp\u003e0.005\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"60\"\u003e\n\u003cp\u003e\u0026gt;0.99\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"84\"\u003e\n\u003cp\u003e0.008\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"102\"\u003e\n\u003cp\u003e\u003cstrong\u003eAge\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" width=\"102\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"60\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"84\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"102\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp; Mean \u0026plusmn; SD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e64.4 \u0026plusmn; 10.7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e61.1 \u0026plusmn; 12.7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e59.9 \u0026plusmn; 12.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" rowspan=\"5\" width=\"102\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp; \u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;0.036\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; \u0026nbsp;\u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"5\" width=\"60\"\u003e\n\u003cp\u003e0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"5\" width=\"84\"\u003e\n\u003cp\u003e0.559\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"102\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp; \u0026gt;70 y\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e145/460 (31.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e11/56 (19.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e13/75 (17.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"102\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp; 50-70 y\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e279/460 (60.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e37/56 (66.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e52/75 (69.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"102\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp; \u0026lt;50 y\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e36/460 (7.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e8/56 (14.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e10/75 (13.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"102\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp; Missing\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e1/461 (0.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e2/58 (3.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e2/77 (1.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"102\"\u003e\n\u003cp\u003e\u003cstrong\u003eMyometrial invasion\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" width=\"102\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"60\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"84\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"102\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp; \u0026lt;50%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e247/452 (54.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e29/58 (50.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e44/75 (58.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" rowspan=\"2\" width=\"102\"\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;0.571\u0026nbsp;\u0026nbsp;\u0026nbsp; \u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"60\"\u003e\n\u003cp\u003e\u0026nbsp;0.668\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"84\"\u003e\n\u003cp\u003e\u0026nbsp;0.256\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"102\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp; \u0026gt;=50%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e205/452 (45.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e29/58 (50.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e31/75 (41.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"102\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp; Missing\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e9/461 (2.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e2/77 (1.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" width=\"102\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"60\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"84\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"102\"\u003e\n\u003cp\u003e\u003cstrong\u003eLymph node invasion\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" width=\"102\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"60\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"84\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"102\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp; Positive\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e69/397 (17.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e9/49 (18.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e11/71 (15.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" rowspan=\"4\" width=\"102\"\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;1.000\u0026nbsp;\u0026nbsp; \u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"4\" width=\"60\"\u003e\n\u003cp\u003e\u0026nbsp;0.847\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"4\" width=\"84\"\u003e\n\u003cp\u003e\u0026nbsp;0.704\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"102\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp; Negative\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e328/397 (82.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e40/49 (81.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e60/71 (84.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"102\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp; No LND (\u0026lt;=stage II)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e44/461 (9.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e5/58 (8.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e5/77 (6.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"102\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp; No LND (\u0026gt;stage II)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e20/461 (4.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e4/58 (6.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e1/77 (1.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"102\"\u003e\n\u003cp\u003e\u003cstrong\u003eBMI\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" width=\"102\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"60\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"84\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"102\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp; Mean \u0026plusmn; SD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e34.3 \u0026plusmn; 17.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e29.8 \u0026plusmn; 7.6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e31.2 \u0026plusmn; 8.7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" width=\"102\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp; 0.034\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"60\"\u003e\n\u003cp\u003e0.120\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"84\"\u003e\n\u003cp\u003e\u0026nbsp; 0.148\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"102\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp; \u0026lt;25\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e78/433 (18.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e16/55 (29.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e24/73 (32.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" rowspan=\"4\" width=\"102\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"4\" width=\"60\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"4\" width=\"84\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"102\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp; 25-30\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e91/433 (21.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e13/55 (23.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e14/73 (17.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"102\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp; \u0026gt;30\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e264/433 (61.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e26/55 (47.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e35/73 (50.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"102\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp; Missing\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e28/461 (6.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e3/58 (5.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e4/77 (6.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"102\"\u003e\n\u003cp\u003e\u003cstrong\u003eFIGO stage\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" width=\"102\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"60\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"84\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"102\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp; I-II\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e327/461 (70.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e39/58 (67.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e59/77 (76.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" rowspan=\"2\" width=\"102\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; 0.647\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"60\"\u003e\n\u003cp\u003e0.420\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"2\" width=\"84\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp; 0.156\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"102\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp; III-IV\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e134/461 (29.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"126\"\u003e\n\u003cp\u003e19/58 (32.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"108\"\u003e\n\u003cp\u003e18/77 (23.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"8\"\u003e\n\u003cp\u003eAbbreviations: EEC, endometrioid endometrial carcinoma; USC, uterine serous carcinoma; LND, lymphadenectomy\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eP\u003csup\u003e1\u003c/sup\u003e\u003c/em\u003e, non-carriers VS \u003cem\u003eBRCA1 \u003c/em\u003ecarriers; \u003cem\u003eP\u003csup\u003e2\u003c/sup\u003e\u003c/em\u003e, non-carriers VS \u003cem\u003eBRCA2 \u003c/em\u003ecarriers;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eP\u003csup\u003e3\u003c/sup\u003e\u003c/em\u003e, \u003cem\u003eBRCA1\u003c/em\u003e carriers VS \u003cem\u003eBRCA2 \u003c/em\u003ecarriers\u003c/p\u003e\n\u003cp\u003e\u003csup\u003ea \u003c/sup\u003eValues are given as mean \u0026plusmn; SD or number/number (percentage) unless indicated otherwise.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003eb \u003c/sup\u003eOnly available data included, denominators represent patients with\u003c/p\u003e\n\u003cp\u003eavailable information.\u003c/p\u003e\n\u003csup\u003ee \u003c/sup\u003eEndometroid endometrial carcinoma and uterine serous carcinoma.\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003ePatients with \u003cem\u003eBRCA1 \u003c/em\u003eand/or \u003cem\u003eBRCA2 \u003c/em\u003emutation had more favorable OS (p \u0026lt; 0.001, Figure 1) and PFS (\u003cem\u003ep \u003c/em\u003e= 0.008, Figure 2) than non-carriers (Table 2). Patients with \u003cem\u003eBRCA2\u003c/em\u003e mutations had the longest PFS, followed by patients with \u003cem\u003eBRCA1/2\u003c/em\u003e mutations, and then \u003cem\u003eBRCA1 \u003c/em\u003emutations. \u003cem\u003eBRCA1/2\u003c/em\u003e non-carriers had the worst PFS.\u003c/p\u003e\u003ctable id=\"Tab2\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eComparison of PFS and OS of patients based on \u003cem\u003eBRCA\u003c/em\u003e mutation status\u003c/div\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd width=\"132\"\u003e\n\u003cp\u003eVariable\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"186\"\u003e\n\u003cp\u003ePFS (months)\u003c/p\u003e\n\u003cp\u003eMean \u0026plusmn; SD (95% CI)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"54\"\u003e\n\u003cp\u003e\u003cem\u003e\u0026nbsp;\u0026nbsp; p\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"186\"\u003e\n\u003cp\u003eOS (months)\u003c/p\u003e\n\u003cp\u003eMean \u0026plusmn; SD (95% CI)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"60\"\u003e\n\u003cp\u003e\u003cem\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; p\u003c/em\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"132\"\u003e\n\u003cp\u003eNoncarriers\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"186\"\u003e\n\u003cp\u003e102.8 \u0026plusmn; 3.8 (95.3-110.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"4\" width=\"54\"\u003e\n\u003cp\u003e0.011\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"186\"\u003e\n\u003cp\u003e121.9 \u0026plusmn; 8.6 (105.1-138.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd rowspan=\"4\" width=\"60\"\u003e\n\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"132\"\u003e\n\u003cp\u003e\u003cem\u003eBRCA1 \u003c/em\u003emutation\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"186\"\u003e\n\u003cp\u003e191.2 \u0026plusmn; 12.3 (167.2-215.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"186\"\u003e\n\u003cp\u003e189.9 \u0026plusmn; 21.0 (148.9-231.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"132\"\u003e\n\u003cp\u003e\u003cem\u003eBRCA2 \u003c/em\u003emutation\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"186\"\u003e\n\u003cp\u003e207.5 \u0026plusmn; 6.9 (194.1-221.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"186\"\u003e\n\u003cp\u003e180.1 \u0026plusmn; 31.6 (118.3-242.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"132\"\u003e\n\u003cp\u003e\u003cem\u003eBRCA1/2\u003c/em\u003e mutation\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"186\"\u003e\n\u003cp\u003e202.3 \u0026plusmn; 10.8 (181.1-223.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"186\"\u003e\n\u003cp\u003e176.0 \u0026plusmn; 31.2 (114.8-237.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n \u003ctr\u003e\u003ctd colspan=\"5\"\u003eAbbreviations: PFS, progression free survival; OS, overall survival\u003c/td\u003e\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eIndependent factors associated with better prognosis in all endometrial adenocarcinomas were \u003cem\u003eBRCA1/2 \u003c/em\u003emutation, \u0026lt;50% myometrial invasion, and lymph node-negative status (Table 3). Compared to noncarriers, the hazard ratio was 0.29 (95% CI, 0.10-0.78; p = 0.015) for carriers of \u003cem\u003eBRCA1\u003c/em\u003e, 0.17 (95% CI, 0.05-0.54; p = 0.003) for \u003cem\u003eBRCA2,\u003c/em\u003e and 0.29 (95% CI, 0.05-0.59; p = 0.037) for \u003cem\u003eBRCA1/2\u003c/em\u003e. We noticed a significant increased risk in \u0026sup3; 50% myometrial invasion (HR, 2.87; 95% CI, 1.65-5.00; \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001). Compared to lymph node-positive status, the hazard ratio of lymph node negative was 0.18 (95% CI, 0.05-0.59; \u003cem\u003ep\u003c/em\u003e = 0.005).\u003c/p\u003e\u003ctable id=\"Tab3\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cdiv class=\"SimplePara\"\u003eRelative risk of overall survival (OS) and progression-free interval (PFS) in patients with endometrial carcinoma in relation to histology and grade (Multivariate Cox proportional hazards model).\u003c/div\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"2\" rowspan=\"2\" width=\"172\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"4\" width=\"520\"\u003e\n\u003cp\u003eAll patients (\u003cem\u003eN \u003c/em\u003e= 565)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"2\" width=\"236\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; OS (414/565)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" width=\"284\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; PFS (396/565)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"5\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"167\"\u003e\n\u003cp\u003eVariable name\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"151\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; HR [95% CI]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; P\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"202\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; HR [95% CI]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"81\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp; P\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"5\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"167\"\u003e\n\u003cp\u003eMyometrial invasion \u0026sup3; 50% vs. \u0026lt;50%\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"151\"\u003e\n\u003cp\u003e2.87 [1.65\u0026ndash;5.00]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"202\"\u003e\n\u003cp\u003e2.60 [1.23\u0026ndash;5.38]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"81\"\u003e\n\u003cp\u003e0.010\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"5\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"167\"\u003e\n\u003cp\u003e\u003cem\u003eBRCA1/2 \u003c/em\u003emutation vs. \u003cem\u003eBRCA \u003c/em\u003enoncarriers\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"151\"\u003e\n\u003cp\u003e0.29 [0.09\u0026ndash;0.93]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e\u0026nbsp; 0.037\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"202\"\u003e\n\u003cp\u003eN/A\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"81\"\u003e\n\u003cp\u003eN/A\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"5\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"167\"\u003e\n\u003cp\u003e\u003cem\u003eBRCA1 \u003c/em\u003emutation vs. \u003cem\u003eBRCA \u003c/em\u003enoncarriers\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"151\"\u003e\n\u003cp\u003e0.29 [0.10\u0026ndash;0.78]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e\u0026nbsp; 0.015\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"202\"\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp; N/A\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"81\"\u003e\n\u003cp\u003eN/A\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"5\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"167\"\u003e\n\u003cp\u003e\u003cem\u003eBRCA2 \u003c/em\u003emutation vs. \u003cem\u003eBRCA \u003c/em\u003enoncarriers\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"151\"\u003e\n\u003cp\u003e0.17 [0.05\u0026ndash;0.54]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e\u0026nbsp; 0.003\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"202\"\u003e\n\u003cp\u003e\u0026nbsp;N/A\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"81\"\u003e\n\u003cp\u003eN/A\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"5\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"167\"\u003e\n\u003cp\u003eLymph node \u0026ndash; vs. lymph node +\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"151\"\u003e\n\u003cp\u003e0.18 [0.05\u0026ndash;0.60]\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"85\"\u003e\n\u003cp\u003e\u0026nbsp; 0.005\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"202\"\u003e\n\u003cp\u003e\u0026nbsp;N/A\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"81\"\u003e\n\u003cp\u003eN/A\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Discussion","content":"\u003cp\u003eTo the best of our knowledge, this study was the first to investigate the effect of \u003cem\u003eBRCA\u003c/em\u003e mutations on the prognosis of endometrioid endometrial carcinoma. Patients with \u003cem\u003eBRCA1\u003c/em\u003e mutations presented with higher risk disease than non-carrier group and \u003cem\u003eBRCA2 \u003c/em\u003emutation carriers [17]. Among endometrioid endometrial carcinoma group, there were more patients with \u003cem\u003eBRCA1 \u003c/em\u003eor \u003cem\u003eBRCA2\u003c/em\u003e mutation than non-carrier group in our study. Patients with \u003cem\u003eBRCA1 \u003c/em\u003eand \u003cem\u003eBRCA2 \u003c/em\u003emutations had more favorable outcomes than noncarriers in endometrial carcinoma, which differ from the results of previous studies. There were no significant differences identified in prognosis of uterine serous carcinoma between \u003cem\u003eBRCA\u003c/em\u003e mutation carriers and noncarriers [17]. In addition, our findings differ from the analysis of ovarian cancer data from the Cancer Genome Atlas project, and another study that found that patients with\u003cem\u003e BRCA2\u003c/em\u003e mutation had more favorable prognosis than \u003cem\u003eBRCA2 \u003c/em\u003enon-carriers [19, 23]. The survival advantage of patients with \u003cem\u003eBRCA1/2\u003c/em\u003e could be associated with intrinsic biological differences, response to therapeutic regimes, or both. The hazard ratios (HR) compared to non-carriers were 0.29 for \u003cem\u003eBRCA1 \u003c/em\u003emutation carriers, 0.17 for \u003cem\u003eBRCA2\u003c/em\u003e mutation carriers, and 0.29 for \u003cem\u003eBRCA1/2\u003c/em\u003e mutation carriers. These findings differ from the hazard ratios for \u003cem\u003eBRCA1\u003c/em\u003e carriers compared to non-carriers reported by Yang et al. (multivariate adjusted HR= 0.76) and other analysis (multivariate adjusted HR= 0.73) among patients with ovarian cancer [19, 23]. The reason for these differences could be that we did not separate germline and somatic \u003cem\u003eBRCA\u003c/em\u003e mutations in this study. The survival differences between \u003cem\u003eBRCA2\u003c/em\u003e mutation carriers and non-carriers are attenuated and may even be reversed for\u003cem\u003e BRCA1\u003c/em\u003e mutation carriers in the long run [27, 28].\u003c/p\u003e\n\u003cp\u003eWe presume that resistance to platinum-based treatment was more likely to occur in endometrial carcinoma with \u003cem\u003eBRCA2\u003c/em\u003e mutations than with \u003cem\u003eBRCA1 \u003c/em\u003emutations, leading to reverse prognosis. The mechanism of resistance to platinum-based treatment in \u003cem\u003eBRCA1\u003c/em\u003e and \u003cem\u003eBRCA2 \u003c/em\u003ecarriers was associated with homologous recombination restoration that occurs by inactivation of the p53-binding protein1 (53BP1), which is important in maintaining the balance between homologous recombination and non-homologous end joining, and is transferred to non-homologous end joining in \u003cem\u003eBRCA1\u003c/em\u003e-mutant cells [29]. One study reported that \u003cem\u003eBRCA1\u003c/em\u003e/2 mutations are associated with favorable prognosis in short-term surveillance, but this advantage attenuates over time, and homologous recombination was reversed through induction by platinum-based treatment in \u003cem\u003eBRCA1 \u003c/em\u003ecarriers [27]. Newer agents, especially those effective in \u003cem\u003eBRCA1/2 \u003c/em\u003emutation carriers, like PARP inhibitors, are required for treatment of both primary and relapsed cancers with \u003cem\u003eBRCA1/2\u003c/em\u003e mutations and should be investigated in clinical trials for analysis of long-term survival.\u003c/p\u003e\n\u003cp\u003eWe saw no differences in lymph node involvement among \u003cem\u003eBRCA1-\u003c/em\u003e or \u003cem\u003eBRCA2\u003c/em\u003e-mutated tumors and non-carriers in this study. These results differed from ovarian cancer, in which significant differences were found between patients with \u003cem\u003eBRCA\u003c/em\u003e mutations and non-carriers; however, \u003cem\u003eBRCA1-\u003c/em\u003e and \u003cem\u003eBRCA2\u003c/em\u003e-related tumors were similar to each other [19]. Our findings contrast with results of \u0026nbsp;breast cancer, in which substantial differences were revealed between \u003cem\u003eBRCA1-\u003c/em\u003e and \u003cem\u003eBRCA2\u003c/em\u003e-associated disease [30, 31]. We noticed higher grade histology in endometrial cancers with \u003cem\u003eBRCA1\u003c/em\u003e and \u003cem\u003eBRCA2\u003c/em\u003e alterations, which is similar to the result of ovarian cancer [15, 16]. Our results revealed that fewer \u003cem\u003eBRCA2\u003c/em\u003e and\u003cem\u003e BRCA1\u003c/em\u003e mutations occurred in uterine serous carcinomas than non-carrier group. \u003cem\u003eBRCA1\u003c/em\u003e mutations occurred more frequently than non-mutations in higher risk disease (endometroid endometrial carcinomas and uterine serous carcinomas). Some data showed an increased risk of uterine serous carcinoma in patients with \u003cem\u003eBRCA\u003c/em\u003e mutation [12-14]. \u003cem\u003eBRCA1\u003c/em\u003e carriers and non-carriers presented no significant differences in advanced disease in our study, which is similar to the result of previous studies [17]. However, less data is available for \u003cem\u003eBRCA2-\u003c/em\u003emutated epithelial ovarian cancer or endometrial carcinoma due to a lower prevalence [15, 18].\u003c/p\u003e\n\u003cp\u003eData showed that women with \u003cem\u003eBRCA\u003c/em\u003e mutated recurrent or advanced ovarian cancer responded to olaparib if they failed multiple prior lines of chemotherapy [32, 33]. PARP inhibitors, such as niraparib, rucaparib, and olaparib, are Food and Drug Administration-approved anti-cancer drugs administered after failure of two or three prior lines of treatment in patients with \u003cem\u003eBRCA\u003c/em\u003e-mutated recurrent ovarian cancer. For now, there are no clinical trials available for endometrial carcinoma with \u003cem\u003eBRCA\u003c/em\u003e mutations using PARP inhibitors. The findings of our study may suggest potential management of patients with \u003cem\u003eBRCA\u003c/em\u003e-mutated endometrial carcinoma. Patients could receive individual management if they were stratified based on \u003cem\u003eBRCA\u003c/em\u003e mutation status. In addition, our study revealed that\u003cem\u003e BRCA1\u003c/em\u003e- and/or\u003cem\u003e BRCA2\u003c/em\u003e-mutated endometrial carcinomas had better prognosis than non-carriers, even in high-grade or advanced-stage disease. In the future, our findings could be used for counseling patients on their prognosis.\u003c/p\u003e\n\u003cp\u003eThis study had several limitations, including its retrospective nature and small sample size. Some clinical information, such as family history, was missing. Further studies are necessary to identify differences between prognosis of endometrial carcinomas and germline or somatic \u003cem\u003eBRCA\u003c/em\u003e mutations in larger cohorts.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003ePatients with \u003cem\u003eBRCA1\u003c/em\u003e mutations presented with higher risk endometrial carcinoma than non-carrier group or \u003cem\u003eBRCA2 \u003c/em\u003emutation carriers. \u003cem\u003eBRCA1 \u003c/em\u003eor \u003cem\u003eBRCA2\u003c/em\u003e mutation carriers tended to have more grade 3 endometrioid endometrial carcinoma than non-carrier group. \u003cem\u003eBRCA1\u003c/em\u003e and \u003cem\u003eBRCA2\u003c/em\u003e mutation carriers have more favorable overall survival and progression-free survival among patients with endometrial carcinoma. Independent factors associated with more favorable prognosis for all endometrial adenocarcinomas included \u003cem\u003eBRCA1/2\u003c/em\u003e mutation, \u0026lt;50% myometrial invasion, and negative lymph node status.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e\u003cstrong\u003eFIGO\u003c/strong\u003e: International Federation of Gynecology and Obstetrics\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOS\u003c/strong\u003e: Overall survival\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePFS\u003c/strong\u003e: Progression-free survival\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePARP\u003c/strong\u003e: poly (ADP-ribose)-polymerase\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTCGA\u003c/strong\u003e: The Cancer Genome Atlas\u003c/p\u003e"},{"header":"Declatations","content":"\u003ch2\u003eAuthors contributions\u003c/h2\u003e\n\u003cp\u003eAW analyzed and interpreted the data and was a major contributor in writing the manuscript; AW and RH interpreted the data; ZZ and ZZ abstracted the data; AW designed the work; AW designed the work and interpreted the data. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003ch2\u003eAcknowledgement\u003c/h2\u003e\n\u003cp\u003eWe thank International Science Editing (http://www.internationalscienceediting.com) for editing this manuscript.\u003c/p\u003e\n\u003ch2\u003eEthics approval and consent to participate\u003c/h2\u003e\n\u003cp\u003eThe study was approved by the Ethics Committee of Zhangjiagang Hospital TCM Affiliated to Nanjing University of Chinese Medicine (committee\u0026rsquo;s reference number: 2018-1071). Because all patients involved in TCGA were publicly published. The Ethics Committee approved this consent procedure.\u003c/p\u003e\n\u003ch2\u003eAvailability of data and materials\u003c/h2\u003e\n\u003cp\u003eAll data and materials were from TCGA which was published publicly.\u003c/p\u003e\n\u003ch2\u003eConsent for publication\u003c/h2\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003ch2\u003eCompeting interests\u003c/h2\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003cp\u003e[1] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin.2020;70(1)7-30. doi10.3322/caac.21590.\u003c/p\u003e\n\u003cp\u003e[2] Kuehn B. Uterine Cancer Concern. JAMA.2019;321(4)336. doi10.1001/jama.2018.21059.\u003c/p\u003e\n\u003cp\u003e[3] Furness S, Roberts H, Marjoribanks J, Lethaby A, Hickey M, Farquhar C. Hormone therapy in postmenopausal women and risk of endometrial hyperplasia. 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Ann Oncol.2016;27(6)1013-1019. doi10.1093/annonc/mdw133.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Endometrial carcinoma, BRCA1, BRCA2, prognosis","lastPublishedDoi":"10.21203/rs.3.rs-24271/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-24271/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground:\u0026nbsp;To evaluate Effect of\u0026nbsp;BRCA1\u0026nbsp;and\u0026nbsp;BRCA2\u0026nbsp;mutations on endometrial carcinoma survival rates. \u003c/p\u003e\u003cp\u003eMethods : Data were\u0026nbsp;collected\u0026nbsp;from\u0026nbsp;The Cancer Genome Atlas endometrial cancer database\u0026nbsp;for pathogenic mutations in\u0026nbsp;BRCA1\u0026nbsp;(58) and\u0026nbsp;BRCA2\u0026nbsp;(77), coexisting\u0026nbsp;BRCA1 /2 mutations (40), and non-mutations (461). Clinicopathological features and survival rates were compared. Survival time was analyzed using combined data and Cox proportional hazard models, with\u0026nbsp;BRCA1\u0026nbsp;and\u0026nbsp;BRCA2\u0026nbsp;as time-varying covariates.\u0026nbsp;\u003c/p\u003e\u003cp\u003eResults:\u0026nbsp;Patients with\u0026nbsp;BRCA1\u0026nbsp;mutations presented with higher risk disease (endometrioid endometrial carcinoma grade 3 and uterine serous carcinoma) than non-carriers and\u0026nbsp;BRCA2\u0026nbsp;mutation carriers\u0026nbsp;( p\u0026nbsp;= 0.005 non carriers vs\u0026nbsp;BRCA1\u0026nbsp;mutation carriers,\u0026nbsp;p\u0026nbsp;= 0.008\u0026nbsp;BRCA1\u0026nbsp;mutation carriers\u0026nbsp;vs\u0026nbsp;BRCA2\u0026nbsp;mutation carriers).\u0026nbsp;BRCA1\u0026nbsp;and\u0026nbsp;BRCA2\u0026nbsp;mutation carriers tended to have more endometrioid endometrial carcinoma grade 3 than non-carrier group.\u0026nbsp;Overall survival (OS) rates were higher for all patients with\u0026nbsp;BRCA1\u0026nbsp;and\u0026nbsp;BRCA2\u0026nbsp;mutations than non-carriers. Patients with\u0026nbsp;BRCA2\u0026nbsp;mutations had the most favorable progression-free survival (PFS), followed by patients with\u0026nbsp;BRCA1\u0026nbsp;and\u0026nbsp;BRCA2\u0026nbsp;co-mutations, and then\u0026nbsp;BRCA1 alteration carriers ( p\u0026nbsp;= 0.011).\u0026nbsp;BRCA1/2\u0026nbsp;non-carriers had the worst PFS and OS. \u003c/p\u003e\u003cp\u003eConclusions:\u0026nbsp;Patients with\u0026nbsp;BRCA1\u0026nbsp;mutations presented with higher risk\u0026nbsp;disease than non-carriers and\u0026nbsp;BRCA2\u0026nbsp;mutation carriers.\u0026nbsp;BRCA1\u0026nbsp;and\u0026nbsp;BRCA2\u0026nbsp;mutation carriers\u0026nbsp;had more favorable OS and PFS than non- BRCA\u0026nbsp;mutation carriers in patients with endometrioid endometrial carcinoma and uterine serous carcinoma.\u003c/p\u003e","manuscriptTitle":"Effect of BRCA1 and BRCA2 mutations on endometrial carcinoma survival rates","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2020-04-28 13:41:24","doi":"10.21203/rs.3.rs-24271/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"acc2314f-1cfb-48e1-904a-f70b452d527b","owner":[],"postedDate":"April 28th, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":89901,"name":"Cancer Biology"},{"id":89902,"name":"Oncology"}],"tags":[],"updatedAt":"2020-08-31T15:24:18+00:00","versionOfRecord":[],"versionCreatedAt":"2020-04-28 13:41:24","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-24271","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-24271","identity":"rs-24271","version":["v1"]},"buildId":"FbvkV6FR0MCFSLy54lSbu","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}