Chemotherapy Use Is a Significant Predictor for Sexual Dysfunction in Women with Gynecologic Cancer

Objectives: Sexual dysfunction is a significant survivorship issue in women with gynecologic cancer. We examined the association between chemotherapy and impaired sexual functioning. Methods: A cross sectional study of women with gynecologic cancer was conducted with a 181-item survey of validated instruments. A sub-analysis of women with chemotherapy treatment was performed to examine factors associated with sexual function including age, menopause status, BMI, diagnosis, stage, surgery/radiation use, active disease status, number of regimens, and number of cycles. Sexual dysfunction was measured by change in the Female Sexual Function Index (FSFI) score from pre-treatment with a significant decline in sexual function determined to be a 5.6 point decrease using a Reliable Change Index Statistic (RCIS). Standard statistical tools were employed. Results: A total of 107 (63%) of the women in the larger study had received chemotherapy as part of their treatment and were included in the sub-study. Women undergoing chemotherapy were more likely to experience sexual dysfunction post-treatment (51% vs. 26%;OR 2.9, 95% CI 1.5 - 5.7). In bivariate analyses, sexual dysfunction following chemotherapy was associated with age Conclusions: Women treated with chemotherapy for gynecologic cancer are at a significant risk of impaired sexual function. Women with cervical cancer, early stage disease, those who are premenopausal, and those younger than age 50 are at the highest risk.

Phase 1/2 study of concurrent chemoradiotherapy with weekly irinotecan hydrochloride for advanced/recurrence uterine cancer:A multi-institutional study of Kansai Clinical Oncology Group

Objective:Concurrent chemoradiotherapy using cisplatin was thought to be standard treatment for squamous cell carcinoma of cervix,but it had not been effective for adenocarcinoma.Concurrent chemoradiotherapy using irinotecan hydrochloride(CPT-11)had been effective for colorectal cancer,thus,we chose CPT-11 as a candidate for gynecologic adenocarcinoma.To evaluate the maximum tolerated dose(MTD)of weekly CPT-11 with external pelvic radiotherapy,a phase 1/2 study was conducted according to modified Fibonacci method.Methods:Eligible patients were advanced uterine cancer with measurable diseases[performance score(PS):0-2].Study period was from August 1 st,2002 to December 31 st,2008.The starting dose level(DL)of CPT-11 was 30 mg/m2(DL1)given weekly for 4 weeks.Subsequently,dose escalation was scheduled in 10 mg/m2 increments to 60 mg/m^2(DL4).The fixed radiotherapy consisted of whole pelvic 1.8 Gy/d,once a day in weekday for five weeks and it amounted to 45 Gy(25 fractions)in total.Results:Seventeen patients were enrolled.As for toxicities,one(1/17:5.9%)grade(G)4 neutropenia lasting 7 days had been seen in DL4.G2 diarrhea was identified in 35.3%(6/17)of the patients,and 11.8%(2/17)G3 diarrhea was observed in DL3 and DL4.Thus,the MTD of CPT-11 was defined as dose of 60 mg/m^2.The recommended dose was decided as 50 mg/m^2.The response rate was 88.2%[9 complete response(CR),3 partial response(PR),3 stable disease(SD),2 not evaluable(NE)].Disease control rate at 1 month after treatment completion was 100%but distant metastases were found in 24%(4/17)in longer outcome.Conclusions:MTD was 60 mg/m^2 and recommended dose was set as 50 mg/m2.This concurrent chemoradiation using weekly CPT-11 was feasible at 50 mg/m^2,and it might be effective even in adenocarcinoma of the uterus.

Care of survivors of gynecologic cancers

The number of cancer survivors is increasing and most healthcare providers will manage patients who have completed therapy for malignancy at some point. The care of survivors of gynecologic malignancies may seem daunting in a busy general gynecology practice. This paper intends to review the literature and suggest management of these women for the general gynecologist.

晚期卵巢癌、输卵管癌及原发性腹膜癌腹腔镜肿瘤细胞减灭术的安全性及有效性研究

目的总结晚期卵巢癌、输卵管癌和腹膜癌患者行腹腔镜初次或间歇性肿瘤细胞减灭术的临床经验。方法回顾分析接受腹腔镜肿瘤细胞减灭术的晚期卵巢癌(FIGOⅡc期以上)、输卵管癌和原发性腹膜癌患者临床资料。结果 32名患者接受腹腔镜评估手术。17例接受全腹腔镜肿瘤细胞减灭术,其中88.2%为满意的肿瘤细胞减灭术;11例腹腔镜评估后转开腹肿瘤细胞减灭术,其中72.7%为满意的肿瘤细胞减灭术;4例仅进行活检和(或)姑息手术。腹腔镜组平均随访时间19.7月9,例无瘤生存6,例带瘤生存2,例因肿瘤死亡。开腹组平均随访时间25.8月,3例无瘤生存,5例带瘤生存,3例因肿瘤死亡。腹腔镜组术中失血量较少,术后住院时间较短(P=0.008和P=0.03),但手术时间及并发症发生率与开腹组相比无统计学差异。中位复发时间,腹腔镜组为31.7月,开腹组为21.5个月(P=0.3)。结论对于经过精心挑选的晚期卵巢癌、输卵管癌和原发性腹膜癌病例,采用腹腔镜进行诊断、分期和肿瘤细胞减灭术,在技术上是可行的。

Biology, staging, and treatment of breast cancer during pregnancy: reassessing the evidences

Breast cancer is one of the most frequently diagnosed malignancies during pregnancy. Here, we review the management of women with breast cancer during pregnancy(BCP), focusing on biology, diagnosis and staging, local and systemic treatments, obstetric care and long-term follow-up of children with prenatal exposure to anticancer treatments.

WJBC 5^(th) Anniversary Special Issues(2): Proteomics In 2014, can we do better than CA125 in the early detection of ovarian cancer?

Ovarian cancer is a lethal gynecologic malignancy with greater than 70% of women presenting with advanced stage disease. Despite new treatments, long term outcomes have not significantly changed in the past 30 years with the five-year overall survival remaining between 20% and 40% for stage Ⅲ and Ⅳ disease. In contrast patients with stage Ⅰ disease have a greater than 90% five-year overall survival. Detection of ovarian cancer at an early stage would likely have significant impact on mortality rate. Screening biomarkers discovered at the bench have not translated to success in clinical trials. Existing screening modalities have not demonstrated survival benefit in completed prospective trials. Advances in high throughput screening are making it possible to evaluate the development of ovarian cancer in ways never before imagined. Data in the form of human "-omes" including the proteome, genome, metabolome, and transcriptome are now available in various packaged forms. With the correct pooling of resources including prospective collection of patient specimens, integration of high throughput screening, and use of molecular heterogeneity in biomarker discovery, we are poised to make progress in ovarian cancer screening. This review will summarize current biomarkers, imaging, and multimodality screening strategies in the context of emerging technologies.

Evolution of radical hysterectomy for cervical cancer along the last two decades: single institution experience

Background： The radical hysterectomy （RH） surgical technique has improved along the years. It is used for the treatment of cervical cancer, endometrial cancer when affecting the cervix, and upper vaginal carcinomas. Our aim was to describe the historical evolution of the technique after the introduction of laparoseopy at our institution. Methods： We performed a retrospective review of medical records of patients who underwent RH, grouped in three periods according to the year of surgery： 1990-1999, 2000-2009 and 2010-2013. Patients＇ characteristics, pathologic details, intraoperative and postoperative complications were analyzed and comoared throughout the time periods. Results： A total of 102 cases of RH were performed at our center during the study period. Among all data collected, the presence of necrosis, age, number of lymph nodes, surgery route, operating time, hospital stay, blood loss and transfusion requirement were statistically significant different among groups. Conversion to laparotomy rate was 19% for the second period compared to the absence of cases in the last one. No significant differences （P=0.124） were observed in the adjuvant treatment received among the three different groups. At the time of the last contact the patients free of disease were 12 （85.7%）, 53 （91.3%） and 26 （86.6%） respectively （P=0.406）. Regarding the disease-free interval, we found significant better outcomes in the group of laparotomy compared to laparoscopy （P=0.015）.Conclusions： Laparoscopic RH is an acceptable surgery with advantages like magnified vision of the operation＇s field, lower surgical complications, shorter hospital stay and earlier resumption to daily activities.

IGHG1 promotes motility likely through epithelial-mesenchymal transition in ovarian cancer

Objective： Ovarian cancer（OC） is one of the leading causes of death for female cancer patients. COC166-9 is an OC-specific monoclonal antibody and we have identified immunoglobulin γ-1 heavy chain constant region（IGHG1） as its antigen. We explore the function of IGHG1 in proliferation, apoptosis and motility of OC cells further in this research.Methods： IGHG1 expression in OC specimens was detected through immunohistochemistry. Real-time quantitative polymerase chain reaction（RT-q PCR） or western blotting assay was used to test IGHG1 expression in OC cells. Viability of OC cells was tested by 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide（MTT）assay. Flow cytometry or western blotting assay was used to detect cell cycle and apoptosis. Cellular motility was analyzed by using transwell assay and the markers of epithelial-mesenchymal transition（EMT） were tested through immunoblots.Results： Although it exerts negligible effect on the viability and apoptosis of OC cells, IGHG1 could promote migration and invasion of malignant cells in vitro. Mechanistically, IGHG1 increases the expression of N-cadherin and Vimentin while decreases E-cadherin expression. Additionally, IGHG1 expression in OC specimens is higher relative to the paired normal counterparts. Further analysis demonstrates that the increased IGHG1 expression correlates positively with the lymph node metastasis of OC.Conclusions： IGHG1 promotes the motility of OC cells likely through executing the EMT program. Increased IGHG1 expression in OC specimens is associated with the lymph node metastasis.

Preoperative markers for the prediction of high-risk features in endometrial cancer

BACKGROUND Preoperative evaluations aiming to assess high-risk features in clinical stage 1 endometrial cancer patients are crucial to refer these patients to gynecologic oncologists.Cancer antigen 125(CA125)and human epididymis protein 4(HE4)have been reported in endometrial cancer patients with poor prognostic factors.AIM To evaluate the association between preoperative levels of CA125 and HE4 and high-risk features and establish optimal cut-off values in clinical stage 1 endometrial cancer.METHODS A retrospective study was conducted in clinical stage 1 endometrial cancer patients who underwent primary surgery between January 2013 and December 2018.A total of 128 patients had preoperative serum CA125 and HE4 measurements.High-risk features included grade 3 tumors,large tumor sizes(more than 2 cm),deep myometrial invasion(more than 50%),lymphovascular space invasion(LVSI),cervical involvement,extrauterine involvement and node metastasis.Receiver operating characteristic(ROC)curves were generated to analyze the optimal cut-off values.RESULTS The mean age of the patients was 57.4 years,and 69.5%of them were postmenopausal.Most patients presented with stage I disease(67.2%)and had the endometrioid subtype(97.7%).The median CA125 and HE4 levels in all patients were 22.1 U/mL and 104.7 pmol/L,respectively.CA125 and HE4 levels were significantly elevated in those with large tumor sizes,deep myometrial invasion,LVSI,extrauterine metastasis,and advanced stage,but node metastasis was associated with elevated CA125 only.According to the ROC curve,both serum markers had statistical significance for the prediction of high-risk features only in postmenopausal patients,with an optimal cut-off value of 20 U/mL for CA125[area under the concentration-time curve(AUC)=0.72,P=0.002]and 113 pmol/L for HE4(AUC=0.70,P=0.006).The combination of both serum markers had 80%sensitivity and 64.4%positive predictive value.Significantly worse 5-year disease-free survival was observed in patients with high levels of CA125 and HE4(78.4%and 100%,respectively;P=0.01).CONCLUSION Preoperative CA125 levels greater than 20 U/mL or HE4 levels greater than 113 pmol/L are associated with an increased risk of having high-risk features and present as prognostic factors in clinical stage 1 postmenopausal endometrial cancer patients.This information is helpful for general gynecologists to refer high-risk patients to gynecologic oncologists to perform complete surgical staging.

The Development of the Qatar Healthcare System: A Review of the Literature

Background: Qatar, one of the smallest and wealthiest countries in the world, is a newly emerging healthcare system. Medical leadership in Qatar has had to create an infrastructure for medical care over the past twenty years. The purpose of this paper is to review the challenges and achievements of the newly emerging Qatar healthcare system. Methods: PubMed was searched using MESH terms: Qatar, healthcare, medical development, medical insurance and medical history. Websites of the World Bank, CIA fact book, Qatar Ministry of Health, Hamad Medical Corporation, Organization for Economic Co-operation and Development and the US State department were searched for information about Qatar’s healthcare system and its history. Results: Qatar is a rapidly growing, multicultural country with over 80 nationalities represented. Qatar has developed a healthcare system with universal coverage. Up until 2014, the government has subsidized all care. There are plans to develop a medical insurance system. Conclusions: Qatar has experienced the rapid development of a healthcare system over the past twenty years. The government has centrally controlled growth and development. An examination of the unique challenges to building a Qatari healthcare system will be useful in considering how to develop medical infrastructure in other countries.

Expression of O⁶-Methylguanine-DNA Methyltransferase Examined by Alkyl-Transfer Assays, Methylation-Specific PCR and Western Blots in Tumors and Matched Normal Tissue

The tumor selectivity of alkylating agents that produce guanine O6-chloroethyl (laromustine and carmustine) and O6-methyl (temozolomide) lesions depends upon O6-methylguanine-DNA methyltransferase (MGMT) activity being lower in tumor than in host tissue. Despite the established role of MGMT as a tumor resistance factor, consensus on how to assess MGMT expression in clinical samples is unsettled. The aim of this study is to examine the relationship between the values derived from distinctive MGMT measurements in 13, 12, 6 and 2 pairs of human tumors and matched normal adjacent tissue from the colon, kidney, lung and liver, respectively, and in human cell lines. The MGMT measurements included 1) alkyl-transfer assays using [benzene-3H]O6-benzylguanine as a substrate to assess functional MGMT activity, 2) methylation-specific PCR (MSP) to probe MGMT gene promoter CpG methylations as a measure of gene silencing, and 3) western immunoblots to analyze the MGMT protein. In human cell lines, a strict negative correlation existed between MGMT activity and the extent of promoter methylation. In tissue specimens, by contrast, the correlation between these two variables was low. Moreover, alkyl-transfer assays identified 3 pairs of tumors and normal tissue with tumor-selective reduction in MGMT activity in the absence of promoter methylation. Cell line MGMT migrated as a single band in western analyses, whereas tissue MGMT was heterogeneous around its molecular size and at much higher molecular masses, indicative of multi-layered post-translational modifications. Malignancy is occasionally associated with a mobility shift in MGMT. Contrary to the prevalent expectation that MGMT expression is governed at the level of gene silencing, these data suggest that other mechanisms that can lead to tumorselective reduction in MGMT activity exist in human tissue.

Cytoreductive surgery in primary advanced epithelial ovarian cancer

Epithelial ovarian cancer is one of the most common malignancy and one of the principal causes of death among gynaecological neoplasm. The majority of patients(about 70%) present with an advanced International Federation of Gynaecology and Obstetrics stage disease. The current standard treatment for these patients consists of complete cytoreduction and combined systemic chemotherapy(CT). An increasing proportion of patients undergoing complete cytoreduction to no gross residual disease(RD) is associated with progressively longer overall survival. As a counterpart, some authors hypothesized the improving in survival could be due more to a less diffused initial disease than to an increase in surgical cytoreduction rate. Moreover the biology of the tumor plays an important role in survival benefi t of surgery. It's still undefi ned how the intrinsic features of the tumor make intra-abdominal implants easier to remove.Adjuvant and hyperthermic intraperitoneal CT could play a decisive role in the coming years as the completeness of macroscopic disease removal increases with advances in surgical techniques and technology. The introduction of neo-adjuvant CT moreover will play a decisive role in the next years Anyway cytoreduction with no macroscopic residual of disease should always be attempted. However the defi nition of RD is not universal. A unique and defi nitive defi nition is needed.

空卵泡内卵母细胞:一种存在争议的综合征

To assess the prevalence and etiology of the empty follicle syndrome (EFS). Design: Observational longitudinal study. Setting: Tertiary fertility centers. Patient(s): All patients beginning in vitro fertilization (IVF) treatment from December 2002 to November 2004 were included. Couples undergoing IVF with donor oocytes or participating in an experimental IVF study were excluded from analysis. Intervention(s): Identification of EFS cycles. Comparing ovarian hyperstimulation strategy, follicle count, and timing of human chorionic gonadotropin (hCG) for final oocyte maturation of the EFS cycles with normal IVF cycles. Main Outcome Measure(s): Number of follicles punctured, number of oocytes recovered, previous and future IVF attempts, and serum hormone levels. Result(s): Twenty-five of a total of 1,849 patients were identified with an EFS cycle. Reasons for occurrence of EFS cycles were mistiming of hCG for final oocyte maturation, premature ovulation, and poor ovarian response. None of the affected patients had experienced EFS cycles in earlier IVF attempts nor were there any recurrence in subsequent treatments. Conclusion(s): Accurate timing of induction of final oocyte maturation, properly scheduled ovarian hyperstimulation, instruction of patients and doctors, and full workup for IVF are essential for the successful recovery of oocytes. Occurrence of EFS in IVF can normally be attributed to a failure of at least one of these factors and probably rarely or never occurs otherwise.

切除腹膜的肿瘤细胞减灭术和腹腔温热灌注化疗后自然妊娠

Spontaneous pregnancy is rare after radical cytoreduction and intraperitoneal chemotherapy. Case. We present a case of a 28- year-old female with extensive, bulky malignant peritoneal epitheliod mesothelioma who underwent optimal cytoreductionwith peritonectomy followed by intraoperative hyperthermic cisplatin and postoperative intraperitoneal paclitaxel and fluorouracil. Fourteen months after the conclusion of her therapy, she spontaneously conceived, resulting in an uneventful term pregnancy and spontaneous vaginal delivery. Conclusion. Fertility may be preserved in select patients after radical cytoreduction and hyperthermic intraperitoneal chemotherapy.

高危型人乳头瘤病毒(HR-HPV)DNA在意义不明的非典型性鳞状细胞(ASC-US)巴氏涂片中的阳性率报道:一项军队人群调查

Objective. To determine the prevalence of HR- HPV DNA in ASC- US Pap smears following implementation of the Bethesda 2001 classification system. Methods. A computer database of Pap smears obtained within Department of the Army medical facilities was queried for the study period August 2002 to June 2004. All ASC- US Pap smears that underwent reflex testing for HR- HPV DNA were included. Additional clinical and demographic data were obtained from facilities within the US northeast region to evaluate the differences in ASC- US and SIL rates between the current and former Bethesda classification systems. Results. 550,000 Pap smears were collected during the study period. The HR- HPV prevalence was 40.8% (95% confidence interval [CI] = 40.3 to 41.3) among 40,870 patients with ASC- US Pap smears. Within the northeast region, the HR- HPV prevalence in ASC- US Pap smears decreased from 61.2% (95% CI = 57.4 to 64.8% ) in patients 18- 22 years old to 24.9% (95% CI = 23.1 to 26.8% ) in patients age 29 and older. When comparing the two classification systems, significant increases in both ASC- H and SIL and decreases in ASC- US were appreciated after the institution of Bethesda system 2001. Conclusion. In our large, diverse cohort, the implementation of the Bethesda II system has resulted in a decrease in ASC- US Pap smear results. Additionally, the prevalence of HR- HPV in theASC- US population was 40.8% , significantly lower than the rate noted in the ALTS trial under the Bethesda I classification system.

How does ethanol induce apoptotic cell death of SK-N-SH neuroblastoma cells?

A body of evidence suggests that ethanol can lead to damage of neuronal cells. However, the mechanism underlying the ethanol-induced damage of neuronal cells remains unclear. The role of mitogen-activated protein kinases in ethanol-induced damage was investigated in SK-N-SH neuroblastoma cells. 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide cell viability assay, DNA fragmentation detection, and flow cytometric analysis showed that ethanol induced apoptotic cell death and cell cycle arrest, characterized by increased caspase-3 activity, DNA fragmentation, nuclear disruption, and G1 arrest of cell cycle of the SK-N-SH neuroblastoma cells. In addition, western blot analysis indicated that ethanol induced a lasting increase in c-Jun N-terminal protein kinase activity and a transient increase in p38 kinase activity of the neuroblastoma cells. c-Jun N-terminal protein kinase or p38 kinase inhibitors significantly reduced the ethanol-induced cell death. Ethanol also increased p53 phosphorylation, followed by an increase in p21 tumor suppressor protein and a decrease in phospho-Rb （retinoblastoma） protein, leading to alterations in the expressions and activity of cyclin dependent protein kinases. Our results suggest that ethanol mediates apoptosis of SK-N-SH neuroblastoma cells by activating p53-related cell cycle arrest possibly through activation of the c-Jun N-terminal protein kinase-related cell death pathway.

Sentinel lymph node mapping of a breast cancer of the vulva: Case report and literature review

Ectopic breast tissue is rare and typically presents as an axillary mass. Previous reports have identified ectopic breast tissue in the vulva, but malignancy is exceedingly uncommon. We present a 62 years old with locally advanced breast carcinoma arising in the vulva demonstrates the utilization of sentinel lymph node mapping to identify metastatic lymph nodes previously unable to be identified via traditional surgical exploration.Our case supports the principles of adjuvant therapy for breast cancer to be applied to ectopic breast cancer arising in the vulva. A literature review highlights common key points in similar cases to guide management.

Is Peritoneal Cytology a Prognostic Factor in Endometrial Cancer?

The International Federation of Gynecology and Obstetrics (FIGO) changed the surgical staging criteria for endometrial cancer in 2009, namely combining FIGO 1988 Stage IA and IB in FIGO 2009 Stage IA, eliminating cervical glandular involvement from Stage II, and removing peritoneal cytology as criteria from Stage IIIA (3). This review of the literature sheds light on the continued debate among authorities on the utility of peritoneal cytology in surgical staging of endometrial cancer. At the time FIGO removed peritoneal cytology from the staging criteria in 2009, there was little to no evidence to support its removal. In fact, FIGO continues to recommend obtaining peritoneal cytology, which is in contradiction to their staging criteria. While a few small studies support the idea that peritoneal cytology does not preclude a worse prognosis, a number of large scale studies with at least 300 patients demonstrate a clear association between survival and the presence of malignant peritoneal cytology (11 - 12, 15 - 19). In one of the largest studies, investigators reviewed 14,704 from the SEER’s database, demonstrating that malignant peritoneal cytology is associated with decreased survival across Stage I/II disease even when controlled for histology, grade, and other risk factors. Malignant peritoneal cytology should be considered when counseling patients on the risk of recurrence and overall survival of endometrial cancer. However, the role of adjuvant treatment in this setting remains unclear.

Current Possible Drug Therapies for Ovarian Cancer

Ovarian cancer is the most aggressive gynecologic cancer of the heterogenous phenotypes. Development of the new chemotherapeutic agents and drug delivery mode makes better outcomes for patient treatments. Optimal cytoreductive therapy followed by molecular targeting therapy, intraperitoneal chemotherapy and dose dense chemotherapy is a hot therapeutic concept in ovarian cancers. In our review, we will introduce recent therapeutic advances in epithelial ovarian cancer patients.

Germline mutations in Thai patients with nonmucinous epithelial ovarian cancer

BACKGROUND Genetic testing is widely recommended for all epithelial ovarian cancer(EOC)patients.However,an increased probability of identifying germline mutations has been reported in selected patients with risk factors such as a family history or personal history of cancer and high-grade serous carcinoma(HGSC)subtype.HGSC has been reported to be the most common subtype of EOC worldwide(approximately 70%).However,this subtype is less prevalent in Thai patients(reported as only 20%).The difference in the distribution of various subtypes of EOC may reflect the incidence of germline mutations in Thai EOC patients.AIM To evaluate the frequencies of germline mutations in EOC patients and to compare the frequencies in those with and without clinical risk factors for hereditary ovarian cancer.METHODS This cross-sectional study included 112 nonmucinous EOC patients who underwent primary surgery at our tertiary care hospital.Clinical risk factors for hereditary ovarian cancer were defined as follows:Age below 40 years,a significant family history of cancer,synchronous ovarian and endometrial cancer,and HGSC.Comprehensive germline mutations were detected by nextgeneration sequencing.RESULTS Of a total of 112 patients,82(73.2%)patients had≥1 risk factor and 30(26.8%)patients had no risk factors.Germline mutations were detected in 26 patients:20(17.8%)patients had BRCA1/2 mutations,but 6(5.4%)patients had mutations in other genes,including 1 in MLH1,1 in MSH2,1 in RAD51C,2 in ATM and 1 in CDH1.Germline mutations were only detected in patients with risk factors(26 of 82,31.7%),not in patients without risk factors(P<0.001).A significant family history of cancer and HGSC were the only two significant risk factors associated with a higher proportion of germline mutations(56.3%vs 10%for those with and without a history of cancer,respectively,40.8%vs 9.5%for those with and without HGSC).Germline BRCA mutations were detected in 38.8%of patients with HGSC but in only 1.6%of those with non-HGSC.An age below 40 years,personal history of breast cancer,and synchronous ovarian and endometrial cancer were not significant factors(14.3%vs 23.5%,33.3%vs 21%,22.2%vs 22.3%).CONCLUSION Approximately one-third of EOC patients with risk factors had germline mutations.Almost all germline BRCA mutations were found in patients with the HGSC subtype.Selected patients with HGSC and a family history of cancer should be initially considered for genetic analysis in Thailand.