Identifying occult maternal malignancies from 1.93 million pregnant women undergoing noninvasive prenatal screening tests.

PURPOSE: Multiple chromosomal aneuploidies may be associated with maternal malignancies and can cause failure of noninvasive prenatal screening (NIPS) tests. However, multiple chromosomal aneuploidies show poor specificity and selectivity for diagnosing maternal malignancies. METHODS: This multicenter retrospective analysis evaluated 639 pregnant women who tested positive for multiple chromosomal aneuploidies on initial NIPS test between January 2016 and December 2017. Women were assessed using genome profiling of copy-number variations, which was translated to cancer risk using a novel bioinformatics algorithm called the cancer detection pipeline (CDP). Sensitivity, specificity, and positive predictive value (PPV) of diagnosing maternal malignancies were compared for multiple chromosomal aneuploidies, the CDP model, and the combination of CDP and plasma tumor markers. RESULTS: Of the 639 subjects, 41 maternal malignant cancer cases were diagnosed. Multiple chromosomal aneuploidies predicted maternal malignancies with a PPV of 7.6%. Application of the CDP algorithm to women with multiple chromosomal aneuploidies allowed 34 of the 41 (83%) cancer cases to be identified, while excluding 422 of 501 (84.2%) of the false positive cases. Combining the CDP with plasma tumor marker testing gave PPV of 75.0%. CONCLUSION: The CDP algorithm can diagnose occult maternal malignancies with a reasonable PPV in multiple chromosomal aneuploidies-positive pregnant women in NIPS tests. This performance can be further improved by incorporating findings for plasma tumor markers.

The role of EpCAM in tumor progression and the clinical prognosis of endometrial carcinoma.

OBJECTIVE: EpCAM is a transmembrane glycoprotein that functions as an epithelial marker in endometrial tissues. However, the correlation between EpCAM and endometrial carcinoma (EC) is not clear. METHODS: This study investigated the association between EpCAM and EC. Immunohistochemistry staining and bioinformatics analysis disclosed the clinical importance of low EpCAM expression. The migratory ability of cells expressing low EpCAM levels was studied in transwell invasion assays in vitro and an orthotopic intra-uterine tumor injection model in vivo. The Connectivity MAP was used to identify drugs that effectively inhibit cells with low EpCAM expression. RESULTS: According to immunohistochemistry analysis results, low EpCAM expression was associated with an advanced stage and lymph node metastasis in patients with endometrioid EC, and high EpCAM expression favored survival. EpCAM silencing promoted cell invasion, and EpCAM re-expression in EpCAM-silenced EC cells attenuated their invasiveness. EpCAM suppression in an orthotopic uterine implantation model promoted the lymph node metastasis of EC cells. According to quantitative PCR and promoter reporter analyses, estrogen receptor alpha signaling regulated EpCAM expression by enhancing its promoter activity. As shown in the Connectivity MAP analysis, transamin inhibited the invasiveness of EpCAM-silenced EC cells. CONCLUSIONS: The loss of EpCAM may increase the malignancy of EC, and these findings provide new insights into the prognostic role of EpCAM in patients with EC.

The H3K9 methyltransferase G9a is a marker of aggressive ovarian cancer that promotes peritoneal metastasis.

BACKGROUND: Ovarian cancer (OCa) peritoneal metastasis is the leading cause of cancer-related deaths in women with limited therapeutic options available for treating it and poor prognosis, as the underlying mechanism is not fully understood. METHOD: The clinicopathological correlation of G9a expression was assessed in tumor specimens of ovarian cancer patients. Knockdown or overexpression of G9a in ovarian cancer cell lines was analysed with regard to its effect on adhesion, migration, invasion and anoikis-resistance. In vivo biological functions of G9a were tested by i.p. xenograft ovarian cancer models. Microarray and quantitative RT-PCR were used to analyze G9a-regulated downstream target genes. RESULTS: We found that the expression of histone methyltransferase G9a was highly correlated with late stage, high grade, and serous-type OCa. Higher G9a expression predicted a shorter survival in ovarian cancer patients. Furthermore, G9a expression was higher in metastatic lesions compared with their corresponding ovarian primary tumors. Knockdown of G9a expression suppressed prometastatic cellular activities including adhesion, migration, invasion and anoikis-resistance of ovarian cancer cell lines, while G9a over-expression promoted these cellular properties. G9a depletion significantly attenuated the development of ascites and tumor nodules in a peritoneal dissemination model. Importantly, microarray and quantitative RT-PCR analysis revealed that G9a regulates a cohort of tumor suppressor genes including CDH1, DUSP5, SPRY4, and PPP1R15A in ovarian cancer. Expression of these genes was also inversely correlated with G9a expression in OCa specimens. CONCLUSION: We propose that G9a contributes to multiple steps of ovarian cancer metastasis and represents a novel target to combat this deadly disease.

Global distribution pattern of histological subtypes of epithelial ovarian cancer: a database analysis and systematic review.

BACKGROUND: Epithelial ovarian cancer is basically a heterogeneous disease with different chemosensitivity and distinct molecular alternations for each histological subtype. In order to assess whether the results of clinical trials can be extrapolated to a new country, it is critical to first examine whether the relative frequencies is homogenous across countries. METHODS: Cancer registry database from a single institution in Taiwan combined with systematic review of the global literature on the relative frequencies of histological subtypes between 2003 and 2012 was provided. RESULTS: Of 175 titles identified, 41 studies met inclusion/exclusion criteria. Globally, for each subtype, the median value of relative frequencies for serous subtype was 45.0%, with the Philippines (16.0%), Indonesia (22.7%), and Brazil (30.1%) as the three lowest countries and South Africa (68.0%), Greece (71.5%), and India (86.7%) as the three highest countries; for mucinous subtype, 11.4%, Italy (3.0%), Australia (3.4%), and Japan (5.4%) were the three lowest countries, while Indonesia (29.1%), Singapore (30.3%), and South Korea (38.6%) were the three highest countries; for endometrioid subtype, 12.6%, India (1.6%), Greece (5.7%), and Portugal (7.6%) were the three lowest countries, while Taiwan (24.8%), Egypt (25.0%), and Austria (25.5%) were the three highest countries; and for clear cell subtype, 5.3%, Pakistan (1.0%), Iran (2.0%), and Brazil (2.1%) were the three lowest countries while Thailand (16.0%), Taiwan (16.8%), and Spain (18.8%) were the three highest countries. CONCLUSIONS: Relative frequencies of subtypes were not homogenous across countries. This diversity may reflect the geographical and ethnic variations. Globally, epithelial ovarian cancer is a heterogeneous disease with a heterogeneous distribution pattern.

Prenatal case of RIT1 mutation associated Noonan syndrome by whole exome sequencing (WES) and review of the literature.

OBJECTIVE: We aimed to identify the genetic cause of one hydrops fetalis with Noonan syndrome (NS) manifestations including increased nuchal translucency (INT) and ascites through prenatal whole exome sequencing (WES). CASE REPORT: The case is a gestational age (GA) 18 fetus of two healthy parents with a normal child. We proceeded the genomic DNA from both fetus amniotic cells and parents to WES and identified a RIT1 mutation (c.268A>G) as the pathogenic cause of the hydrops fetalis by automatic prioritization algorithm after array-comparative genomic hybridization results showing negative. CONCLUSION: Mutations in RIT1 have been reported as the causes for different fetus structural abnormities in the recent years. This case contributes to the summary delineations of the prenatal NS phenotypes related to RIT1 mutation. In addition, the fast WES application, in this case, has demonstrated its advantage in prenatal disorder diagnosis when conventional karyotyping or chromosomal microarray testing result is negative.

Myomectomy for uterine myomas through ultramini-laparotomy.

Uterine fibroids are the most common benign tumors in the female reproductive tract during the reproductive years. Among the options in the treatment spectrum, myomectomy is always considered one of the best choices in the management of women with symptomatic uterine fibroids who wish to preserve future fertility. Myomectomy through conventional exploratory laparotomy may be the most familiar surgical approach. However, with the advances being made in techniques and instruments, there are many alternative approaches to myomectomy, including mini-laparotomy, ultramini-laparotomy, laparoscopy, laparoscopy-aided, and vaginal and hysteroscopic approaches. The focus of this review article is limited to discussing the use of the ultramini-laparotomy approach to completing myomectomy in the management of the uterine fibroids.

Comparing uterine fibroids treated by myomectomy through traditional laparotomy and 2 modified approaches: ultraminilaparotomy and laparoscopically assisted ultraminilaparotomy.

OBJECTIVE: We sought to compare myomectomy performed by laparotomy (LT), and 2 other modified approaches: ultraminilaparotomy (UMLT) and laparoscopically assisted UMLT for uterine fibroids with a size <8 cm and the number <5. STUDY DESIGN: A cohort study, including 79 (35.3%) women in the LT group, 71 (31.7%) in the UMLT group, and 74 (33.0%) in the laparoscopically assisted UMLT group, was conducted. The outcome was measured by comparing surgical parameters, immediate postoperative recovery, and therapeutic outcomes. RESULTS: The median follow-up was 52 months with similar recurrence rates in the 3 groups. The modified approaches had advantages not only in the surgical parameters, but also in postoperative recovery, compared to LT (all P < .05). CONCLUSION: UMLT and laparoscopically assisted UMLT can be used successfully in place of LT in the management of uterine fibroids.

Prevalence of cytomegalovirus DNAemia and genotypic distribution among childbearing mothers and neonates in Taiwan.

BACKGROUND: Congenital cytomegalovirus (CMV) infection is the leading cause of neurologic disabilities and sensorineural hearing loss in children. However, in Taiwan, there is limited information on the genotypic diversity and prevalence of perinatal CMV infection in both mothers and neonates. The aim of this study was to screen samples from both mothers and umbilical cord blood for CMV at the time of delivery and to determine the CMV genotypic distribution. METHODS: Between June 2012 and July 2015, residual maternal and umbilical cord blood samples were collected from consenting participants admitted to the Chang Bing Show Chwan Memorial Hospital in central Taiwan. The blood samples were screened for CMV DNA using real-time PCR assay, and the genotypic classification of the CMV UL55, UL144, and US28 genes was determined by sequencing and phylogenetic analysis. RESULTS: A total of 1282 mother-neonate paired samples were enrolled in the study, 95.3% of whom were Taiwanese. CMV DNA was detectable in 6.2% of the maternal blood samples, with a significantly higher rate noted in non-Taiwanese mothers (11.7%,p=0.027). For the 1,282 umbilical cord blood samples, CMV DNA was detectable in 5.3% of the samples. The presence of CMV DNA in maternal blood was positively associated with the presence of CMV DNA in umbilical cord blood (p=0.01). In addition, the UL55, UL144, and US28 genotypic distribution was similar between mothers and neonates. CONCLUSION: The prevalence of CMV DNAemia in childbearing mothers and neonates is similar and their genotypic distribution implies potential CMV infection during pregnancy.

Neoadjuvant metformin added to conventional chemotherapy synergizes anti-proliferative effects in ovarian cancer.

BACKGROUND: Ovarian cancer is the leading cause of cancer-related death among women. Complete cytoreductive surgery followed by platinum-taxene chemotherapy has been the gold standard for a long time. Various compounds have been assessed in an attempt to combine them with conventional chemotherapy to improve survival rates or even overcome chemoresistance. Many studies have shown that an antidiabetic drug, metformin, has cytotoxic activity in different cancer models. However, the synergism of metformin as a neoadjuvant formula plus chemotherapy in clinical trials and basic studies remains unclear for ovarian cancer. METHODS: We applied two clinical databases to survey metformin use and ovarian cancer survival rate. The Cancer Genome Atlas dataset, an L1000 microarray with Gene Set Enrichment Analysis (GSEA) analysis, Western blot analysis and an animal model were used to study the activity of the AKT/mTOR pathway in response to the synergistic effects of neoadjuvant metformin combined with chemotherapy. RESULTS: We found that ovarian cancer patients treated with metformin had significantly longer overall survival than patients treated without metformin. The protein profile induced by low- concentration metformin in ovarian cancer predominantly involved the AKT/mTOR pathway. In combination with chemotherapy, the neoadjuvant metformin protocol showed beneficial synergistic effects in vitro and in vivo. CONCLUSIONS: This study shows that neoadjuvant metformin at clinically relevant dosages is efficacious in treating ovarian cancer, and the results can be used to guide clinical trials.

Complete remission of heavily treated ovarian clear cell carcinoma with ARID1A mutations after pembrolizumab and bevacizumab combination therapy: a case report.

BACKGROUND: Patients with ovarian clear cell carcinoma (OCCC) have a poor prognosis because they show low sensitivity to platinum-based chemotherapy. New treatments for refractory OCCC are urgently needed. CASE PRESENTATION: We present a patient with refractory OCCC in whom conventional chemotherapy failed. Cachexia was induced by the disseminating recurrent tumors. Tumor tissue staining and genomic analysis revealed PD-L1 negativity, a low tumor burden, stable microsatellite instability, and two mutations in ARID1A. The patient was administered pembrolizumab combined with bevacizumab triweekly. Her serum CA-125 level decreased dramatically after the first cycle. A computerized tomography scan showed marked regression of the recurrent masses after 3 cycles, and the patient reached complete remission after 9 cycles. She showed good recovery from cachexia. We observed no marked side effects except for mild polyarthritis of the small joints. CONCLUSIONS: The therapeutic effect of checkpoint inhibitors combined with angiogenesis inhibitors is very promising in our patient with OCCC. Further clinical trials of tumors including ARID1A mutations are warranted.

Small supernumerary marker chromosome originating from chromosome 10 associated with an apparently normal phenotype.

Small supernumerary marker chromosomes (sSMC) originating from chromosome 10 are rare. Only seven cases have been documented, and among those three cases were diagnosed prenatally. We reported on another prenatal diagnosis of a de novo mosaic sSMC in an apparently normal female fetus whose mother had conceived with assisted reproductive technology (ART) procedures. G-banding analysis of amniotic cells was performed. Spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH) studies with chromosome 10-specific alphoid satellite DNA probe were used to identify the chromosome 10 origin of the sSMC. Further FISH study with telomeric sequence probes showed that the sSMC lacked a hybridization signal, suggesting that the marker could be a ring chromosome. FISH studies using BAC clone probes specific for the regions within 10p11.2, 10q11.1, and 10q11.2 showed that the short arm breakpoint was located between 29.8 and 30.7 Mb from the 10p telomere, and that the long arm breakpoint was located less than 43.6 Mb from the 10p telomere. The karyotype of the fetus was 47,XX,+mar. ish der(10)(SKY+ CEP 10+, CTD-2130I7+, RP11-89J23-)/46,XX. Oligonucleotide microarray-based copy number variations (CNV) analysis was also performed and showed a 6.7 Mb duplication from 10p11.2 to 10q11.2 (36.2-42.9 Mb) with Affymetrix SNP-array 6.0 genotype: arr cgh. 10p11.2q11.2(CN_519687 --> CN_541524) X 3. At the 1-year follow-up, the baby did not have any findings of the trisomy 10p syndrome. This observation provided further credence to the concept that additional chromosome material of proximal 10p11.2 may not contribute to the trisomy 10p syndrome phenotype.

Lamivudine therapy in the treatment of chronic hepatitis B with acute exacerbation during pregnancy.

We report a case of chronic hepatitis B carrier gravida who had acute exacerbation during pregnancy. She had been taking lamivudine 100 mg/qd for 17 months when hepatitis B virus (HBV) DNA in the YMDD region of the polymerase gene (YMDD motif) mutant was noted. After discontinuing lamivudine, she became pregnant. HBeAg became positive again and liver enzymes were elevated during the first trimester of pregnancy. She received the hepatoprotective agent silymarin 150 mg bid at 13+2 gestational weeks. Serum aspartate aminotransferase (AST) dropped to 757 U/L at 15+0 gestational weeks, but serum alanine aminotransferase (ALT) flared up to 2,230 U/L and AST to 2,250 U/L at 17+1 gestational weeks. Serum HBV-DNA test revealed serum HBV-DNA concentration of 7.31 x 10(8) copies/mL. Lamivudine 100 mg/qd and silymarin 150 mg/bid were initiated at 17+1 gestational weeks. Liver function showed gradual decline to ALT 341 U/L and AST 91 U/L at 21+0 gestational weeks, while HBeAg(+) converted to (-) and anti-HBe(-) converted to (+). Further treatment with lamivudine 100 mg/qd continued for 3 months. Serum HBV-DNA concentrations decreased to 3.19 x 10(2) copies/mL at 36+6 gestational weeks. Spontaneous delivery of a male baby weighing 3314 g occurred at 38+3 gestational weeks. The neonatal physical check-up revealed no congenital anomalies, and fetal growth was within normal reference ranges, suggesting that lamivudine may be safely used in the treatment of chronic hepatitis B with acute exacerbation during the second trimester of pregnancy.

Crosstalk between SOX2 and cytokine signaling in endometrial carcinoma.

Endometrial carcinoma is a cancer derived from oncogenesis of the regenerating uterine cavity, in which cytokine stimulation shapes cell differentiation and tissue remodeling. Expression of the stem cell factors SOX2, OCT4, NANOG, and MYC has been linked to tumor malignancy in several cancers. However, how these stem cell factors crosstalk with cytokine signaling to promote malignancy in endometrial carcinoma is still elusive. Here we report that the expression of SOX2 and MYC, but not that of OCT4 and NANOG, correlate with poor histological differentiation and prognosis, while SOX2 expression is negatively associated with MYC level. We found that SOX2-high endometrial carcinoma cells possessed a higher colony-forming ability than their SOX2-low counterparts, and knockdown of SOX2 attenuated the colony-forming ability. We observed that SOX2 regulated EGFR expression in a SOX2-EGFR positive feedback loop. EGF stimulation induced SOX2 expression and promoted migration of endometrial carcinoma cells, whereas TGF-ß stimulation inhibited SOX2 expression and attenuated the colony-forming ability. Immunohistochemistry analysis revealed that SOX2 expression correlated with lymph node infiltration of endometrial carcinoma. Our findings support that cytokine-induced stem cell factor SOX2 possesses oncogenic properties, with the potential to serve as a prognostic biomarker in endometrial carcinoma.

The role of α2,3-linked sialylation on clear cell type epithelial ovarian cancer.

OBJECTIVE: Our previous study has shown that high expression of α2,3-sialytransferase type I was associated with advanced stage serous type epithelial ovarian cancer (EOC). The aim of the current study further attempts to evaluate the altered α 2,3-sialylation on the behavior of clear cell type EOC (C-EOC). MATERIALS AND METHODS: Immunohistochemistry staining, bioinformatics analysis and tissue array were used to disclose the clinical significance of over α2,3-sialylation in C-EOC. An α2,3 sialylation inhibitor, soyasaponin I (SsaI) was used to investigate the behavior change of the C-EOC cell line. RESULTS: We reconfirmed that α2,3-sialylation, instead of α2,6- sialylation, was associated with late-stage C-EOC. Soyasaponin I could inhibit α2,3-sialylation of C-EOC cell lines and increase E-cadherin expression with subsequently suppressing migration of C-EOC cells. CONCLUSIONS: The current study demonstrated the important role of α2,3-linked sialylation in C-EOC and targeting of α2,3-linked sialylation might offer as a potential therapeutic strategy in the future.

A case-control study to compare the outcome of women treated by two minimally invasive procedures-ultraminilaparotomy myomectomy and laparoscopic myomectomy.

OBJECTIVE: Ultraminilaparotomy myomectomy (UMLT-M with less 4 cm transverse skin incision) and conventional 3-port wound laparoscopic myomectomy (LM) approaches were proposed as alternative minimally invasive procedures in the management of women with symptomatic uterine myomas but few studies have compared the outcomes of both procedures. MATERIALS AND METHODS: Between January 2002 and December 2003, 71 patients undergoing UMLT-M were compared with those 71 women undergoing LM. The last data collection for all patients was done on 31 December 2016. The parameters for comparison included the characteristics of the uterine myomas, surgical parameters, morbidities, and outcomes. Surgical parameters included the operative time (minutes), estimated blood loss (milliliters), time for removal of drainage, percentage of blood transfusion and co-morbidities. RESULTS: Mean operative time in the LM group was significantly longer than that in the UMLT-M group (208.7 ± 65.9 vs. 98.0 ± 28.2 min, p < 0.001). Intra-operative blood loss was significantly higher in the LM group than that in the UMLT-M group (210.9 ± 184.5 vs. 111.7 ± 108.4 ml, p < 0.001). However, more patients had postoperative fever in the UMLT-M group (39.4% vs. 8.5%, p < 0.001). The recurrence rate of myoma at 5-year follow-up was significantly different between two groups (35.2% of UMLT-M vs. 57.7% of LM, p = 0.007), but there was no difference when follow-up time was over ten years. The location of the myoma recurrence was different between two groups with higher recurrence rates in the fundal and lateral sides of uterus in the UMLT-M group and in the anterior wall of uterus in the LM group. However, the overall symptom control, the need of repeated myoma-related surgery and subsequent pregnancy outcome of both groups seemed to be similar in both groups. CONCLUSIONS: More operative time and more blood loss reflected that LM demanded skills, experience and equipment. Therefore, UMLT-M might be a feasible alternative choice in the management of uterine myomas, since it is an easy-to-perform and familiar technique, especially in the absence of suitable equipment or skilled operator. A large and randomized study is needed to confirm the above findings.

Copy number variation profile in noninvasive prenatal testing (NIPT) can identify co-existing maternal malignancies: Case reports and a literature review.

OBJECTIVE: The coexistence of maternal malignancy and pregnancy has received increasing attention in Noninvasive prenatal testing (NIPT) studies. Malignancy in pregnant women potentially affects the copy number variation (CNV) profile in NIPT results. Only one case of hematologic cancer has been reported in a Hong-Kong pregnant women, and solid tumors have never been reported in pregnant Chinese women. CASE REPORT: The patients with dysgerminoma and cervical cancer showed aberrant chromosomal aneuploidies in NIPT and concordant patterns of genome disruption in tumor tissues. The genomic aberrations in the gastric cancer patient had similar copy number variation pattern of gastric cancer. CONCLUSION: The findings in this study and the literature review further validate the effect of maternal malignancy on the copy number variation profile in NIPT data and strengthen the possibility of detecting malignant tumors with NIPT in the future.

α2,3-sialyltransferase type I regulates migration and peritoneal dissemination of ovarian cancer cells.

Epithelial ovarian cancer (EOC) has the highest mortality rate among gynecologic cancers due to advanced stage presentation, peritoneal dissemination, and refractory ascites at diagnosis. We investigated the role of α2,3-sialyltransferase type I (ST3GalI) by analyzing human ovarian cancer datasets and human EOC tissue arrays. We found that high expression of ST3GalI was associated with advanced stage EOC. Transwell migration and cell invasion assays showed that high ST3GalI expression enhanced migration of EOC cells. We also observed that there was a linear relation between ST3GalI expression and epidermal growth factor receptor (EGFR) signaling in EOC patients, and that high ST3GalI expression blocked the effect of EGFR inhibitors. Co-Immunoprecipitation experiments demonstrated that ST3GalI and EGFR were present in the same protein complex. Inhibition of ST3GalI using a competitive inhibitor, Soyasaponin I (SsaI), inhibited tumor cell migration and dissemination in the in vivo mouse model with transplanted MOSEC cells. Further, SsaI synergistically enhanced the anti-tumor effects of EGFR inhibitor on EOC cells. Our study demonstrates that ST3GalI regulates ovarian cancer cell migration and peritoneal dissemination via EGFR signaling. This suggests α2,3-linked sialylation inhibitors in combination with EGFR inhibitors could be effective agents for the treatment of EOC.

The frequency of cancer predisposition gene mutations in hereditary breast and ovarian cancer patients in Taiwan: From BRCA1/2 to multi-gene panels.

An important role of genetic factors in the development of breast cancer (BC) or ovarian cancer (OC) in Taiwanese (ethnic Chinese) patients has been suggested. However, other than germline BRCA1 or BRCA2 mutations, which are related to hereditary breast-ovarian cancer (HBOC), cancer-predisposition genes have not been well studied in this population. The aim of the present study was to more accurately summarize the prevalence of genetic mutations in HBOC patients using various gene panels ranging in size from BRCA1/2 alone to multi-gene panels. Among 272 HBOC patients analyzed, the prevalence of BRCA1, BRCA2 and non-BRCA1/2 pathogenic mutations was 7.7% (21/272), 6.8% (16/236) and 8.2% (13/159), respectively. The total mutation rate was 18.4% (50/272). Although no founder mutations were identified in this study, two recurrent mutations, BRCA1 (c.3607C>T) and BRCA2 (c.5164_5165 delAG), were found. The main pathogenic/likely pathogenic mutations in non-BRCA1/2 genes included ATM, BRIP1, FANCI, MSH2, MUYTH, RAD50, RAD51C and TP53. The prevalence rate of gene mutations in HBOC patients did not differ with respect to whether BC or OC was the first diagnosis or they presented a family history of the disease or their age at diagnosis. HBOC patients with both BC and OC exhibited a higher prevalence rate of mutations (50.0%) than patients with OC (25.0%) or BC (8.6%) alone. In conclusion, evaluation of hereditary cancer risk in Taiwan HBOC patients, particularly individuals with double cancer, is strongly encouraged. Panel testing can yield additional genomic information, and widespread and well-designed panel testing will help in assessing more accurate mutational prevalence of risk genes.