Risk Of Ovarian Cancer Research Articles

Fiber-type prebiotics and gynecological and breast cancers risk: the PrebiotiCa study.

Prebiotics may influence the risk of hormone-related female cancers by modulating the gut microbiota involved in estrogens metabolism. We evaluated the association of fiber-type prebiotic intake with breast, endometrial, and ovarian cancers. Data derived from a network of Italian hospital-based case-control studies (1991-2006), including 2560 cases of cancer of the breast (2588 controls), 454 of the endometrium (908 controls) and 1031 of the ovary (2411 controls). Inulin-type fructans (ITFs), and selected fructo-oligosaccharides (FOSs, nystose, kestose and 1F-β-fructofuranosylnystose) and galacto-oligosaccharides (GOSs, raffinose and stachyose) were quantified in food products. Prebiotic intake was estimated by multiplying food frequency questionnaire intake by the foods' prebiotic content. Odds ratios (OR) and the corresponding 95% confidence intervals (CI) were derived by multiple logistic regression models. Nystose intake was marginally directly associated with breast (OR for the 4th versus the 1st quartile 1.20, 95% CI: 1.00-1.45), ovarian (OR 1.39, 95% CI: 1.04-1.84) and endometrial cancer risk (OR 1.32, 95% CI: 0.85-2.03). High 1F-β-fructofuranosylnystose intake was inversely associated with ovarian cancer (OR 0.67, 95% CI: 0.52-0.85). ITFs, kestose, raffinose and stachyose were not associated with the three cancers. The intake of most fiber-type prebiotics was not appreciably and consistently associated with breast, endometrial and ovarian cancer risks.

Use of an emulated trial to investigate the association between use of nitrogen-based bisphosphonates and risk of epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is the eighth most common cancer in women, with poor survival outcomes. Observational evidence suggests that nitrogen-based bisphosphonate (NBB) use may be associated with reduced risk of EOC, particularly the endometrioid and serous histotypes; however, confounding by indication is a concern. An alternative approach to investigate the chemo-preventive potential of NBBs is to emulate a target trial by identifying all women who initiate use of NBBs and investigate the risk of EOC for continued users compared with discontinued users. Using population-based linked data, we identified all Australian women aged over 50 years who first used NBBs over 2004-12. We used the year after first use to define treatment for each woman as either continued or discontinued use. We emulated randomization using stabilized inverse probability weights to balance the treatment groups using covariates including age, comorbidities and socioeconomic status. We followed women from treatment assignment until EOC diagnosis, death or 31 December 2013. We assessed the risk of EOC (overall and by histotype) using flexible parametric time-to-event models allowing for time-varying effects, and produced time-varying coefficients. Of the 313 383 women in the study, 472 were diagnosed with EOC during follow-up (261 serous EOC), with an average age at diagnosis of 72 years. Continued use of NBBs was associated with reduced risk of EOC overall (HR = 0.87, 95% CI: 0.69, 1.10), and serous EOC (HR = 0.71, 95% CI: 0.53, 0.96), compared with discontinued treatment, with estimates remaining constant over the 9-year follow-up. Results from our emulated trial suggest that in women who initiated NBB treatment, those who continued use had 13% and 29% lower hazards of being diagnosed with EOC overall and serous EOC, respectively, compared with women who discontinued use.

Recommendations of Health Care Professionals on the Issue of Breastfeeding in BRCA Carriers.

Purpose: Breastfeeding is associated with numerous short- and long-term neonatal and maternal health benefits. Specifically, in BRCA1/2 female carriers, breastfeeding has been shown to reduce the considerably increased risks of breast and ovarian cancer. Nevertheless, there is paucity of data referring to the recommended postpartum surveillance of BRCA1/2 carriers. The purpose of this study was to evaluate the recommendations of health professionals regarding breastfeeding in BRCA carriers. Methods: This cross-sectional survey was conducted using an anonymous questionnaire distributed through the "Good BRCA Genes-a support and information group for BRCA carriers" association. The questionnaire included Likert scale and open-ended questions, aimed to evaluate the performance of health professionals at various aspects of the recommended follow-up. Results: Of the 388 participants, 233 (60.0%) expressed dissatisfaction with explanations provided by health professionals regarding pregnancy and breastfeeding. Women reporting dissatisfaction with explanations were younger (36.8 ± 7.0 years) compared to those satisfied with the explanations (38.8 ± 7.6 years, p = 0.0081). No significant differences were noted between women satisfied and those dissatisfied with the explanations in terms of age of genetic diagnosis, origin, religion, geographic location, and the rates of personal or familial cancer history. Of the 175 responses to an open question "please describe the reasons for unsatisfactory explanation," 76.6% stated they received no explanation on the subject, whereas 5.4% described minimal explanation or conflicting recommendations. Surprisingly, 4.7% recalled being advised to avoid, stop, or limit breastfeeding. Discussion: The results of this survey emphasize the lack of knowledge of health professionals on the issue of breastfeeding in BRCA carriers. As genetic variants in these genes involve significant proportion of the population (up to 2.5% in Ashkenazi Jewish population), raising the awareness of health care personnel to the benefits of breastfeeding in these women seems prudent.

Opportunistic salpingectomy to decrease the risk of ovarian cancer.

Opportunistic salpingectomy to decrease the risk of ovarian cancer.

Diagnostic accuracy and clinical value of [68Ga]Ga-FAPI-46 PET/CT for staging patients with ovarian cancer: study protocol for a prospective clinical trial

Background[18F]Fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET) is recommended during diagnostic work-up for ovarian cancer; however, [18F]FDG PET has several inherent limitations. The novel oncologic PET-tracer fibroblast activation protein inhibitor (FAPI) has demonstrated promising results in multiple cancer types, including ovarian cancer, and could overcome the limitations of [18F]FDG PET; however, high-quality clinical studies are lacking. The primary objective of the present study is to compare the diagnostic accuracy of [68Ga]Ga-FAPI-46 PET/CT and [18F]FDG PET/CT in ovarian cancer patients and to investigate how this potential difference impacts staging and patient management.Methods and designFifty consecutive ovarian cancer patients will be recruited from Aalborg University Hospital, Denmark. This study will be a single-center, prospective, exploratory clinical trial that adheres to the standards for reporting diagnostic accuracy studies (STARD). This study will be conducted under continuous Good Clinical Practice monitoring. The eligibility criteria for patients are as follows: (1) biopsy verified newly diagnosed ovarian cancer or a high risk of ovarian cancer and referred for primary staging with [18F]FDG PET/CT; and (2) resectable disease, i.e., candidate for primary debulking surgery or neoadjuvant chemotherapy followed by interval debulking surgery. All recruited study subjects will undergo [68Ga]Ga-FAPI-46 PET/CT at primary staging, before primary debulking surgery or neoadjuvant chemotherapy (Group A + B), in addition to conventional imaging (including [18F]FDG PET/CT). Study subjects in Group B will undergo an additional [68Ga]Ga-FAPI-46 PET/CT following neoadjuvant chemotherapy prior to interval debulking surgery. The results of the study-related [68Ga]Ga-FAPI-46 PET/CTs will be blinded, and treatment allocation will be based on common clinical practice in accordance with current guidelines. The histopathology of surgical specimens will serve as a reference standard. A recruitment period of 2 years is estimated; the trial is currently recruiting.DiscussionTo our knowledge, this trial represents the largest, most extensive, and most meticulous prospective FAPI PET study conducted in patients with ovarian cancer thus far. This study aims to obtain a reliable estimation of the diagnostic accuracy of [68Ga]Ga-FAPI-46 PET/CT, shed light on the clinical importance of [68Ga]Ga-FAPI-46 PET/CT, and examine the potential applicability of [68Ga]Ga-FAPI-46 PET/CT for evaluating chemotherapy response.Trial registrationclinicaltrials.gov: NCT05903807, 2nd June 2023; and euclinicaltrials.eu EU CT Number: 2023-505938-98-00, authorized 11th September 2023.

Blood Iodine as a Potential Marker of the Risk of Cancer in BRCA1 Carriers.

Breast cancer and ovarian cancer pose a significant risk for BRCA1 carriers, with limited risk-reduction strategies. While improved screening helps in the early detection of breast cancer, preventive measures remain elusive. Emerging evidence suggests a potential link between iodine levels and modulation of cancer risk, but comprehensive studies are scarce. We conducted a prospective study among 989 BRCA1 carriers to assess the association between blood iodine levels and breast and ovarian cancer risk. Using inductively coupled plasma mass spectrometry, we measured blood iodine levels and observed a negative association with breast cancer risk, with a significantly lower risk observed in quartile 4 (iodine > 38.0 µg/L) compared with quartile 1 (iodine < 30 µg/L) (HR = 0.49; 95%CI: 0.27-0.87; p = 0.01). Conversely, a suggestive increase in ovarian cancer risk was observed at higher iodine levels (HR = 1.91; 95%CI: 0.64-5.67; p = 0.25). No significant association was found between iodine levels and overall cancer risk. Our results suggest the potential of iodine to reduce breast cancer risk in BRCA1 carriers after prophylactic oophorectomy but require further validation and investigation of its effect on ovarian cancer risk and overall mortality. These findings highlight the need for personalized strategies to manage cancer risk in BRCA1 carriers.

Unveiling the causal link between metabolic factors and ovarian cancer risk using Mendelian randomization analysis.

Metabolic abnormalities are closely tied to the development of ovarian cancer (OC), yet the relationship between anthropometric indicators as risk indicators for metabolic abnormalities and OC lacks consistency. The Mendelian randomization (MR) approach is a widely used methodology for determining causal relationships. Our study employed summary statistics from the genome-wide association studies (GWAS), and we used inverse variance weighting (IVW) together with MR-Egger and weighted median (WM) supplementary analyses to assess causal relationships between exposure and outcome. Furthermore, additional sensitivity studies, such as leave-one-out analyses and MR-PRESSO were used to assess the stability of the associations. The IVW findings demonstrated a causal associations between 10 metabolic factors and an increased risk of OC. Including "Basal metabolic rate" (OR= 1.24, P= 6.86×10-4); "Body fat percentage" (OR= 1.22, P= 8.20×10-3); "Hip circumference" (OR= 1.20, P= 5.92×10-4); "Trunk fat mass" (OR= 1.15, P= 1.03×10-2); "Trunk fat percentage" (OR= 1.25, P= 8.55×10-4); "Waist circumference" (OR= 1.23, P= 3.28×10-3); "Weight" (OR= 1.21, P= 9.82×10-4); "Whole body fat mass" (OR= 1.21, P= 4.90×10-4); "Whole body fat-free mass" (OR= 1.19, P= 4.11×10-3) and "Whole body water mass" (OR= 1.21, P= 1.85×10-3). Several metabolic markers linked to altered fat accumulation and distribution are significantly associated with an increased risk of OC.

Association of a polygenic risk score with risk of abnormal ultrasound findings and ovarian cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

10542 Background: Several susceptibility loci have been identified in genome-wide association studies (GWAS) of single nucleotide polymorphisms (SNPs) that are associated with ovarian cancers. Polygenic risk scores (PRS) combining certain loci have shown limited performance at predicting ovarian cancer risk. However, the utilization of PRS with ovarian cancer screening tests, like transvaginal ultrasound (TVU), warrants further evaluation. This study investigated the association between a polygenic risk score and ovarian cancer risk and abnormal TVU screening in a large-scale randomized controlled ovarian cancer screening trial. Methods: A polygenic risk score was constructed using weighted sums of risk alleles of 15 ovarian cancer SNPs identified in previous GWAS to evaluate the association with abnormal TVU screening results and ovarian cancer outcomes in female participants of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Complete genotyping information, TVU results, and ovarian cancer outcomes were available for 15722 females (mean age 62.2 years +/- 5.3) with European ancestry, including 116 ovarian cancer cases. Abnormal TVU was defined as ovarian volume or cyst volume &gt; 10 cm3, any solid/cystic component within a cystic ovarian tumor, or any solid area or papillary projection extending into the cavity of a cystic ovarian tumor. Polygenic risk scores were categorized as quartiles and odds ratios (OR) were calculated to assess risk of ovarian cancer or abnormal TVU result using the lowest PRS quartile as reference category. Results: TVU screening results were abnormal for 732 (732/15722, 4.66%) participants and normal for 14990 (14990/15722, 95.3%) participants at trial baseline. PRS within the fourth quartile demonstrated increased risk of ovarian cancer with reference to the lowest quartile (OR 1.77, 95% confidence interval: 1.04-3.08). Similarly, women in the highest quartile of the PRS had increased odds of an abnormal TVU screening result (OR 1.46, 95% confidence interval: 1.17-1.83) compared to women in the lowest PRS quartile. Conclusions: A polygenic risk score including 15 loci previously shown to be associated with ovarian cancer risk showed an association with increased ovarian cancer risk in the PLCO trial. Furthermore, the PRS was also associated with abnormal ultrasound results. Our findings support further evaluation of polygenic risk scores and transvaginal ultrasound for ovarian cancer risk stratification and screening approaches.

Impact of the oral contraceptive pill on the rate of ovarian cancer incidence in different races of women.

10521 Background: The rate of ovarian cancer incidence has drastically decreased over the years, though it is the fifth most leading cause of cancer death in women. Oral contraceptive pills (OCP) are a major cause for the decline due to decreasing the number of ovulations in a woman’s lifetime. In fact, women who have ever used OCPs have a 30-50% lower risk of ovarian cancer incidence compared to women who have never used OCP. This study compares the use of OCP in different races of women and its effect on the decline in incidence of ovarian cancer. Methods: The average rate of incidence per 100,000 cases per year for ovarian cancer in White, Asian and Black females was obtained from the National Program of Cancer Registries and Surveillance, Epidemiology, and End Results Program SEER*Stat Database: NPCR and SEER Incidence – U.S. Cancer Statistics 2001–2019 Public Use Research Database. The National Center for Health Statistics, National Survey of Family Growth was used to find ever use of OCP among sexually experienced women ages 15–49 in the United States for 2002 and 2015-2019. Results: White women, in the year 2002 and 2019 had a rate of ever OCP use of 87% and 87.5% respectively. During that same time period, they had the most drastic decrease in ovarian cancer incidence of 43%, compared to Black and Asian female population. In 2002, the incidence rate of ovarian cancer for White women was 14.6 per 100,000. 17 years later, in 2019, it dropped to 10.2 per 100,000. Black women had the second highest ever use of OCP and the second highest rate of change for ovarian cancer incidence. In 2002, 79.1% of Black women had ever used OCPs compared to 73% in 2019. In 17 years, the incidence rate per 100,00 decreased 39% for Black women. Incidence rate per 100,000 in 2002 was 10.4 and incidence rate in 2019 was 7.5 per 100,000. Asian women comparatively had the lowest ever use of OCP and the lowest rate of change for ovarian cancer incidence. Data was not available for 2002, but in 2019, Asian women’s ever use of OCP was 65.6%. Incidence of ovarian cancer for Asian women decreased by 21% between the years 2002 to 2019. Rate per 100,000 was 10.8 in 2002 and decreased to 8.9 per 100,000 in 2019. Conclusions: The oral contraceptive pill was made available in the year 1960. Since then, it has been a large factor as to why ovarian cancer incidence has declined. Healthcare disparities and cultural differences play a part in the rate of OCP use across different races of women. This, in turn, leads to varying levels of ovarian cancer incidence decline with White women having the highest rate, followed by Black, then Asian women. Ovarian cancer has a high mortality due to inadequate screening techniques and late diagnosis which is perpetuated by cultural barriers to receiving care. A decreased risk of ovarian cancer should be considered as a benefit when prescribing OCPs and a protective factor among all studied races.

Impact of insomnia on ovarian cancer risk and survival: a Mendelian randomization study

Insomnia is the most common sleep disorder in patients with epithelial ovarian cancer (EOC). We investigated the causal association between genetically predicted insomnia and EOC risk and survival through a two-sample Mendelian randomization (MR) study. Insomnia was proxied using genetic variants identified in a genome-wide association study (GWAS) meta-analysis of UK Biobank and 23andMe. Using genetic associations with EOC risk and overall survival from the Ovarian Cancer Association Consortium (OCAC) GWAS in 66,450 women (over 11,000 cases with clinical follow-up), we performed Iterative Mendelian Randomization and Pleiotropy (IMRP) analysis followed by a set of sensitivity analyses. Genetic associations with survival and response to treatment in ovarian cancer study of The Cancer Genome Atlas (TCGA) were estimated controlling for chemotherapy and clinical factors. Insomnia was associated with higher risk of endometrioid EOC (OR=1.60, 95% CI 1.05-2.45) and lower risk of high-grade serous EOC (HGSOC) and clear cell EOC (OR=0.79 and 0.48, 95% CI 0.63-1.00 and 0.27-0.86, respectively). In survival analysis, insomnia was associated with shorter survival of invasive EOC (OR=1.45, 95% CI 1.13-1.87) and HGSOC (OR=1.4, 95% CI 1.04-1.89), which was attenuated after adjustment for body mass index and reproductive age. Insomnia was associated with reduced survival in TCGA HGSOC cases who received standard chemotherapy (OR=2.48, 95% CI 1.13-5.42), but was attenuated after adjustment for clinical factors. This study supports the impact of insomnia on EOC risk and survival, suggesting treatments targeting insomnia could be pivotal for prevention and improving patient survival. National Institutes of Health, National Cancer Institute. Full funding details are provided in acknowledgments.

Genetic counseling and subsequent cascade genetic testing for women with a family history of pathogenic BRCA1 mutation: A cost-effectiveness model.

10621 Background: BRCA1 pathogenic mutations significantly increase the lifetime risk for breast and ovarian cancer, but risk reducing interventions such as bilateral salpingo-oophorectomy (RRBSO) and mastectomy (RRM) can improve outcomes. For women with a known family history of pathogenetic mutation, genetic counseling and testing is recommended. We sought to determine the cost-effectiveness (CE) of referral to genetic counseling with subsequent cascade testing. Methods: A decision analytic model was created using TreeAgePro 2023 software to evaluate the strategies of routine genetics consultation with Ambry panel testing versus no referral. It was assumed that known BRCA1 carriers would undergo annual breast cancer screening with mammogram and MRI at 25yo, RRBSO at 35yo, and RRM at 40yo. Non-carriers underwent routine annual mammogram at 40yo. Additionally, women who did not undergo genetic testing initially do so at the time of diagnosis of first cancer (breast of ovary) and subsequently underwent all recommended risk reducing strategies if found to have a pathogenic BRCA1 mutation. Outcomes included cost, quality adjusted life years (QALYs), ovarian and breast cancer cases and deaths. Univariate and multi-variate analyses were used to investigate the impact of the strategies. Results: In a Monte Carlo Microsimulation cohort of 10,000 women with a first degree relative with a pathogenic BRCA1 mutation, referral to genetic counseling with testing was the dominate strategy. This strategy resulted in a similar mean cost ($185,543 vs $185,171), but with 2,322 additional QALYs and incremental CE ratio (ICER) of 1,605 per QALY. This dominant strategy also resulted in 73 fewer ovarian cancer cases and 545 fewer breast cancer cases. Sensitivity analysis for the age of RRM was remarkable for an annual reduction in breast cancer cases by 97 cases and an annual cost savings of 375,658 for year prior to age 40 that mastectomy was performed. Conclusions: Routine genetic counseling and screening for all patients with a known family history of pathogenic BRCA1 mutation reduces breast and ovarian cancer diagnoses by prompting risk-reducing procedures without significant increase in cost when compared to diagnosis-based testing. Routine access to genetic counseling in a high-risk population would help inform earlier counseling and further decrease cancer risk, particularly as earlier RRM may improve outcomes. This is further supported by the low cost to implement. Improvement in identification and early referral could be targeted. [Table: see text]

The Associations and Causal Relationships of Ovarian Cancer - Construction of a Prediction Model.

To explore the risk and protective factors for developing ovarian cancer and construct a risk prediction model. Information related to patients diagnosed with ovarian cancer on the electronic medical record data platform of three tertiary hospitals in Guangdong Province from May 2018 to September 2023 was collected as the case group. Patients with non-ovarian cancer who attended the clinic during the same period were included in the control group. Logistic regression analysis was used to screen the independent variables and explore the factors associated with the development of ovarian cancer. An ovarian cancer risk prediction model was constructed using a decision tree C4.5 algorithm. The ROC and calibration curves were plotted, and the model was validated. Logistic regression analysis identified independent risk and protective factors for ovarian cancer. The sample size was divided into training and test sets in a ratio of 7:3 for model construction and validation. The AUC of the training and test sets of the decision tree model were 0.961 (95% CI:0.944-0.978) and 0.902 (95% CI:0.840-0.964), respectively, and the optimal cut-off values and their coordinates were 0.532 (0.091, 0.957), and 0.474 (0.159, 0.842) respectively. The accuracies of the training and test sets were 93.3% and 84.2%, respectively, and their sensitivities were 95.7% and 84.2%, respectively. The constructed ovarian cancer risk prediction model has good predictive ability, which is conducive to improving the efficiency of early warning of ovarian cancer in high-risk groups.

A targeted panel of actionable high-risk hereditary cancer predisposition genes to identify patients with pathogenic/likely pathogenic variants (PVs) irrespective of meeting established NCCN testing criteria.

10596 Background: Current germline cancer testing guidelines are limited to patients who meet specific personal and family cancer history (PH, FH) criteria. Our objective was to determine if differences in PV rates exist based on meeting National Comprehensive Cancer Network (NCCN) testing criteria in patients who underwent testing for known actionable genes. Methods: 29 genes with actionable NCCN management guidelines were evaluated. Consecutive patients (N=195,615) aged 18 to 100 years had hereditary cancer testing at a commercial laboratory at the ordering clinician’s discretion that included at least the 29 genes between June 2020 and August 2023. Per clinician-reported patient features (e.g. FH, PH, age), patients were categorized as meeting or not meeting current NCCN testing criteria for breast/ovarian/pancreatic (BOP v2.2024), and colorectal cancer (v1.2023). PV rates were calculated for all genes associated with breast, endometrial, ovarian, prostate, pancreatic, and colorectal cancer risk. Results: PVs were reported in 6634/105,194 (6.3%) patients that met the testing criteria and 5134/90,421 (5.7%) that did not. Of patients with a PV, 5134/11,768 (43.6%) did not meet NCCN testing criteria. When comparing patients with PVs based on NCCN testing criteria, patients were similar in age (median [Q1, Q3], 43.6 [35.0, 56.1] v 42.5 [34.7, 56.6] years) and sex (female 91.5% v 91.3%). While PH and FH were comparable, a PH of cancer (31.5% v 36.1%, OR=0.81, 95% CI 0.75-0.88, p&lt;0.001) and/or a FH of cancer (83.9% v 97.1%, OR=0.16, 95% CI [0.13-0.18], p&lt;0.001) were slightly lower in patients who did not meet criteria compared to those who met testing criteria. On evaluating results in genes associated with individual cancer types, similar PV rates between the groups were observed (Table). Among all patients with PVs, the most common genes were CHEK2, BRCA1, BRCA2, and ATM. Most patients had only 1 PV reported (met: 96.5%, not met: 97.5%). Conclusions: In this cohort of patients who underwent germline testing, approximately 40% of patients with PVs in this study did not meet existing NCCN testing criteria. PV rates were similar between patients that met criteria and those that did not. Broadening existing testing criteria may reduce the number of patients who would otherwise be missed, thereby allowing for treatment decision-making and cascade testing of family members. [Table: see text]

Incidental Serous Tubal Intraepithelial Carcinoma Finding in a Nepalese Patient Undergoing Opportunistic Salpingectomy and the Discovery of a BRCA1 Pathogenic Variant

BACKGROUND: Serous tubal intraepithelial carcinoma lesions are the precursor to high-grade serous ovarian carcinomas, which have the highest mortality rate among gynecologic malignancies. In women diagnosed with high-grade serous ovarian carcinoma, 20% of the carcinomas are found to be secondary to hereditary causes, with the majority being associated with germline pathogenic variants in BRCA1 and BRCA2 genes. Patients with a pathogenic variant are at high risk for developing high-grade serous ovarian carcinoma, so it is recommended that they undergo risk-reducing salpingo-oophorectomy in their 30s–40s. Opportunistic salpingectomy is the only ovarian cancer prevention method available for patients at average risk. Although serous tubal intraepithelial carcinoma lesions are rare in women at average risk, studies quote incidental serous tubal intraepithelial carcinoma lesion findings in 1–7% of patients undergoing opportunistic salpingectomy. CASE: A 38-year-old woman, gravida 2 para 2, of Nepalese ethnicity had an incidental finding of a serous tubal intraepithelial carcinoma lesion at the time of opportunistic salpingectomy for permanent sterilization at cesarean delivery. The serous tubal intraepithelial carcinoma lesion was found with representative sampling of the fallopian tubes because the patient was considered to be at average risk for ovarian cancer. This method is much less sensitive than the Sectioning and Extensively Examining the Fimbriated End (SEE-FIM) protocol, which is used with women known to be at high risk. This ultimately led to discovery of a BRCA1 mutation in the patient. CONCLUSION: The SEE-FIM protocol is used to identify serous tubal intraepithelial carcinoma lesions, but it is not routinely used on fallopian tubes of patients at average risk. Using the SEE-FIM protocol would lead to fewer missed serous tubal intraepithelial carcinoma lesions, but it is unclear how much extra cost and effort would be required to implement this protocol. There are knowledge gaps when it comes to understudied populations and hereditary breast and ovarian cancer gene prevalence. Studies show that current BRCA prediction models underestimate hereditary breast and ovarian cancer gene prevalence in Asian populations. Diagnosing serous tubal intraepithelial carcinoma lesions in understudied populations could lead to the discovery of a hereditary breast and ovarian cancer pathogenic variant that the patient may not have discovered until after a cancer diagnosis. Identification of a serous tubal intraepithelial carcinoma in a patient at average risk should lead to a referral for genetic counseling and screening.

61P Prognostic impact in ovarian cancer carriers of mutations located in cluster with higher risk of ovarian cancer in BRCA

61P Prognostic impact in ovarian cancer carriers of mutations located in cluster with higher risk of ovarian cancer in BRCA

Development and validation of radiomics nomogram for metastatic status of epithelial ovarian cancer

To develop and validate an enhanced CT-based radiomics nomogram for evaluating preoperative metastasis risk of epithelial ovarian cancer (EOC). One hundred and nine patients with histologically confirmed EOC were retrospectively enrolled. The volume of interest (VOI) was delineated in preoperative enhanced CT images, and 851 radiomics features were extracted. The radiomics features were selected by the least absolute shrinkage and selection operator (LASSO), and the rad-score was calculated using the formula of the radiomics label. A clinical model, radiomics model, and combined model were constructed using the logistic regression classification algorithm. Receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) were used to evaluate the diagnostic performance of the models. Seventy-five patients (68.8%) were histologically confirmed to have metastasis. Eleven optimal radiomics features were retained by the LASSO algorithm to develop the radiomic model. The combined model for evaluating metastasis of EOC achieved area under the curve (AUC) values of 0.929 (95% CI 0.8593–0.9996) in the training cohort and 0.909 (95% CI 0.7921–1.0000) in the test cohort. To facilitate clinical use, a radiomic nomogram was built by combining the clinical characteristics with rad-score. The DCA indicated that the nomogram had the most significant net benefit when the threshold probability exceeded 15%, surpassing the benefits of both the treat-all and treat-none strategies. Compared with clinical model and radiomics model, the radiomics nomogram has the best diagnostic performance in evaluating EOC metastasis. The nomogram is a useful and convenient tool for clinical doctors to develop personalized treatment plans for EOC patients.

Causal relationship between thyroid dysfunction and ovarian cancer: a two-sample Mendelian randomization study

PurposeObservational studies and clinical validation have suggested a link between thyroid dysfunction and an elevated ovarian cancer (OC) risk. However, whether this association indicates a cause-and-effect relationship remains uncertain. We aimed to investigate the plausible causal impact of thyroid dysfunction on OC through a Mendelian randomization (MR) study.MethodsGenome-wide association study (GWAS) data for thyrotropin (TSH), free thyroxine (FT4), hypothyroidism, and hyperthyroidism were obtained as exposures and those for OC (N = 199,741) were selected as outcomes. Inverse variance-weighted method was used as the main estimation method. A series of sensitivity analyses, including Cochran’s Q test, MR-Egger intercept analysis, forest plot scatter plot, and leave-one-out test, was conducted to assess the robustness of the estimates.ResultsGenetic prediction of hyperthyroidism was associated with a potential increase in OC risk (odds ratio = 1.094, 95% confidence interval: 1.029–1.164, p = 0.004). However, no evidence of causal effects of hypothyroidism, TSH, and FT4 on OC or reverse causality was detected. Sensitivity analyses demonstrated consistent and reliable results, with no significant estimates of heterogeneity or pleiotropy.ConclusionsThis study employed MR to establish a correlation between hyperthyroidism and OC risk. By genetically predicting OC risk in patients with hyperthyroidism, our research suggests new insights for early prevention and intervention of OC.

Effects of clinical covariates on serum miRNA expression among women without ovarian cancer.

Serum microRNAs (miRNAs) are potential biomarkers for ovarian cancer; however, many factors may influence miRNA expression. To understand potential confounders in miRNA analysis, we examined how sociodemographic factors and comorbidities, including known ovarian cancer risk factors, influence serum miRNA levels in women without ovarian cancer. Data from 1,576 women from the Mass General Brigham Biobank collected between 2012 and 2019, excluding subjects previously or subsequently diagnosed with ovarian cancer, were examined. Using a focused panel of 179 miRNA probes optimized for serum profiling, miRNA expression was measured by flow cytometry using the Abcam Fireplex® assay and correlated with subjects' electronic medical records. The study population broadly reflected the New England population. The median age of subjects was 49 years, 34% were current or prior smokers, 33% were obese (BMI >30kg/m2), 49% were postmenopausal, and 11% had undergone prior bilateral oophorectomy. Significant differences in miRNA expression were observed among ovarian risk factors such as age, obesity, menopause, BRCA1 or BRCA2 germline mutations or breast cancer in family history. Additionally, miRNA expression was significantly altered by prior bilateral oophorectomy, hypertension, and hypercholesterolemia. Other variables, such as smoking, parity, age at menarche, hormonal replacement therapy, oral contraception, breast, endometrial, or colon cancer, and diabetes were not associated with significant changes in the panel when corrected for multiple testing. Serum miRNA expression patterns are significantly affected by patient demographics, exposure history, and medical comorbidities. Understanding confounders in serum miRNA expression is important for refining clinical assays for cancer screening.

Current practices and challenges in genetic testing and counseling for women with breast and ovarian cancer in Asia.

This study assesses current practices and challenges in genetic testing and counseling (GT and C) for breast cancer gene (BRCA)1/2 mutations in Asia, considering the increased risk of ovarian cancer (OC) and breast cancer (BC) in women carrying these mutations. Insights were gathered through a questionnaire from breast surgeons, gynecologists, oncologists, and genetic clinicians in 10 Asian countries: Thailand, Hong Kong, South Korea, India, Vietnam, Malaysia, the Philippines, Taiwan, Singapore, and Indonesia. The questionnaire covered their knowledge, attitudes, and practices in GT and C for BRCA1/2 mutations, along with information on perceived gaps and unmet needs in the region. A total of 61 specialists participated in the survey. GT and C for BRCA1/2 mutations were less frequently offered in Asia compared to Western countries. Among the guidelines used, the National Comprehensive Cancer Network (NCCN) guidelines alone or in combination with other guidelines (American Society of Clinical Oncology [ASCO], National Institute for Health and Clinical Excellence [NICE], and European Society for Medical Oncology [ESMO]) were preferred for both BC and OC. Limited access to genetic counselors posed a significant challenge, resulting in delayed or no GT. Pretest genetic counseling was provided by the respondents themselves. Germline testing was preferred for BC, whereas both germline and somatic testing were preferred for OC, with the most preferred option being a multipanel germline test. Disparities exist in GT and C practices between Asian and Western countries. To address this, steps, such as patient and doctor education, increased accessibility and affordability of GT and C services, and improved infrastructure for identifying gene mutations, should be taken.

Racial and ethnic differences in epithelial ovarian cancer risk: an analysis from the Ovarian Cancer Association Consortium.

Limited estimates exist on risk factors for epithelial ovarian cancer (EOC) in Asian, Hispanic, and Native Hawaiian/Pacific Islander women. Participants in this study included 1734 Asian (n=785 case and 949 control participants), 266 Native Hawaiian/Pacific Islander (n=99 case and 167 control participants), 1149 Hispanic (n=505 case and 644 control participants), and 24 189 White (n=9981 case and 14 208 control participants) from 11 studies in the Ovarian Cancer Association Consortium. Logistic regression models estimated odds ratios (ORs) and 95% CIs for risk associations by race and ethnicity. Heterogeneity in EOC risk associations by race and ethnicity (P≤.02) was observed for oral contraceptive (OC) use, parity, tubal ligation, and smoking. We observed inverse associations with EOC risk for OC use and parity across all groups; associations were strongest in Native Hawaiian/Pacific Islander and Asian women. The inverse association for tubal ligation with risk was most pronounced for Native Hawaiian/Pacific Islander participants (odds ratio (OR)=0.25; 95% CI, 0.13-0.48) compared with Asian and White participants (OR=0.68 [95% CI, 0.51-0.90] and OR=0.78 [95% CI, 0.73-0.85], respectively). Differences in EOC risk factor associations were observed across racial and ethnic groups, which could be due, in part, to varying prevalence of EOC histotypes. Inclusion of greater diversity in future studies is essential to inform prevention strategies. This article is part of a Special Collection on Gynecological Cancers.