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Epithelial ovarian cancer (EOC) is the most lethal type of gynaecological cancer, due to lack of effective screening possibilities and because the disease tends to metastasize before onset of symptoms. Women with an increased inherited risk for EOC are advised to undergo a risk-reducing salpingo-oophorectomy (RRSO), which decreases their EOC risk by 96% when performed within guideline ages. However, it also induces premature menopause, which has harmful consequences. There is compelling evidence that the majority of EOCs originate in the fallopian tube. Therefore, a risk-reducing salpingectomy with delayed oophorectomy (RRS with DO) has gained interest as an alternative strategy. Previous studies have shown that this alternative strategy has a positive effect on menopause-related quality of life and sexual health when compared to the standard RRSO. It is hypothesized that the alternative strategy is non-inferior to the standard RRSO with respect to oncological safety (EOC incidence). Three prospective studies are currently including patients to compare the safety and/or quality of life of the two distinct strategies. In this article we discuss the background, opportunities, and challenges of the current and alternative strategy., (© 2024. The Author(s).)

The BRCA1/2 pathogenic variant (PV) increases the risk of breast and ovarian cancer; thus, risk-reducing salpingo-oophorectomy (RRSO) and mastectomy (RRM) are recommended. We evaluated the effects of the graphical display of cancer risk compared with those of numerical presentation on the decision-making for risk-reducing (RR) surgery. A total of 471 women representing the Korean population were recruited. The lifetime risk of breast/ovarian cancer were given numerically followed by graphically in hypothetical BRCA1/2 PV-positive cases. Subsequently, the study participants were asked for their willingness to undergo RRSO/RRM. When the ovarian cancer risk was shown as 44.0%, the percentage of study participants who chose RRSO was 41.0% after numerical presentation versus 39.9% after graphical display, of which the difference was not significant. When the breast cancer risk was presented as 72.0%, 30.4% of the participants opted for RRM under numerical presentation, whereas this increased to 38.6% under graphical display, of which the difference was significant (p < 0.0075). The average levels of the cancer risk which study participants consider RR surgery were 57.1% for ovarian cancer and 60.6% for breast cancer. This suggests that the impacts of different formats of risk communication on decision about RRSO or RRM may be different by the absolute levels of ovarian or breast cancer., (© 2024. The Author(s).)

Objective: Incisional hernias are a common complication of midline laparotomies. The aim of this study was to determine the impact of prophylactic mesh placement after midline laparotomy for ovarian tumors on the incidence of incisional hernia., Methods: We collected retrospective data from patients undergoing midline laparotomy for borderline or ovarian cancer with at least 12 months of follow-up, including those with and without mesh. Patient demographics, preoperative characteristics and risk factors for hernia were reported and grouped according to prophylactic mesh placement. A multivariate analysis was conducted to identify independent risk factors for incisional hernia. Kaplan-Meier curves illustrating the cumulative incidence of incisional hernia based on mesh placement were performed., Results: A total of 139 consecutive patients with available data were included, 58 in the non-mesh group and 81 in the mesh group, with high body mass index (BMI) as the most common reason for mesh placement. The mean (SD)) age was 60 years (13.97). A total of 11 patients (7.9%) had borderline tumors while 128 (92.1%) had invasive cancer. After clinical and radiological examination, 18.7% (26/139) of patients developed incisional hernia at a median follow-up of 35.8 months (IQR) 43.8): 31% (18/58) were detected in the non-mesh group, and 9.9% (8/81) in the mesh group (p<0.002). Multivariate analysis showed no-mesh placement (OR) 10; 95% CI) 2.8 to 35.919; p<0.001) as a significant risk factor for incisional hernia. Age ≥ 70 (OR 4.3; 95% CI 1.24 to 15; p=0.02) and BMI ≥ 29 (OR 4.4; 95% CI 1.27 to 14.93; p=0.019) were also identified as independent risk factors for hernia development. According to Kaplan-Meier curves, the cumulative incidence of incisional hernia was higher in the non-mesh group (p=0.002)., Conclusion: The incidence of incisional hernia was high in patients undergoing midline laparotomy for ovarian tumors. The addition of a prophylactic mesh may reduce this incidence, therefore there is a need to consider it as an option for high-risk patients, particularly those aged over 70 years or with a BMI ≥ 29 kg/m 2 ., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Women with pathogenic variants (PVs) in breast cancer (BC) and ovarian cancer (OC) associated genes are candidates for cancer risk-reducing strategies. Limited information is available regarding risk-reducing surgeries (RRS) among Hispanics. The aim of this study was to describe the uptake of RRS in an international real-world experience of Hispanic women referred for genetic cancer risk assessment (GCRA) and to identify factors affecting uptake., Methods: Between July 1997 and December 2019, Hispanic women, living in the United States or in Latin America, enrolled in the Clinical Cancer Genomics Community Research Network registry were prospectively included. Demographic characteristics and data regarding RRS were obtained from chart reviews and patient-reported follow-up questionnaires. Median follow-up was 41 months., Results: Among 1,736 Hispanic women referred for GCRA, 27.2% women underwent risk-reducing mastectomy (RRM), 25.5% risk-reducing salpingo-oophorectomy (RRSO) and, 10.7% both surgeries. Among BRCA carriers, rates of RRM and RRSO were 47.6% and 56.7%, respectively. In the multivariate analyses, being a carrier of a BC susceptibility gene (odds ratio [OR], 3.44), personal history of BC (OR, 6.22), living in the US (OR, 3.90), age ≤50 years (OR, 1.68) and, family history of BC (OR, 1.56) were associated with a higher likelihood of undergoing RRM. Carrying an OC susceptibility gene (OR, 6.72) was associated with a higher likelihood of undergoing RRSO., Conclusion: The rate of RRS among Hispanic women is suboptimal. PV carriers, women with personal history of cancer, and those with a family history of cancer were more likely to have RRS, with less uptake outside the US. Understanding personal and systemic factors influencing uptake may enable interventions to increase risk appropriate uptake of RRS.

Background: Cancer screening trials have required large sample sizes and long time-horizons to demonstrate cancer mortality reductions, the primary goal of cancer screening. We examine assumptions and potential power gains from exploiting information from testing control-arm specimens, which we call the "intended effect" (IE) analysis that we explain in detail herein. The IE analysis is particularly suited to tests that can be conducted on stored specimens in the control arm, such as stored blood for multicancer detection (MCD) tests., Methods: We simulated hypothetical MCD screening trials to compare power and sample size for the standard vs IE analysis. Under two assumptions that we detail herein, we projected the IE analysis for 3 existing screening trials (National Lung Screening Trial [NLST], Minnesota Colon Cancer Control Study [MINN-FOBT-A], and Prostate, Lung, Colorectal, Ovarian Cancer Screening Trial-colorectal component [PLCO-CRC])., Results: Compared with the standard analysis for the 3 existing trials, the IE design could have reduced cancer-specific mortality P values 6-fold (NLST), 33-fold (MINN-FOBT-A), or 260 000-fold (PLCO-CRC) or, alternately, reduced sample size (90% power) by 25% (NLST), 47% (MINN-FOBT-A), or 63% (PLCO-CRC). For potential MCD trial designs requiring 100 000 subjects per arm to achieve 90% power for multicancer mortality for the standard analysis, the IE analysis achieves 90% power for only 37 500-50 000 per arm, depending on assumptions concerning control-arm test-positives., Conclusions: Testing stored specimens in the control arm of screening trials to conduct the IE analysis could substantially increase power to reduce sample size or accelerate trials and could provide particularly strong power gains for MCD tests., (Published by Oxford University Press 2024.)

Introduction: Previous study results have been inconclusive, so this meta-analysis aims to evaluate the association between ovarian cancer and oral contraceptive pills (OCPs)., Methods: PubMed, EMBASE, Scopus, and Web of Science were searched to identify studies on the association between OCPs and ovarian cancer from January 1, 2000 through February 5, 2023. The pooled relative risk (RR) and odds ratio (OR) were used to measure this relationship., Results: A total of 67 studies were included. In the association between ever-use compared with never-use of OCPs and ovarian cancer risk, the pooled RR in cohort studies was 0.69 [95% CI: 0.61, 0.78]. For the relationship between duration of OCPs use and ovarian cancer in the cohort studies, no association between duration of use1-12 months 0.92 [95% CI: 0.82, 1.03] and duration of use 13-60 months 0.87 [95% CI: 0.73, 1.04], but there is a statistically significant inverse relationship between duration of use 61-120 months 0.62 [95% CI: 0.48, 0.81] and more than 120 months 0.51 [95% CI: 0.32, 0.80] and ovarian cancer. For the relationship between OCPs and histological subtype of epithelial ovarian cancer in the cohort studies, the pooled RR for invasive was 0.70 [95% CI: 0.56, 0.87], but no association between OCPs and borderline ovarian cancer 0.64 [95% CI: 0.31, 1.31]., Conclusion: Our analysis shows a statistically significant inverse relationship between ever-use compared to never-use of OCPs and ovarian cancer risk,and also between invasive cancer and OCPs. By increasing the duration of OCPs use, the risk of ovarian cancer decreased., (Copyright © 2024 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Objective: To describe extension of ovarian tissue beyond visible and National Comprehensive Cancer Network recommended margins among patients with BRCA mutations undergoing minimally invasive risk-reducing salpingo-oophorectomy., Methods: A prospective study of patients with BRCA mutations who underwent minimally invasive risk-reducing bilateral salpingo-oophorectomy was conducted. Patient enrollment occurred between October 2021 and 2023. Tissue specimens were analyzed according to the Sectioning and Extensively Examining the Fimbriated End protocol., Results: Twenty women with BRCA mutations were prospectively enrolled. All patients underwent minimally invasive surgery with 70% undergoing concurrent hysterectomy (n = 14). Approximately half of these procedures were performed with robotic assistance (n = 9, 45%). One patient was admitted overnight (5%); the other nineteen were discharged on the day of surgery (95%). One patient experienced a major complication and required readmission (5%). Extension of ovarian tissue beyond the visible ovary was noted on pathologic examination of six specimens (30%). In one patient this was observed on the left (17%), in three on the right (50%), and in two bilateral extension (33%) was noted. The distance ovarian stroma extended microscopically beyond the visible ovary was between 2 and 14 mm, with a median of 5 mm. Among patients with microscopic extension of ovarian tissue, the majority (n = 5, 83%) had a BRCA2 mutation., Conclusion: In women with BRCA mutations undergoing risk-reducing minimally invasive surgery, approximately one third had microscopic extension of ovarian stroma beyond the visible ovary. Current guidelines which recommend resection of at least 20 mm of tissue beyond the visible ovary are likely adequate in this population., Competing Interests: Declaration of competing interest The authors declare no potential conflicts of interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Dietary flavonoids may have potential effects on hormone-related cancers (HRCs) due to their anti-cancer properties via regulating hormones and suppressing inflammation and oxidative stress. We aimed to examine the association of flavonoid intake with risks of HRCs and whether this association was mediated by blood biomarkers involved in biological mechanisms., Methods: This prospective cohort study from UK Biobank included 187,350 participants free of cancer when the last dietary recall was completed. The dietary intakes of flavonoids and subclasses were assessed using 24-hour dietary recalls. Venous blood was collected at baseline and assayed for biomarkers of inflammation, hormones, and oxidative stress. Hazard ratios (HR) and 95 % confidential intervals (CI) for the associations between flavonoid intake and HRCs risk were estimated by the cause-specific Cox proportional hazards model. The role of blood biomarkers in the flavonoids-HRCs association was investigated through mediation analysis., Results: Over a median follow-up of 9.5 years, 3,392 female breast cancer, 417 ovarian cancer, 516 endometrial cancer, 4,305 prostate cancer, 45 testicular cancer, and 146 thyroid cancer cases were documented. Compared to the lowest quintile, multivariable-adjusted HRs (95 % CIs) in the highest quintile of total flavonoid intake were 0.89 (0.80-0.99) for breast cancer, 0.68 (0.50-0.92) for ovarian cancer, and 0.88 (0.80-0.98) for female-specific cancers. For subclasses, intakes of flavonols and anthocyanidins were inversely associated with the risk of female-specific cancers (P trend <0.05). Anthocyanidin intake was positively related to prostate cancer risk, whereas isoflavone intake was inversely linked to thyroid cancer risk (P trend <0.05). Additionally, certain biomarkers of inflammation, hormones and oxidative stress jointly mediated the association of flavonoid intake with the risk of female-specific cancers and prostate cancer., Conclusions: Our findings highlighted the importance of dietary flavonoids for the prevention of HRCs in the general population, providing epidemiological evidence for dietary guidelines., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Objective: Endogenous and exogenous hormonal factors have been associated with female breast, genital, and colorectal cancer risk. The aim of the present study is to conduct an evidence-based evaluation of the fraction of cancers attributable to and prevented by exogenous hormonal (i.e., combined oral contraceptives [COC] and combined estrogen-progestogen menopausal therapy [CEPMT]) and reproductive factors (i.e., parity and breastfeeding) in Italy., Study Design: We calculated the population attributable and prevented fractions combining relative risks and prevalence of exposure in Italian women. Italian cancer incidence and mortality data were extracted from national sources and used to estimate the number of cancer cases and deaths attributable to reproductive factors and exogenous hormones in Italy in 2020. For long-term effects, a 20-year latency period was considered., Results: COC were responsible for 4.4 % of breast and 10.9 % of cervical cancers in women aged 15-44, but also avoided 6.4 % of endometrial, 5.6 % of ovarian, and 2.9 % of colorectal cancers in women of all ages. Overall, COC use prevented 1174 cancer diagnoses and 577 cancer deaths. CEPMT caused 0.4 % of breast cancers at age 45-69. Low parity accounted for 8.1 %, 11.8 % and 15.5 % of breast, endometrial and ovarian cancers, respectively (6267 cases, 1796 deaths). Breastfeeding avoided 6.4 % of breast cancers (3775 cases, 897 deaths)., Conclusions: Our analysis quantified the complex effects of hormonal and reproductive factors on cancer burden in Italian women., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Epidemiological and observational studies suggest that vitamin D has potential for the chemoprevention of ovarian cancer. The anticancer effect of vitamin D in the fallopian tube epithelium (FTE), which is now thought to harbor the precursor cells for high grade ovarian cancer, is not known. The purpose of this study was to investigate whether vitamin D can inhibit carcinogenesis in the mogp-TAg fallopian tube (FT) ovarian cancer mouse model and examine underlying mechanisms. To test this hypothesis, 3 groups of 40 5-week-old female mogp-TAg mice were divided equally into two cohorts of 20 mice, treated with either vehicle (vitamin D solvent) or the active 1,25(OH)2D3 analogue EB1089, delivered via mini-pump or IP injection or cholecalciferol delivered in the feed. The FTs were characterized histologically and pathologically after 3 and 7 weeks of treatment. The effect of vitamin D on cultured human FTE cells was also examined. After 3 weeks, vitamin D, delivered as either cholecalciferol or EB1089 significantly inhibited FT carcinogenesis. After 7 weeks, cholecalciferol significantly reduced p53 signatures, serous tubal epithelial carcinoma, FT cancer, and plasma CA125 while increasing apoptosis in the FTE. EB1089 had no significant effect on FT carcinogenesis at 7 weeks. Cholecalciferol significantly reduced proliferation and increased apoptosis in vitro in p53-altered FTE cells. In conclusion, vitamin D inhibited FT carcinogenesis by clearing cells with p53 alterations. These data suggest that vitamin D has merit for the chemoprevention of fallopian tube/ovarian cancer. The optimal chemopreventive effect may be dependent on the route of vitamin D administration.

Purpose: To support doctors in counselling women with genetic predisposition for breast or gynecologic cancers on endocrine interventions., Methods: Evidence on the safety of endocrine interventions for fertility treatment, contraception, hormone replacement therapy after risk-reducing salpingo-oophorectomy (RRSO) or treatment of symptoms during peri- and postmenopause was analysed for carriers of probably pathogenic and pathogenic variants in BRCA1 or BRCA2 (BRCA1/2-pV), in other breast and ovarian cancer genes and the Lynch Syndrome. Cancer risks were compared with data on risks for the general population., Results: Data on risk modulation of endocrine interventions in women with genetic predisposition is limited. Ovarian hyperstimulation for fertility treatment may be performed. Oral contraceptives should not be used to reduce ovarian cancer risk in BRCA1/2-pV carriers. Premenopausal BRCA1/2-pV carriers and carriers of pV in Lynch Syndrome genes should be offered hormone replacement therapy (HRT) after RRSO, to prevent diseases caused by estrogen deficiency., Conclusion: Effect direction and strength of risk modulation by endocrine interventions is similar to the general population. Participation of individuals at risk in prospective registries is recommended., (© 2024. The Author(s).)

Importance: Population-based BRCA testing can identify many more BRCA carriers who will be missed by the current practice of BRCA testing based on family history (FH) and clinical criteria. These carriers can benefit from screening and prevention, potentially preventing many more breast and ovarian cancers and deaths than the current practice., Objective: To estimate the incremental lifetime health outcomes, costs, and cost-effectiveness associated with population-based BRCA testing compared with FH-based testing in Canada., Design, Setting, and Participants: For this economic evaluation, a Markov model was developed to compare the lifetime costs and outcomes of BRCA1/BRCA2 testing for all general population women aged 30 years compared with FH-based testing. BRCA carriers are offered risk-reducing salpingo-oophorectomy to reduce their ovarian cancer risk and magnetic resonance imaging (MRI) and mammography screening, medical prevention, and risk-reducing mastectomy to reduce their breast cancer risk. The analyses were conducted from both payer and societal perspectives. This study was conducted from October 1, 2022, to February 20, 2024., Main Outcomes and Measures: Outcomes of interest were ovarian cancer, breast cancer, additional heart disease deaths, and incremental cost-effectiveness ratio ICER per quality-adjusted life-year (QALY). One-way and probabilistic-sensitivity-analyses (PSA) were undertaken to explore the uncertainty., Results: In the simulated cohort of 1 000 000 women aged 30 years in Canada, the base case ICERs of population-based BRCA testing were CAD $32 276 (US $23 402.84) per QALY from the payer perspective or CAD $16 416 (US $11 903.00) per QALY from the societal perspective compared with FH-based testing, well below the established Canadian cost-effectiveness thresholds. Population testing remained cost-effective for ages 40 to 60 years but not at age 70 years. The results were robust for multiple scenarios, 1-way sensitivity, and PSA. More than 99% of simulations from payer and societal perspectives were cost-effective on PSA (5000 simulations) at the CAD $50 000 (US $36 254.25) per QALY willingness-to-pay threshold. Population-based BRCA testing could potentially prevent an additional 2555 breast cancers and 485 ovarian cancers in the Canadian population, corresponding to averting 196 breast cancer deaths and 163 ovarian cancer deaths per 1 000 000 population., Conclusions and Relevance: In this economic evaluation, population-based BRCA testing was cost-effective compared with FH-based testing in Canada from payer and societal perspectives. These findings suggest that changing the genetic testing paradigm to population-based testing could prevent thousands of breast and ovarian cancers.

Background: Improved technologies paired with an increase in access to genetic testing have led to the availability of expanded carrier screening evaluating hundreds of disorders. Currently, most autosomal dominant mutations, such as BRCA1, are not included in expanded carrier assays. Screening pregnant or preconception reproductive-aged women for BRCA1 may present a unique opportunity to perform population-based screening for patients at a time when precancer screening, chemoprevention, and/or risk-reducing surgery may be beneficial., Objective: This study aimed to inform clinical decision-making as to whether the universal incorporation of BRCA1 testing at the time of obstetrical prenatal carrier screening is cost-effective., Study Design: A decision analysis and Markov model was created. The initial decision point in the model was BRCA1 testing at the time of expanded carrier screening. Model probabilities, cost, and utility values were derived from published literature. For BRCA1-positive patients, the model simulated breast cancer screening and risk-reducing surgical interventions. A cycle length of 1 year and a time horizon of 47 years were used to simulate the lifespan of patients. The setting was obstetrical clinics in the United States, and the participants were a theoretical cohort of 1,429,074 pregnant patients who annually underwent expanded carrier screening., Results: Among our cohort, BRCA1 testing resulted in the identification of an additional 3716 BRCA1-positive patients, the prevention of 1394 breast and ovarian cancer cases, and 1084 fewer deaths. BRCA1 testing was a cost-effective strategy compared with no BRCA1 testing with an incremental cost-effectiveness ratio of $86,001 per quality-adjusted life years. In a 1-way sensitivity analysis, we varied the prevalence of BRCA1 in the population from 0.00% to 20.00% and found that BRCA1 testing continued to be the cost-effective strategy until the prevalence rate was reduced to 0.16%. Multiple additional sensitivity analyses did not substantially affect the cost-effectiveness., Conclusion: The addition of BRCA1 testing to obstetrical prenatal carrier screening is a cost-effective management strategy to identify at-risk women at a time when cancer screening and preventive strategies can be effective. Despite the burden of additional genetic counseling, prenatal care represents a unique opportunity to implement population-based genetic testing., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Raloxifene and bazedoxifene are selective estrogen receptor modulators (SERMs) used to prevent and treat osteoporosis in postmenopausal women. Raloxifene is also known for its preventive effect against invasive breast cancer; however, its effect on other cancer types is unclear. This study investigated the incidence of various cancers in osteoporosis patients receiving SERM therapy to determine its association with the risk of developing specific cancer types., Methods: This retrospective cohort study examined the association between SERM use and the incidence of cervical, endometrial, ovarian, and colorectal cancers in postmenopausal women using data from the Korean National Health Insurance Service. Propensity score matching ensured group comparability by analyzing 95,513 participants. Cox proportional hazard models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) to assess the cancer risk associated with SERM therapy, differentiating between the effects of raloxifene and bazedoxifene., Results: SERM therapy was associated with a reduced risk of cervical (adjusted HR = 0.47, 95% CI = 0.31-0.71), ovarian (adjusted HR = 0.61, 95% CI = 0.42-0.88), and colorectal cancer (adjusted HR = 0.49, 95% CI = 0.42-0.57). No significant risk reduction was observed for endometrial cancer (adjusted HR = 1.05, 95% CI = 0.70-1.59). A comparison between raloxifene and bazedoxifene revealed no significant differences in their cancer prevention effects., Conclusion: SERM therapy administration is associated with a decreased incidence of cervical, ovarian, and colorectal cancers. Notably, the effects of raloxifene and bazedoxifene were consistent. Further investigations are crucial to elucidate the mechanisms underlying these observations and their clinical implications.

Lynch syndrome (LS) is an autosomal dominant genetic disorder that results in an increased risk of ovarian and endometrial cancers. The aim of this paper was to explore the management of this risk through screening and prevention. Published materials and evidence were explored and summarized. This paper demonstrated that while there has been increased awareness and advances in the identification and diagnosis of patients with LS, recommendations for screening and prevention remain less evidence-based. In decisions of management of patients with LS, a shared decision-making model should be used considering individual patient goals., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Hereditary cancer syndromes (HCS) are responsible for up to 10% of all cancers. At present, the majority of cancer susceptibility testing is initiated after a cancer diagnosis. There exists a significant opportunity for primary care providers including general obstetrician-gynecologists to engage in hereditary cancer risk assessment through adequate family history evaluation, initiation of genetic testing, and following the recommendations of national organizations. Identifying hereditary cancer genes may prompt primary prevention efforts such as enhanced screening, prevention, or personalized care strategies. We will review the literature regarding the approach and assessment of the most common gynecologic HCS., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Due to improved understanding of ovarian cancer pathogenesis, we have an unprecedented chance to decrease the burden of disease by maximizing opportunities for prevention. Innovations in surgical options for prevention stem from the discovery that many cases directly or indirectly arise from the fallopian tube. Surgical prevention with salpingectomy alone decreases risk by ≥50%. Effective hormonal and nonhormonal chemopreventive agents are also available. Risk stratification is key to ensuring that options for prevention are appropriately matched to individual risk profile. This evidence-based review provides a critical appraisal of the translational health research endeavors supporting ovarian cancer prevention in clinical practice., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Established personal and familial risk factors contribute collectively to a woman's risk of breast or ovarian cancer. Existing clinical services offer genetic testing for pathogenic variants in high-risk genes to investigate these risks but recent information on the role of common genomic variants, in the form of a Polygenic Risk Score (PRS), has provided the potential to further personalise breast and ovarian cancer risk assessment. Data from cohort studies support the potential of an integrated risk assessment to improve targeted risk management but experience of this approach in clinical practice is limited., Methods and Analysis: The polygenic risk modification trial is an Australian multicentre prospective randomised controlled trial of integrated risk assessment including personal and family risk factors with inclusion of breast and ovarian PRS vs standard care. The study will enrol women, unaffected by cancer, undergoing predictive testing at a familial cancer clinic for a pathogenic variant in a known breast cancer (BC) or ovarian cancer (OC) predisposition gene ( BRCA1 , BRCA2 , PALB2 , CHEK2 , ATM , RAD51C , RAD51D ). Array-based genotyping will be used to generate breast cancer (313 SNP) and ovarian cancer (36 SNP) PRS. A suite of materials has been developed for the trial including an online portal for patient consent and questionnaires, and a clinician education programme to train healthcare providers in the use of integrated risk assessment. Long-term follow-up will evaluate differences in the assessed risk and management advice, patient risk management intentions and adherence, patient-reported experience and outcomes, and the health service implications of personalised risk assessment., Ethics and Dissemination: This study has been approved by the Human Research Ethics Committee of Peter MacCallum Cancer Centre and at all participating centres. Study findings will be disseminated via peer-reviewed publications and conference presentations, and directly to participants., Trial Registration Number: ACTRN12621000009819., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Objective: The majority of high-grade serous carcinomas (HGSC) of the ovary, fallopian tube, and peritoneum arise from the precursor lesion called serous tubal intraepithelial carcinoma (STIC). It has been postulated that cells from STICs exfoliate into the peritoneal cavity and give rise to peritoneal HGSC several years later. While co-existent STICs and HGSCs have been reported to share similarities in their mutational profiles, clonal relationship between temporally distant STICs and HGSCs have been infrequently studied and the natural history of STICs remains poorly understood., Methods: We performed focused searches in two national databases from the Netherlands and identified a series of BRCA1/2 germline pathogenic variant (GPV) carriers (n = 7) who had STIC, and no detectable invasive carcinoma, at the time of their risk-reducing salpingo-oophorectomy (RRSO), and later developed peritoneal HGSC. The clonal relationship between these STICs and HGSCs was investigated by comparing their genetic mutational profile by performing next-generation targeted sequencing., Results: Identical pathogenic mutations and loss of heterozygosity of TP53 were identified in the STICs and HGSCs of five of the seven patients (71%), confirming the clonal relationship of the lesions. Median interval for developing HGSC after RRSO was 59 months (range: 24-118 months)., Conclusion: Our results indicate that cells from STIC can shed into the peritoneal cavity and give rise to HGSC after long lag periods in BRCA1/2 GPV carriers, and argues in favor of the hypothesis that STIC lesions may metastasize., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Ovarian cancer is an aggressive malignancy and the leading cause of death among gynecologic cancers. Researchers have evaluated prophylactic medications that potentially avert the manifestation of ovarian cancer, but currently, there are no reliable screening measures for this disease. Nevertheless, the largest study involving aspirin use and ovarian cancer reported a substantive risk reduction from enduring aspirin use. Since there are countervailing data to impugn the potential benefits of aspirin use in staving off ovarian cancer, further research should scrutinize the use of this medication as a prophylactic intervention, especially in women who are at higher risk for developing the disease.

Background: Cancer screening trials have required large sample sizes and long time-horizons to demonstrate cancer mortality reductions, the primary goal of cancer screening. We examine assumptions and potential power gains from exploiting information from testing control-arm specimens, which we call the "intended effect" (IE) analysis that we explain in detail herein. The IE analysis is particularly suited to tests that can be conducted on stored specimens in the control arm, such as stored blood for multicancer detection (MCD) tests., Methods: We simulated hypothetical MCD screening trials to compare power and sample size for the standard vs IE analysis. Under two assumptions that we detail herein, we projected the IE analysis for 3 existing screening trials (National Lung Screening Trial [NLST], Minnesota Colon Cancer Control Study [MINN-FOBT-A], and Prostate, Lung, Colorectal, Ovarian Cancer Screening Trial-colorectal component [PLCO-CRC])., Results: Compared with the standard analysis for the 3 existing trials, the IE design could have reduced cancer-specific mortality P values 5-fold (NLST), 33-fold (MINN-FOBT-A), or 14 160-fold (PLCO-CRC) or, alternately, reduced sample size (90% power) by 26% (NLST), 48% (MINN-FOBT-A), or 59% (PLCO-CRC). For potential MCD trial designs requiring 100 000 subjects per arm to achieve 90% power for multicancer mortality for the standard analysis, the IE analysis achieves 90% power for only 37 500-50 000 per arm, depending on assumptions concerning control-arm test-positives., Conclusions: Testing stored specimens in the control arm of screening trials to conduct the IE analysis could substantially increase power to reduce sample size or accelerate trials and could provide particularly strong power gains for MCD tests., (Published by Oxford University Press 2024.)

Reproductive cancers, encompassing various malignancies like endometrial, ovarian, cervical cancer, and gestational trophoblastic neoplasia, pose a significant global health burden. Understanding their patterns is vital for effective prevention and management. Contraceptives show a protective effect against some of these cancers. This clinical guidance document aims to elucidate the disease burden of reproductive cancers and the evidence supporting contraceptive methods in prevention and management. Regional disparities in incidence and mortality highlight the urgent need for targeted interventions, particularly in low-resource settings. Healthcare providers must weigh individual risk profiles and medical eligibility criteria when discussing contraceptive options. Enhanced health literacy through direct patient education is essential for leveraging low-cost behavioral interventions to mitigate reproductive cancer risks., (© 2024 International Federation of Gynecology and Obstetrics.)

Purpose: Carriers of pathogenic variants in BRCA1/2 have an elevated lifetime cancer risk warranting high-risk screening and risk-reducing procedures for early detection and prevention. We report on prevention practices among women with pathogenic BRCA variants in order to document follow through with NCCN recommendations and to identify barriers to guideline-recommended care., Methods: Our cohort included women who had genetic testing through a cancer genetic clinic and completed a 54-item questionnaire to measure socio-demographics, medical history, rates of cancer screening and risk-reducing surgery, disclosure of test results, and cancer worry. Outcomes included rates of completion of risk-reducing salpingo-oophorectomy (RRSO), risk-reducing mastectomy (RRM), and NCCN risk-reducing and age-dependent screening guidelines (version 3.2019). Multivariable logistic regression analyses were used to evaluate potential predictors of these outcomes., Results: Of 129 evaluable women with pathogenic BRCA1/2 variants, 95 (74%) underwent RRSO and 77 (60%) had RRM, respectively, and 107 (83%) were considered adherent to NCCN guidelines. Women with a history of breast or ovarian cancer were more likely to have RRM (OR = 4.38; 95% CI 1.80-11.51; p = 0.002). Increasing age was associated with an increased likelihood of RRSO (OR = 1.05; 95% CI 1.01-1.09; p = 0.019) and decreased likelihood for RRM (OR = 0.95; 95% CI 0.92-0.99; p = 0.013). Women who had RRM were 3 times more likely to undergo RRSO (OR = 2.81; 95% CI 1.10-7.44; p = 0.025). Women who had genetic testing after June 2013 were less likely to have RRM than those tested before June 2013 (OR = 0.42; 95% CI 0.18-0.95; p = 0.040. None of the other measured factors were associated with rates of RRSO, RRM or follow through with NCCN recommendations. There was near universal (127/129) reported disclosure of genetic test results to family members, resulting in the discovery of a median of 1 relative with a pathogenic variant (range = 0-8)., Conclusion: An evaluation of follow up practice in a cohort of women with pathogenic variants in BRCA1/2 revealed high rates of reported completion of screening and surgical risk-reducing recommendations. Educational efforts should continue to reinforce the importance of follow-through with guideline recommended care among this high-risk group., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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.

Objectives: To assess the association of socioeconomic demographics with recommendation for and uptake of risk-reducing bilateral salpingo-oophorectomy (rrBSO) in patients with BRCA1 and BRCA2 ( BRCA1/2 ) mutations., Design: Retrospective cohort, semistructured qualitative interviews., Setting and Participants: BRCA1/ 2 mutation carriers at an urban, public hospital with a racially and socioeconomically diverse population., Intervention: None., Primary and Secondary Outcomes: The primary outcomes were rate of rrBSO recommendation and completion. Secondary outcomes were sociodemographic variables associated with rrBSO completion., Results: The cohort included 167 patients with BRCA1/2 mutations of whom 39% identified as black (n=65), 35% white (n=59) and 19% Hispanic (n=32). Over 95% (n=159) received the recommendation for age-appropriate rrBSO, and 52% (n=87) underwent rrBSO. Women who completed rrBSO were older in univariable analysis (p=0.05), but not in multivariable analysis. Completion of rrBSO was associated with residence in zip codes with lower unemployment and documented recommendation for rrBSO (p<0.05). All subjects who still received care in the health system (n=79) were invited to complete interviews regarding rrBSO decision-making, but only four completed surveys for a response rate of 5.1%. Themes that emerged included menopause, emotional impact and familial support., Conclusions: In this understudied population, genetic counselling and surrogates of financial health were associated with rrBSO uptake, highlighting genetics referrals and addressing social determinants of health as opportunities to improve cancer prevention and reduce health inequities. Our study demonstrates a need for more culturally centred recruiting methods for qualitative research in marginalised communities to ensure adequate representation in the literature regarding rrBSO., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Estrogen plays a crucial role in ovarian tumorigenesis. Phytoestrogens (PEs) are a type of daily dietary nutrient for humans and possess a mild estrogenic characteristic. This study aimed to assess the correlation of the consumption of dietary PEs with ovarian cancer risk using data in the prostate, lung, colorectal and ovarian (PLCO) cancer screening trial. Participants were enrolled in PLCO from 1993 to 2001. Hazard ratios (HR) and 95% confidence intervals (CI) were utilized to determine the association between the intake of PEs and ovarian cancer occurrence, which were calculated by the Cox proportional hazards regression analysis. In total, 24 875 participants were identified upon completion of the initial dietary questionnaire (DQX). Furthermore, the analysis also included a total of 45 472 women who filled out the diet history questionnaire (DHQ). Overall, after adjustment for confounders, the dietary intake of total PEs was significantly associated with the risk of ovarian cancer in the DHQ group (HRQ4vsQ1 = 0.69, 95% CI: 0.50-0.95; P for trend = 0.066). Especially, individuals who consumed the highest quartile of isoflavones were found to have a decreased risk of ovarian cancer in the DHQ group (HRQ4vsQ1 = 0.68, 95% CI: 0.50-0.94; P for trend = 0.032). However, no such significant associations were observed for the DQX group. In summary, this study suggests that increased dietary intake of total PEs especially isoflavones was linked with a lower risk for developing ovarian cancer. More research is necessary to validate the findings and explore the potential mechanisms., (© The Author(s) 2024. Published by Oxford University Press.)

Competing Interests: Competing interests:: None declared.

Ovarian cancer is the seventh most common cancer in women in the world, with an estimated worldwide mortality of over 207'000 women every year. This cancer, due to the current lack of adequate screening techniques, is commonly diagnosed late and has a poor prognosis. The oral contraceptive pill is considered the most effective prevention strategy for ovarian cancer in the general population, being associated with a decreased incidence while also having a substantial positive impact on the mortality rate, which is reduced by up to 50%. BRCA1 and BRCA2 germline mutated women have an augmented risk of ovary and breast cancer: despite international guidelines that consider prophylactic surgery as the gold standard for ovarian cancer prevention, there are currently no effective non-invasive preventive methods. In BRCA1\2 mutated patients, clinicians should weigh the benefits of contraceptive pills against the risk of long-term thromboembolic side effects and hormonal malignancies such as breast and cervical cancer. A multidisciplinary team should counsel patients on the most appropriate risk-reduction strategy tailored to their needs and expectations, proposing the oral contraceptive pill to selected patients after balancing the risks of adverse effects and the benefits on both contraception and chemoprevention., (© 2023. The Author(s), under exclusive licence to Hellenic Endocrine Society.)

The Precision Medicine Initiative was launched upon the potential of genomic information to tailor medical care. Cascade genetic testing represents a powerful application of precision medicine and involves the process of familial diffusion or the "cascade" of genomic risk information. When an individual (proband) is found to carry a cancer-associated germline pathogenic mutation, the information should be cascaded or shared with at-risk relatives. First degree relatives have a 50% likelihood of carrying the same cancer-associated mutation. This process of cascade testing offers at-risk relatives the opportunity for genetic testing and, for those who also carry the cancer-associated mutation, genetically targeted primary disease prevention through intensive cancer surveillance, chemoprevention and risk-reducing surgery, reducing morbidity and preventing mortality. Cascade testing has been designated by the Centers for Disease Control and Prevention as a Tier 1 genomic application for hereditary breast and ovarian cancer. In this manuscript we describe a cascade genetic testing and in particular focus on its potential to provide necessary care to medically underserved and vulnerable populations., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Being a gynecologic oncologist is a privilege. Women with cancer address their challenges with grit and resilience. Their most basic questions motivated my career-long search for scientific answers hidden in genetics, novel therapeutics, and cancer prevention. But medicine is a team sport. Working alongside gifted colleagues and mentoring trainees to assume starring roles on the team has sustained and enriched my career. Advocating for patients and the specialty of gynecologic oncology provided another means to advance research and cancer awareness to improve patient outcomes. The author believe the most exciting times are yet to come., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Healthy carriers of BRCA1/2 pathogenic variants (PVs) may benefit from risk-reducing measures of proven efficacy. The main approach to identify these individuals is cascade testing, and strategies to support this complex process are under investigation. In Italy, cascade testing has received little attention; therefore, we analyzed the uptake and characteristics of BRCA1/2 cascade testing in families diagnosed with HBOC between 2017 and 2019 at two Italian genetics centers. All blood relatives aged 18 years or older at September 2022 and who could be involved in the first step of cascade testing (i.e., all the living relatives closest to the proband) were included. In addition to first-degree relatives, individuals who were second-, third- or fourth-degree relatives were included if the closest relative(s) was/were deceased. Overall, 213 families were included (103, Genoa; 110, Bologna). Most probands were women affected by breast and/or ovarian cancer (86.4%, Genoa; 84.5%, Bologna), and the branch segregating the PV was known/suspected in 62% of families (62.1%, Genoa; 60.9%, Bologna). Overall, the uptake of cascade testing was 22.8% (25.8%, Genoa; 19.9%, Bologna; OR = 0.59: 95%CI 0.43-0.82). It was strongly associated with female gender (OR = 3.31, 95%CI 2.38-4.59), age ≤ 70 years (< 30 years OR = 3.48, 95%CI 1.85-6.56; 30-70 years OR = 3.08, 95%CI 2.01-4.71), first-degree relationship with the proband (OR = 16.61, 95%CI 10.50-26.28) and segregation of the PV in both the maternal (OR = 2.54, 95%CI 1.72-3.75) and the paternal branch (OR = 4.62, 95%CI 3.09-6.91). These real-world data may be important to inform the design and implementation of strategies aimed at improving the uptake of HBOC cascade testing in Italy., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

More attention has been paid to immunotherapy for ovarian cancer and the development of tumor vaccines. We developed a trichostatin A (TSA)-modified tumor vaccine with potent immunomodulating activities that can inhibit the growth of ovarian cancer in rats and stimulate immune cell response in vivo. TSA-treated Nutu-19 cells inactivated by X-ray radiation were used as a tumor vaccine in rat ovarian cancer models. Prophylactic and therapeutic experiments were performed with TSA-modified tumor vaccine in rats. Flow cytometry and ELISpot assays were conducted to assess immune response. Immune cell expression in the spleen and thymus were detected by immunohistochemical staining. GM-CSF, IL-7, IL-17, LIF, LIX, KC, MCP-1, MIP-2, M-CSF, IP-10/CXCL10, MIG/CXCL9, RANTES, IL-4, IFN-γ, and VEGF expressions were detected with Milliplex Map Magnetic Bead Panel immunoassay. TSA vaccination in therapeutic and prophylactic models could effectively stimulate innate immunity and boost the adaptive humoral and cell-mediated immune responses to inhibit the growth and tumorigenesis of ovarian cancer. This vaccine stimulated the thymus into reactivating status and enhanced infiltrating lymphocytes in tumor-bearing rats. The expression of key immunoregulatory factors were upregulated in the vaccine group. The intensities of infiltrating CD4+ and CD8+ T cells and NK cells were significantly increased in the vaccine group compared to the control group (P<0.05). This protection was mainly dependent on the IFN-γ pathway and, to a much lesser extent, by the IL-4 pathway. The tumor cells only irradiated by X-ray as the control group still showed a slight immune effect, indicating that irradiated cells may also cause certain immune antigen exposure, but the efficacy was not as significant as that of the TSA-modified tumor vaccine. Our study revealed the potential application of the TSA-modified tumor vaccine as a novel tumor vaccine against tumor refractoriness and growth. These findings offer a better understanding of the immunomodulatory effects of the vaccine against latent tumorigenesis and progression. This tumor vaccine therapy may increase antigen exposure, synergistically activate the immune system, and ultimately improve remission rates. A vaccine strategy designed to induce effective tumor immune response is being considered for cancer immunotherapy.

Objective: To determine the utilization of risk-reducing strategies and screening protocols for ovarian cancer in female BRCA1/2 carriers. Methods: This study was a sub-analysis of female participants from a larger multicenter, cross-sectional survey of BRCA1/2 mutation carriers unaffected by cancer. The questionnaire was administered electronically via email at four institutions located in the northeast United States. Data were analyzed with Fisher's exact test. Results: The survey was completed by 104 female BRCA mutation carriers. BRCA subtypes included 54.3% BRCA2 , 41.0% BRCA1 , and 2.9% both. The age at which patients underwent genetic testing varied 21.2% were 18-24 years, 25.0% were 25-34 years, 29.8% were 35-44 years, and 24.0% were 45 years or older. Nearly, all respondents (97.1%) reported that a provider had discussed risk-reducing surgeries. Of the 79 females who underwent genetic testing before 45 years of age, 53.2% reported that a health care provider recommended taking combined oral contraceptive pills (COCs) to reduce their risk of ovarian cancer, and, of these women, 88.1% chose to use them. COCs were offered at higher rates among women who were younger at the age of genetic testing (18-24: 86%, 25-34: 62%, 35-44: 23%; p < 0.0001). Approximately half (55.8%) of the respondents reported having been offered increased screening for possible early detection of ovarian cancer, of which 81.0% chose to undergo screening. The majority utilized a combination of transvaginal ultrasound and serum CA125 measurements. There were no differences observed in screening utilization based on BRCA mutation type. Conclusion: In our cohort of female BRCA mutation carriers, risk-reducing surgery was offered to almost all women, whereas only half were offered risk-reducing medication and/or increased screening. Further investigation is needed to identify barriers to the utilization of risk-reducing strategies among this high-risk population.

Purpose: Early diagnosis of ovarian cancer (OC) increases survival rates; however, due to low awareness levels, women may be diagnosed with OC at the advanced stage. The aim of this cross-sectional study is to reveal the OC awareness of Turkish women and affecting factors., Methods: Participants were invited to study via social media tools between February-June 2022. Data was collected with Personal Information Form and the "OC Awareness Scale" from 446 women., Results: 81% of the participants did not recall OC symptoms, 80.8% recognized OC risk factors. The most frequently recalled and recognized OC symptom is pelvic pain (19.8%; 55.8%, respectively). The most frequently recalled and recognized OC risk factors were smoking (43.1%, 67.9%, respectively) and family history (39%, 58.7%, respectively). 2% of the participants felt very confident in recognizing the signs, 72.9% would seek help within 1-2 days when they recognized the signs of OC., Conclusions: The awareness of OC was higher among women who had advanced age, higher education, family history and were in menopause. Turkish women have low level of awareness and knowledge about OC symptoms and risk factors. There is an urgent need for an OC awareness campaign that takes into account the socio-demographic characteristics of women. The results of the study may also guide strategies to prevent OC., (© 2024 The Authors. Public Health Nursing published by Wiley Periodicals LLC.)

Purpose: The U.S. Preventive Services Task Force recommends screening women to identify individuals eligible for genetic counseling based on a priori hereditary breast and ovarian cancer syndrome (HBOC) risk (i.e., risk assessment). However, risk assessment has not been widely integrated into primary care. This qualitative study explored young women's views on implementing routine HBOC risk assessment with a focus on equity and patient-centeredness., Methods: We conducted group discussions with young women (aged 21-40 years) receiving care in an integrated health care system. Discussion groups occurred in two phases and used a modified deliberative approach that included a didactic component and prioritized developing consensus. Twenty women participated in one of three initial small group discussions (phase one). All 20 were invited to participate in a subsequent large group discussion (phase two), and 15 of them attended., Findings: Key themes and recommendations were as follows. Risk assessment should be accessible, contextualized, and destigmatized to encourage participation and reduce anxiety, particularly for women who do not know their family history. Providers conducting risk assessments must be equipped to address women's informational needs, relieve emotionality, and plan next steps after positive screens. Finally, to minimize differential screening uptake, health care systems must prioritize equity in program design and contribute to external educational and outreach efforts., Conclusion: Young women see pragmatic opportunities for health systems to optimize HBOC screening implementation., (Copyright © 2024 Jacobs Institute of Women's Health, George Washington University. Published by Elsevier Inc. All rights reserved.)

Recent studies propose fallopian tubes as the tissue origin for many ovarian epithelial cancers. To further support this paradigm, we assessed whether salpingectomy for treating ectopic pregnancy had a protective effect using the Taiwan Longitudinal National Health Research Database. We identified 316 882 women with surgical treatment for ectopic pregnancy and 3 168 820 age- and index-date-matched controls from 2000 to 2016. In a nested cohort, 91.5% of cases underwent unilateral salpingectomy, suggesting that most surgically managed patients have salpingectomy. Over a follow-up period of 17 years, the ovarian carcinoma incidence was 0.0069 (95% confidence interval [CI] = 0.0060 to 0.0079) and 0.0089 (95% CI = 0.0086 to 0.0092) in the ectopic pregnancy and the control groups, respectively (P < .001). After adjusting the events to per 100 person-years, the hazard ratio (HR) in the ectopic pregnancy group was 0.70 (95% CI = 0.61 to 0.80). The risk reduction occurred only in epithelial ovarian cancer (HR = 0.73, 95% CI = 0.63 to 0.86) and not in non-epithelial subtypes. These findings show a decrease in ovarian carcinoma incidence after salpingectomy for treating ectopic pregnancy., (© The Author(s) 2024. Published by Oxford University Press.)

Objectives: Opportunistic salpingectomy (OS) is the removal of fallopian tubes during another pelvic surgery for the purpose of ovarian cancer prevention. Herein, we describe the rates of OS at the time of hysterectomy and tubal sterilization between 2017 and 2020., Methods: This study uses the Canadian Institute of Health Information's Discharge Abstract Database and National Ambulatory Care Reporting System for all Canadian provinces and territories except for Quebec between the fiscal years 2017 and 2020. A descriptive analysis on all people aged 15 years and older who had hysterectomies or tubal sterilizations was conducted to determine the proportion of hysterectomies that included bilateral salpingectomy (OS) and the proportion of tubal sterilizations that were OS compared to tubal ligation., Results: There were 174 006 people included in the study. The proportion of hysterectomies that included OS increased from 31.7% in 2017 to 39.9% by 2020. With respect to tubal sterilizations, rates of OS increased from 26.3% of all tubal sterilizations in 2017 to 42.5% in 2020. British Columbia remained the jurisdiction with the highest rates of OS, but rates increased significantly in many jurisdictions, particularly at the time of tubal sterilization., Conclusion: The rates of OS have continued to increase in all Canadian jurisdictions following the official Society of Obstetricians and Gynaecologists of Canada recommendation to consider OS in 2015. Assuming that all tubal ligations could have been OS and 75% of hysterectomies with ovarian conservation could have included OS, our data indicate 76 932 missed opportunities for ovarian cancer prevention., (Copyright © 2023 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Ovarian cancer remains the most lethal gynaecological malignancy with 314 000 cases and 207 000 deaths annually worldwide. Ovarian cancer cases and deaths are predicted to increase in Australia by 42% and 55% respectively by 2040. Earlier detection and significant downstaging of ovarian cancer have been demonstrated with multimodal screening in the largest randomised controlled trial of ovarian cancer screening in women at average population risk. However, none of the randomised trials have demonstrated a mortality benefit. Therefore, ovarian cancer screening is not currently recommended in women at average population risk. More frequent surveillance for ovarian cancer every three to four months in women at high risk has shown good performance characteristics and significant downstaging, but there is no available information on a survival benefit. Population testing offers an emerging novel strategy to identify women at high risk who can benefit from ovarian cancer prevention. Novel multicancer early detection biomarker, longitudinal multiple marker strategies, and new biomarkers are being investigated and evaluated for ovarian cancer screening. Risk-reducing salpingo-oophorectomy (RRSO) decreases ovarian cancer incidence and mortality and is recommended for women at over a 4-5% lifetime risk of ovarian cancer. Pre-menopausal women without contraindications to hormone replacement therapy (HRT) undergoing RRSO should be offered HRT until 51 years of age to minimise the detrimental consequences of premature menopause. Currently risk-reducing early salpingectomy and delayed oophorectomy (RRESDO) should only be offered to women at increased risk of ovarian cancer within the context of a research trial. Pre-menopausal early salpingectomy is associated with fewer menopausal symptoms and better sexual function than bilateral salpingo-oophorectomy. A Sectioning and Extensively Examining the Fimbria (SEE-FIM) protocol should be used for histopathological assessment in women at high risk of ovarian cancer who are undergoing surgical prevention. Opportunistic salpingectomy may be offered at routine gynaecological surgery to all women who have completed their family. Long term prospective opportunistic salpingectomy studies are needed to determine the effect size of ovarian cancer risk reduction and the impact on menopause., (© 2024 The Authors. Medical Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of AMPCo Pty Ltd.)

Objective: To study and quantify the attitude of BRCA1/2 mutation carriers towards surgical risk reduction procedures., Methods: This cross-sectional national study was conducted by distribution of an anonymous questionnaire on social media platforms and to BRCA1/2 carriers' medical clinic., Results: 530 BRCA1/2 mutation carriers answered the survey. Risk reduction bilateral salpingo-oophorectomy was discussed with 447/489 (91%) of patients and performed in 260/489 (53%). Hormonal replacement therapy was discussed in 280/474 (59%) of patients. Addition of hysterectomy to risk reduction bilateral salpingo-oophorectomy was discussed in 129/481 (27%) of patients and performed in 44/443(10%). Age over 35 years at time of mutation detection was found to be significant in raising risk reduction bilateral salpingo-oophorectomy and hysterectomy performance rates. Risk reduction mastectomy was discussed in 390/471 (83%) of patients and performed in 156/471 (33%). In a multivariate analysis, BRCA1 mutation carriers (OR=1.66 (95% CI 1.07 to 2.57), p=0.024) and a personal cancer history leading to the mutation detection (OR=4.75 (95% CI 1.82 to 12.4), p=0.001) were found to be significant in increasing the likelihood of opting for risk reduction mastectomy. Additionally, highest risk reduction mastectomy performance rates were observed in the group of patients with a first-degree family history of breast cancer under the age of 50 years (OR=1.58 (95% CI 1.07 to 2.32), p=0.01)., Conclusions: This study highlights the high performance rates of risk reduction bilateral salpingo-oophorectomy, while hysterectomy was added in 10%, and that despite high awareness and acceptance rates for risk reduction mastectomy, only 33% had the procedure. The data presented provides insights for the clinician counseling BRCA1/2 mutation carriers, with regards to adherence to recommendations, understanding their concerns towards treatment and management alternatives; and finally, to construct a personalized management medical plan., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: Pathogenic variants (PVs) in BRCA1, BRCA2, PALB2, RAD51C, RAD51D, and BRIP1 cancer susceptibility genes (CSGs) confer an increased ovarian cancer (OC) risk, with BRCA1, BRCA2, PALB2, RAD51C, and RAD51D PVs also conferring an elevated breast cancer (BC) risk. Risk-reducing surgery, medical prevention, and BC surveillance offer the opportunity to prevent cancers and deaths, but their cost-effectiveness for individual CSGs remains poorly addressed., Objective: To estimate the cost-effectiveness of prevention strategies for OC and BC among individuals carrying PVs in the previously listed CSGs., Design, Setting, and Participants: In this economic evaluation, a decision-analytic Markov model evaluated the cost-effectiveness of risk-reducing salpingo-oophorectomy (RRSO) and, where relevant, risk-reducing mastectomy (RRM) compared with nonsurgical interventions (including BC surveillance and medical prevention for increased BC risk) from December 1, 2022, to August 31, 2023. The analysis took a UK payer perspective with a lifetime horizon. The simulated cohort consisted of women aged 30 years who carried BRCA1, BRCA2, PALB2, RAD51C, RAD51D, or BRIP1 PVs. Appropriate sensitivity and scenario analyses were performed., Exposures: CSG-specific interventions, including RRSO at age 35 to 50 years with or without BC surveillance and medical prevention (ie, tamoxifen or anastrozole) from age 30 or 40 years, RRM at age 30 to 40 years, both RRSO and RRM, BC surveillance and medical prevention, or no intervention., Main Outcomes and Measures: The incremental cost-effectiveness ratio (ICER) was calculated as incremental cost per quality-adjusted life-year (QALY) gained. OC and BC cases and deaths were estimated., Results: In the simulated cohort of women aged 30 years with no cancer, undergoing both RRSO and RRM was most cost-effective for individuals carrying BRCA1 (RRM at age 30 years; RRSO at age 35 years), BRCA2 (RRM at age 35 years; RRSO at age 40 years), and PALB2 (RRM at age 40 years; RRSO at age 45 years) PVs. The corresponding ICERs were -£1942/QALY (-$2680/QALY), -£89/QALY (-$123/QALY), and £2381/QALY ($3286/QALY), respectively. RRSO at age 45 years was cost-effective for RAD51C, RAD51D, and BRIP1 PV carriers compared with nonsurgical strategies. The corresponding ICERs were £962/QALY ($1328/QALY), £771/QALY ($1064/QALY), and £2355/QALY ($3250/QALY), respectively. The most cost-effective preventive strategy per 1000 PV carriers could prevent 923 OC and BC cases and 302 deaths among those carrying BRCA1; 686 OC and BC cases and 170 deaths for BRCA2; 464 OC and BC cases and 130 deaths for PALB2; 102 OC cases and 64 deaths for RAD51C; 118 OC cases and 76 deaths for RAD51D; and 55 OC cases and 37 deaths for BRIP1. Probabilistic sensitivity analysis indicated both RRSO and RRM were most cost-effective in 96.5%, 89.2%, and 84.8% of simulations for BRCA1, BRCA2, and PALB2 PVs, respectively, while RRSO was cost-effective in approximately 100% of simulations for RAD51C, RAD51D, and BRIP1 PVs., Conclusions and Relevance: In this cost-effectiveness study, RRSO with or without RRM at varying optimal ages was cost-effective compared with nonsurgical strategies for individuals who carried BRCA1, BRCA2, PALB2, RAD51C, RAD51D, or BRIP1 PVs. These findings support personalizing risk-reducing surgery and guideline recommendations for individual CSG-specific OC and BC risk management.

We developed a curriculum for community health workers (CHWs) using an innovative, community-engaged focus group and Delphi process approach. Equipping CHWs with knowledge of hereditary breast and ovarian cancer syndrome (HBOC) and genetics could help enhance identification of women at risk for HBOC, referral, and navigation through genetic services. We conducted focus groups with five CHWs and a three-round Delphi process with eight experts. In the first round of the Delphi process, participants rated and commented on draft curriculum modules. The second round involved live video discussion to highlight points of confusion and concern in the modules. The curriculum was revised and refined based on quantitative and qualitative data and reassessed by the experts in Round 3. Ultimately, agreement was achieved on eight of 10 modules when assessing for clarity of learning objectives, seven out of 10 when assessing for adult learning theory, and nine out of 10 when assessing for participants' ability to learn desired knowledge. We plan to virtually deliver this curriculum to CHWs to enhance their HBOC and genomic competencies. By equipping CHWs to understand and participate in genomics education, we can enable more equitable participation in genomics-informed clinical care and research. Beyond this curriculum, the Delphi methodology can further be used to design content for new CHW curriculums., (© 2023. The Author(s) under exclusive licence to American Association for Cancer Education.)

Objective: In this study, we aimed to develop education to assist BRCA mutation carriers in making informed decisions about HRT in the context of risk-reducing surgery, while simultaneously clarifying their treatment-specific values and reducing decisional conflict., Methods: We enrolled premenopausal BRCA mutation carriers ages 19-49 without prior cancer or risk-reducing salpingo-oophorectomy to structured interviews in which they reviewed education about the risks and benefits of HRT. Materials included literature-derived data demonstrating associations between HRT and commonly considered health outcomes (breast cancer, vasomotor symptoms, sexual functioning, cardiovascular disease, osteoporosis, and blood clots). Participants completed the 16-item Decisional Conflict Scale (DCS) before and after education, communicated their preferences by rating and ranking the six outcomes, and provided feedback to inform iterative revisions of the educational content., Results: 25 participants completed interviews. DCS scores decreased significantly from 54.6 to 22.8 following education (p < 0.001); sub-scores for uncertainty (71.7 to 37.3), informed (71.7 to 15.3), values clarity (53.7 to 17.0), effective decision (44.2 to 25.5), and support (35.0 to 17.7) also decreased significantly. Participants ranked cardiovascular disease as the most important outcome to consider, followed by breast cancer, osteoporosis, blood clots, decline in sexual function, and hot flashes. Participants with prior mastectomy (N = 10) ranked breast cancer as the most important outcome 25% of the time, compared to 80% in participants without mastectomy (N = 15)., Conclusion: Following education, BRCA mutation carriers had significantly less decisional conflict regarding the choice to use HRT. This pilot study was successful in generating a prototype educational aid for further testing., Competing Interests: Declaration of Competing Interest There are no conflicts of interest or financial disclosures for any of the manuscript authors. This work was supported by the Gray Foundation., (Copyright © 2023. Published by Elsevier Inc.)

Competing Interests: Competing interests: None declared.