This cohort study evaluates the reduction in risk of high-grade serous carcinoma among women undergoing opportunistic bilateral salpingectomy in Canada.

OBJECTIVE:To examine the association between post-diagnosis use of estrogen hormone therapy (EHT) and survival among patients diagnosed with invasive epithelial ovarian cancer by histotype before the age of 60. METHODS:In this retrospective, population-based, cohort study, we included all patients diagnosed with invasive epithelial ovarian cancer (EOC) between January 1, 1997, and December 31, 2020, who were under age 60 at diagnosis and survived at least one year after diagnosis. EHT use was restricted to systemic use, defined using provincial pharmacy dispensation records. We compared the survival of post-diagnosis EHT users to hormone therapy (HT) non-users using Cox proportional hazards regression with EHT use as a time-varying exposure and using a landmark analysis. RESULTS:Of the 2334 people included, 19.1% (n = 446) used EHT after their cancer diagnosis. EHT use was significantly associated with improved survival among people with serous ([adjusted hazard ratio [aHR], 0.71, 95% [CI] 0.58-0.87) and clear cell EOC (aHR, 0.52, 95% [CI] 0.28-0.97). As most of serous EOC is high-grade, this improved survival applies to high-grade serous cancer (HGSC). In contrast, EHT users showed worse survival among patients with the endometrioid histotype (aHR, 2.01, 95% [CI] 1.16-3.51). CONCLUSION:Post-diagnosis use of EHT is safe for patients diagnosed under age 60 with HGSC and likely for clear cell EOC. Thus, EHT can be used to manage menopausal sequelae in these patients. Our data suggest caution is warranted in patients with endometrioid EOC. More research is needed to understand the relationship between EHT and mucinous EOC survival.

RNA-binding proteins (RBPs) orchestrate post-transcriptional processes, including splicing, cleavage and polyadenylation, and translation. Our updated RBP resource integrates data from 92 additional RBPs (286 in total) profiled by enhanced CLIP (eCLIP), enabling comprehensive characterization of RNA elements within human K562 and HepG2 cells. To interrogate RBP-binding syntax, we trained deep-learning models on eCLIP profiles, allowing us to score genetic variants and quantify constraints on RBP-binding sites. We observed opposing selective-constraint profiles at splicing enhancers versus silencers, including an unexpected enrichment of strengthening mutations in ELAVL1- and HNRNPC-binding sites. Finally, our model prioritizes disease variants, exposing unexpected RBP-related mechanisms of pathogenesis, exemplified by the enrichment of weakening mutations in spliceosomal protein-binding sites among retinal disease variants. The complete eCLIP resource offers an integrated platform for exploring RBP-RNA interactomes.

QuestionDoes true self-acupressure, learned through a mobile app, improve cancer-related fatigue in women with ovarian cancer compared with sham self-acupressure and usual care?FindingsIn this randomized clinical trial of 171 women, the proportion achieving a clinically normal fatigue level at the end of treatment was 58% for true self-acupressure, 51% for sham self-acupressure, and 18% for usual care, representing a significant difference between true or sham self-acupressure vs usual care.MeaningThe findings suggest that self-acupressure, learned through a mobile app, offers a possible low-cost option for managing cancer-related fatigue in women diagnosed with ovarian cancer. This randomized clinical trial investigates whether true self-acupressure, learned through a mobile app, improves cancer-related fatigue in women surviving ovarian cancer compared with sham self-acupressure and usual care. ImportanceFatigue is a burdensome effect of ovarian cancer that is associated with poor sleep and quality of life. Self-acupressure is recommended in clinical guidelines but has substantial barriers to implementation. Use of a mobile app may address these barriers.ObjectiveTo investigate whether 6 weeks of true self-acupressure (TSA), learned via a mobile app, improves cancer fatigue, sleep, and quality of life in women with ovarian cancer compared with sham self-acupressure (SSA) and usual care (UC) and whether changes are sustained during an 18-week washout period.Design, Setting, and ParticipantsThis phase 3 single-blind randomized clinical trial was conducted from October 2019 to December 2023. Data collection ended in November 2024. Participants included ovarian cancer survivors who were fatigued (based on a Brief Fatigue Inventory [BFI] score >= 4) and who were recruited from tumor registries and social media.InterventionRandomization (1:1:1) to 6 weeks of TSA or SSA, taught via mobile app, or UC.Main Outcomes and MeasuresThe primary outcome was the change in the BFI from baseline to week 6. Secondary analyses were the BFI score at week 24 and sleep disturbance (based on the Pittsburgh Sleep Quality Index) and quality of life (based on the Functional Assessment of Cancer Therapy-Ovarian) administered at baseline and at weeks 6, 12, and 24.ResultsAmong the 360 participants who were screened, 171 women were randomized (mean [SD] age, 56 [12] years). Of the 160 participants who were allocated to the arms, 53 (33.1%) received TSA, 56 (35.0%) received SSA, and 51 (31.9%) received UC. Of these, the proportion achieving a clinically normal fatigue level at the end of treatment was 58.5% for the TSA arm, 51.1% for the SSA arm, and 17.6% for the UC arm. At 6 weeks, the BFI change scores were significantly better in the TSA arm but not in the SSA arm when they were compared with the UC-only arm (TSA vs UC: adjusted mean difference, -1.23 [95% CI, -2.17 to -0.29] and SSA vs UC: adjusted mean difference, -0.91 [95% CI, -1.83 to 0.02]). TSA and SSA change scores did not differ significantly from one another. The relative benefit of self-acupressure compared with UC on fatigue persisted at 24 weeks (TSA vs UC: mean difference, -1.38 [95% CI, -2.36 to -0.41] and SSA vs UC: mean difference, -0.97 [95% CI, -1.93 to -0.02]). Neither TSA nor SSA was significantly different than UC or each other for sleep quality. Only TSA significantly improved quality of life vs UC (odds ratio, 2.85 [95% CI, 1.20 to 6.80]). Neither true nor sham self-acupressure led to any adverse events.Conclusions and RelevanceIn this randomized clinical trial, TSA and SSA significantly reduced fatigue compared with UC, and these changes were both clinically meaningful and sustained. No impact was observed on sleep quality. Self-acupressure, taught via a mobile app, offered a safe and low-cost option for managing cancer fatigue.Trial registrationClinicalTrials.gov Identifier: NCT03763838

BACKGROUND:Prior studies have examined survival in patients with epithelial ovarian cancer (EOC); however, few consider race and ethnicity, particularly disaggregating Asian and Native Hawaiian/Pacific Islander women. METHODS:We analysed data from 18 Ovarian Cancer Association Consortium studies, including women with EOC from Asian (n = 697), non-Hispanic Black (n = 267), Hispanic (n = 492), Native Hawaiian/Pacific Islander (n = 98) and non-Hispanic White (n = 12,998) racial and ethnic groups. We ran Cox proportional hazards models estimating overall survival by race and ethnicity, adjusting for age, stage, year of diagnosis, and histotype, with fully adjusted models accounting for body mass index, smoking, and postmenopausal hormone use. We also examined associations between hormone-related factors and family history and overall survival by race and ethnicity, testing for heterogeneity. RESULTS:Compared to non-Hispanic White women with EOC, Native Hawaiian/Pacific Islander and non-Hispanic Black women had poorer overall survival (Hazard Ratios, HR = 1.58, 95% CI = 1.16-2.16, and HR = 1.31, 95% CI = 1.12-1.54, respectively). The association was more pronounced for Native Hawaiian/Pacific Islander women with high-grade serous carcinoma (HR = 2.00, 95% CI = 1.37-2.92). There was no significant heterogeneity in the associations between epidemiological factors and survival by racial and ethnic groups (p ≥ 0.31). DISCUSSION:Native Hawaiian/Pacific Islander and non-Hispanic Black women with EOC had poorer survival, highlighting the need to address disparities in outcome.

BACKGROUND:Opportunistic bilateral salpingectomy (OBS), the removal of fallopian tubes during hysterectomy or instead of tubal ligation, is recommended to reduce ovarian cancer risk. However, data on the effectiveness of prophylactic OBS is limited. METHODS:This population-based retrospective cohort included individuals aged 18-80 in Ontario, Canada, who underwent OBS or comparator surgeries (hysterectomy with ovarian and tubal conservation or tubal ligation) from 2011 to 2023. Individuals with gynecologic cancer before or within six months of surgery were excluded. Hazard ratios and 95% confidence intervals were estimated using Cox proportional hazards regression. Sensitivity analyses varied the time between surgery and cancer diagnosis to account for pre-existing serous tubal intraepithelial carcinomas. RESULTS:Among 196,839 individuals, 57,941 underwent OBS and 138,898 underwent comparator surgeries. 142 epithelial ovarian cancers were diagnosed (19 in the OBS group and 123 in the comparator surgery group). OBS was associated with reduced risk of any ovarian carcinoma, with an adjusted hazard ratio (aHR) of 0.60 (95% CI, 0.36 to 0.98). For serous ovarian carcinoma (high- and low-grade combined due to missing grade data), the aHR was 0.47 (95% CI, 0.22 to 0.99). Sensitivity analyses with 12- and 18-month intervals showed aHRs of 0.59 (95% CI, 0.35 to 0.99) and 0.60 (95% CI, 0.35 to 1.01) for all ovarian carcinomas, and 0.49 (95% CI, 0.23 to 1.01) and 0.47 (95% CI, 0.22 to 0.99) for serous ovarian carcinoma, respectively. CONCLUSIONS:OBS was associated with reduced risk of ovarian carcinoma, supporting its role as a primary prevention strategy.

OBJECTIVES:This study reports trends in reversible and permanent contraceptive use among females aged 15-44 in British Columbia (BC), Canada, from 2001 to 2021. STUDY DESIGN:Using a retrospective, population-based design, we analyzed data from BC Pharmanet, healthcare visits, and hospital records for females (as registered by the provincial insurance program), aged 15-44 in BC. Contraceptive options included short-acting reversible contraceptives (combined oral contraceptives [COC], progestin-only pills, vaginal rings, transdermal contraceptives), long-acting reversible contraceptives (levonorgestrel intrauterine devices [LNG-IUD], copper intrauterine devices), and permanent contraception (tubal ligation, bilateral salpingectomy). We measured IUD use in incident (number of insertions per year) and prevalent use (number of estimated users per year). RESULTS:From 2001 to 2021, the incident and prevalent use of the LNG-IUD in women aged 15-44 living in BC increased from 0.0% to 1.9%, and from 0.0% to 11.7%. The incidence of COC use decreased from 20.5% to 14.4%. Tubal ligation incidence declined from 0.4% to 0.0%, and bilateral salpingectomy incidence increased from 0.0% to 0.2%. Overall, these permanent contraception methods decreased from 0.4% to 0.3%. Younger age groups increasingly opted for LNG-IUDs, as illustrated by a median age decrease from 33.3 to 30.1 from 2001 to 2021. CONCLUSIONS:We observed pronounced shifts away from the use of COC towards the LNG-IUD, which was larger in younger age groups. Despite a pronounced move away from tubal ligation and toward bilateral salpingectomy for permanent contraception, there were fewer seeking permanent contraception. IMPLICATIONS:In British Columbia from 2001 to 2021, contraceptive use shifted away from short-acting reversible methods toward long-acting reversible methods, suggesting a change to more effective methods for reducing unintended pregnancies. While bilateral salpingectomy rates increased and tubal ligation rates decreased (reflecting the recommendations to perform bilateral salpingectomy for ovarian cancer risk reduction), female permanent contraception rates decreased overall.

Importance:Fatigue is a burdensome effect of ovarian cancer that is associated with poor sleep and quality of life. Self-acupressure is recommended in clinical guidelines but has substantial barriers to implementation. Use of a mobile app may address these barriers. Objective:To investigate whether 6 weeks of true self-acupressure (TSA), learned via a mobile app, improves cancer fatigue, sleep, and quality of life in women with ovarian cancer compared with sham self-acupressure (SSA) and usual care (UC) and whether changes are sustained during an 18-week washout period. Design, Setting, and Participants:This phase 3 single-blind randomized clinical trial was conducted from October 2019 to December 2023. Data collection ended in November 2024. Participants included ovarian cancer survivors who were fatigued (based on a Brief Fatigue Inventory [BFI] score ≥4) and who were recruited from tumor registries and social media. Intervention:Randomization (1:1:1) to 6 weeks of TSA or SSA, taught via mobile app, or UC. Main Outcomes and Measures:The primary outcome was the change in the BFI from baseline to week 6. Secondary analyses were the BFI score at week 24 and sleep disturbance (based on the Pittsburgh Sleep Quality Index) and quality of life (based on the Functional Assessment of Cancer Therapy-Ovarian) administered at baseline and at weeks 6, 12, and 24. Results:Among the 360 participants who were screened, 171 women were randomized (mean [SD] age, 56 [12] years). Of the 160 participants who were allocated to the arms, 53 (33.1%) received TSA, 56 (35.0%) received SSA, and 51 (31.9%) received UC. Of these, the proportion achieving a clinically normal fatigue level at the end of treatment was 58.5% for the TSA arm, 51.1% for the SSA arm, and 17.6% for the UC arm. At 6 weeks, the BFI change scores were significantly better in the TSA arm but not in the SSA arm when they were compared with the UC-only arm (TSA vs UC: adjusted mean difference, -1.23 [95% CI, -2.17 to -0.29] and SSA vs UC: adjusted mean difference, -0.91 [95% CI, -1.83 to 0.02]). TSA and SSA change scores did not differ significantly from one another. The relative benefit of self-acupressure compared with UC on fatigue persisted at 24 weeks (TSA vs UC: mean difference, -1.38 [95% CI, -2.36 to -0.41] and SSA vs UC: mean difference, -0.97 [95% CI, -1.93 to -0.02]). Neither TSA nor SSA was significantly different than UC or each other for sleep quality. Only TSA significantly improved quality of life vs UC (odds ratio, 2.85 [95% CI, 1.20 to 6.80]). Neither true nor sham self-acupressure led to any adverse events. Conclusions and Relevance:In this randomized clinical trial, TSA and SSA significantly reduced fatigue compared with UC, and these changes were both clinically meaningful and sustained. No impact was observed on sleep quality. Self-acupressure, taught via a mobile app, offered a safe and low-cost option for managing cancer fatigue. Trial registration:ClinicalTrials.gov Identifier: NCT03763838.

Electronic health records (EHRs) are valuable sources of data but are susceptible to biases from missing data and sample selection, often due to clinically informative visiting processes and non-probability sampling. This research explores whether genetic data, typically measured on nearly all participants in EHR-linked biobanks, can be used to mitigate these biases. Simulations were performed under conditions of missing completely at random (MCAR), missing at random (MAR), and missing not at random (MNAR) within random and biased sampling frameworks. We evaluated PRS-informed imputation, PRS-uninformed imputation, and complete case analysis across these scenarios in terms of bias, coverage, and root mean square error (RMSE) of the regression coefficient estimates. A real-world example using data from the Michigan Genomics Initiative (MGI, n = 68,063) compared the effectiveness of these methods against national benchmark estimates. PRS-informed imputation generally reduced bias and RMSE and improved coverage, particularly under MAR conditions in random samples. In analyses of biased samples of n = 10,000 with MAR exposure-only missingness, weighted, PRS-informed imputation analyses showed substantially lower percent bias (0.6%) and closer to nominal coverage (89.1%) compared to weighted, complete case analyses (9.4%; 74.3%). The MGI estimates showed that PRS-informed approaches aligned more closely with national benchmarks than unweighted complete case analysis. Leveraging genetic data with sample weighting can help reduce bias in outcome-exposure association estimates derived from biobank data. When available, researchers should consider including PRS for imputation and survey methods for sample weighting when estimating outcome-exposure association coefficients in a target population of interest, recognizing that benefits may vary by outcome and data structure.

Abstract BRCA-associated homologous recombination deficiency (HRD) is present in ~50% of high-grade serous carcinomas (HGSC) and predicts sensitivity to platinum-based therapy. However, there is little understanding of why some patients with BRCA-deficient tumors experience poor outcomes. In a large HGSC cohort (n = 1389) including 282 individuals with pathogenic germline BRCA variants (gBRCApv), residual disease after primary surgery has limited prognostic effect in gBRCApv-carriers compared to non-carriers, and prognostic outcomes differ based on the mutation location within functional domains of the BRCA genes. Multi-omic profiling is performed on 154 tumors, enriched for patients with BRCA-deficient tumors that experienced short overall survival ( ≤ 3 years, n = 42). Patients with BRCA2-deficient HGSC and loss of NF1 survive twice as long as those without NF1 loss, whereas PIK3CA, RAD21 and MYC amplification define BRCA2-deficient HGSC with exceptionally short survival. Patients with BRCA1-deficient HGSC and a more elevated HRD score survive significantly longer. BRCA1-deficient tumors in short survivors have evidence of immunosuppressive c-kit signaling and EMT. Our findings confirm that outcome is not determined by BRCA status alone, but rather a combination of co-occurring genomic alterations, the extent of DNA repair deficiency, and the tumor-immune microenvironment.

Survival and survivorship research in ovarian cancer has generated vital insights that can significantly impact the lives of people with the disease and their communities. However, there are persistent challenges in ensuring that research findings are effectively disseminated back to the individuals who contribute to and are most affected by this work. In the Multidisciplinary Ovarian Cancer Outcomes Group (MOCOG) study, engagement with patient advocates has highlighted an urgent need for accessible, understandable dissemination materials tailored to the needs of women living with and beyond ovarian cancer. Our advocates have emphasized a key principle: return of value. This concept involves ensuring that participants—whether research subjects or advocates—receive meaningful, actionable information in formats that are accessible to them. Responding to this need, MOCOG is co-designing a suite of lay materials summarizing our study findings, including visual abstracts and short-form audio and video content. This multipronged approach acknowledges diverse preferences and literacy levels within the survivor community, maximizing reach and impact. Input from advocates has driven our development process, from topic selection through to format and distribution channels. Recognizing advocates as integral partners, we have implemented mechanisms for their direct input, such as the creation of advocacy-driven question lists and interactive breakfast round tables with our expert research team. These efforts have catalyzed meaningful dialogue and mutual learning, reinforcing the importance of recognizing advocates as knowledge holders and ensuring the research process is responsive to their priorities. Also, advocates on MOCOG participated in research discussions and papers and were then in a position to advocate for follow-on studies that might help improve survival for women with ovarian cancer. Looking forward, study design processes are increasingly incorporating early-stage feedback from participants and advocates to ensure co-design and return of value are central considerations. This not only fosters trust and engagement but also increases the relevance and uptake of research findings within the survivor community. One example is the patient registry under development by Ovarian Cancer Research Alliance, which is built on the principles of early and continuous community engagement. Our experiences underscore the importance of designing research with return of value in mind, informed by authentic collaboration with those most impacted. As the field evolves, integrating community perspectives through partnerships and emerging platforms will be critical to maximizing the significance and reach of ovarian cancer research. Celeste Leigh Pearce, Gillian Hanley, Anne Chase, Cindy McKinnon. Deurloo, Jean Richardson, Bronwyn Grout. Full circle: Return of value to ovarian cancer research participants, advocates, and survivors [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Ovarian Cancer Research; 2025 Sep 19-21; Denver, CO. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl):Abstract nr IA002.

Severe COVID-19 among cancer (n = 12,995) and non-cancer patients (n = 34,693) who tested positive and had non-missing covariates. The results were from the model logit P(YSevereCOVID = 1|X, Cancer, Covariate) = β0 + βXX + βCancerCancer + βIntX × Cancer + βCovCovariate, where Covariate = Age + Race/Ethnicity + Sex + Disadvantage Index (quartile) + Comorbidity Score. Reference groups were age: 18 to 35, sex: female, BMI: 18.5 to 25, race: white/non-Hispanic, smoking status: never. A unit change in the continuous age variable is 10 years. The comorbidity score ranges from 0 to 6 and is the sum of indicators for presence of six categories of preexisting conditions in the electronic health record.

Abstract With evidence that salpingectomy is effective in preventing high-grade serous carcinoma, it is time to consider offering this procedure to people at higher-than-average lifetime risk for ovarian cancer, despite not having a pathogenic genetic variant that increases the risk for ovarian cancer. This targeted approach has potential to be effective at reducing ovarian cancer incidence, and unlike opportunistic salpingectomy, it is focused on people with an increased lifetime risk of ovarian cancer. However, the acceptability of this approach within the population of potential patients remains unknown. We conducted an online survey of adults in British Columbia, Canada, who were defined as “at risk” for ovarian cancer (i.e., people born with ovaries). Participants completed a questionnaire on demographics, ovarian cancer risk and protective factors, concerns about risk-reducing salpingectomy (RSS), and the risk they considered high enough to warrant RRS. We included 211 participants. Among these participants, 42% (n = 88) indicated that they would consider RRS at any lifetime risk or any risk above the population average. Another 20 participants chose risks between 1.5% and 4% for a cumulative 51% of the sample choosing risks below thresholds for oophorectomy. In contrast, 6% (n = 12) indicated that they would not consider the procedure at any risk level. None of the factors collected were associated with the likelihood that a person would find RRS acceptable. Overall, our participants showed broad interest in RRS as an ovarian cancer prevention strategy. These results suggest that there would likely be uptake if RRS was offered. Significance: This study found that many participants were willing to consider RRS to prevent ovarian cancer. Further research on RRS should be undertaken to understand how this can be best used for ovarian cancer prevention.

Supplementary Figures S1-S4

Schema of study numbers for each analysis to describe different cohort numbers due to pathology review and missing data. MOC, mucinous ovarian carcinoma; MBOT, mucinous borderline ovarian tumor; LGI, lower gastrointestinal; UGI, upper gastrointestinal; SISH, silver in situ hybridization.

Education pamphlet for participants

Codes used to define cancers diagnoses and treatments. Cancer sites are highlighted different colors and correspond to the highlighted rows of the same color in Table S1.

Logistic regression odds ratios (95% CI) for COVID-19 outcomes by chemotherapy treatment (without hematologic malignancy patients).

Sample characteristics of 211 participants

Phecodes corresponding to the comorbidity classes included in the comorbidity score and their counts in the analytic tested-positive cohort.