Search

ImportancePreventive bilateral salpingo-oophorectomy is offered to women at high risk of ovarian cancer who carry a pathogenic variant in BRCA1 or BRCA2; however, the association of oophorectomy with all-cause mortality has not been clearly defined.ObjectiveTo evaluate the association between bilateral oophorectomy and all-cause mortality among women with a BRCA1 or BRCA2 sequence variation.Design, setting, and participantsIn this international, longitudinal cohort study of women with BRCA sequence variations, information on bilateral oophorectomy was obtained via biennial questionnaire. Participants were women with a BRCA1 or BRCA2 sequence variation, no prior history of cancer, and at least 1 follow-up questionnaire completed. Women were followed up from age 35 to 75 years for incident cancers and deaths. Cox proportional hazards regression was used to estimate the hazard ratios (HRs) and 95% CIs for all-cause mortality associated with a bilateral oophorectomy (time dependent). Data analysis was performed from January 1 to June 1, 2023.ExposuresSelf-reported bilateral oophorectomy (with or without salpingectomy).Main outcomes and measuresAll-cause mortality, breast cancer-specific mortality, and ovarian cancer-specific mortality.ResultsThere were 4332 women (mean age, 42.6 years) enrolled in the cohort, of whom 2932 (67.8%) chose to undergo a preventive oophorectomy at a mean (range) age of 45.4 (23.0-77.0) years. After a mean follow-up of 9.0 years, 851 women had developed cancer and 228 had died; 57 died of ovarian or fallopian tube cancer, 58 died of breast cancer, 16 died of peritoneal cancer, and 97 died of other causes. The age-adjusted HR for all-cause mortality associated with oophorectomy was 0.32 (95% CI, 0.24-0.42; P

Background BRCA1 and BRCA2 (BRCA) mutation carriers face a high lifetime risk of developing ovarian cancer. Oral contraceptives are protective in this population; however, the impact of other types of contraception (e.g. intrauterine devices, implants, injections) is unknown. We undertook a matched case-control study to evaluate the relationship between type of contraception and risk of ovarian cancer among women with BRCA mutations. Methods A total of 1733 matched pairs were included in this analysis. Women were matched according to year of birth, date of study entry, country of residence, BRCA mutation type and history of breast cancer. Detailed information on hormonal, reproductive and lifestyle exposures were collected from a routinely administered questionnaire. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) associated with each contraceptive exposure. Results Ever use of any contraceptive was significantly associated with reduced risk of ovarian cancer (OR = 0.62; 95% CI 0.52-0.75; P

ObjectiveBRCA mutation carriers face a high lifetime risk of developing ovarian cancer. The strong inverse association between breastfeeding and the risk of ovarian cancer is established in the general population but is less well studied among women with a germline BRCA1 or BRCA2 mutation.MethodThus, we conducted a matched case-control analysis to evaluate the association between breastfeeding history and the risk of developing ovarian cancer. After matching for year of birth, country of residence, BRCA gene and personal history of breast cancer, a total of 1650 cases and 2702 controls were included in the analysis. Conditional logistic regression was used to estimate the odds ratio (OR) and 95% confidence intervals (CI) associated with various breastfeeding exposures.ResultsA history of ever-breastfeeding was associated with a 23% reduction in risk (OR = 0.77; 95%CI 0.66-0.90; P = 0.001). The protective effect increased with breastfeeding from one month to seven months after which the association was relatively stable. Compared to women who never breastfed, breastfeeding for seven or more months was associated with a 32% reduction in risk (OR = 0.68; 95%CI 0.57-0.81; P

Up to 20% of high-grade serous ovarian carcinomas (HGSOC) are hereditary; however, historical uptake of genetic testing is low. We used a unique combination of approaches to identify women in Ontario, Canada, with a first-degree relative (FDR) who died from HGSOC without prior genetic testing, and offer them multi-gene panel testing. From May 2015-Sept 2019, genetic counseling and testing was provided to eligible participants. Two recruitment strategies were employed, including self-identification in response to an outreach campaign and direct targeting of FDRs of deceased HGSOC patients treated at our institution. The rate of pathogenic variants (PV) in established/potential ovarian cancer risk genes and the benefits/challenges of each approach were assessed. A total of 564 women enrolled in response to our outreach campaign (n = 473) or direct recruitment (n = 91). Mean age at consent was 52 years and 96% did not meet provincial testing criteria. Genetic results were provided to 528 individuals from 458 families. The rate of PVs in ovarian cancer risk genes was highest when FDRs were diagnosed with HGSOC <60 years (9.4% vs. 3.9% ≥ 60y, p = 0.0160). Participants in the outreach vs. direct recruitment cohort had a similar rate of PVs; however, uptake of genetic testing (97% vs. 89%; p = 0.0036) and study completion (95% vs. 87%; p = 0.0062) rates were higher in the former. Eleven participants with pathogenic variants have completed risk-reducing gynecologic surgery, with one stage I HGSOC and two breast cancers identified. Overall PV rates in this large cohort were lower than expected; however, we provide evidence that genetic testing criteria in Ontario should include individuals with a deceased FDR diagnosed with HGSOC <60 years of age. • Due to limits in Ontario's genetic testing criteria, we tested first-degree relatives of deceased ovarian cancer patients. • Pathogenic variants were found in 10% of participants; rates were highest when a relative was diagnosed prior to age 60. • All participants discussed results with their relatives and engaged in enhanced screening or risk reduction. • Our findings support changing genetic testing guidelines in Ontario and provide a framework to notify eligible individuals. [ABSTRACT FROM AUTHOR]

This study compares knowledge, experience and understanding of genetic testing, and psychological outcomes among breast and ovarian cancer patients undergoing multi-gene panel testing via genetic counselor-mediated (GMT) or oncologist-mediated (OMT) testing models. A pragmatic, prospective survey of breast and ovarian cancer patients pursuing genetic testing between January 2017 and August 2019 was conducted at the Princess Margaret Cancer Centre in Toronto, Canada. A total of 120 (80 GMT; 40 OMT) individuals completed a survey administered one week following consent to genetic testing. Compared to OMT, the GMT cohort had higher median knowledge (8 vs. 9; p = 0.025) and experience/understanding scores (8.5 vs. 10; p < 0.001) at the time of genetic testing. Significant differences were noted in the potential psychological concerns experienced, with individuals in the GMT cohort more likely to screen positive in the hereditary predisposition domain of the Psychosocial Aspects of Hereditary Cancer tool (55% vs. 27.5%; p = 0.005), and individuals in the OMT cohort more likely to screen positive in the general emotions domain (65.0% vs. 38.8%; p = 0.007). The results of this study suggest that OMT can be implemented to streamline genetic testing; however, post-test genetic counseling should remain available to all individuals undergoing genetic testing, to ensure any psychologic concerns are addressed and that individuals have a clear understanding of relevant implications and limitations of their test results. [ABSTRACT FROM AUTHOR]

This study compares the rate and time to genetic referral, and patient uptake of germline genetic services, before and after implementation of reflex BRCA1/2 tumor testing for high-grade serous ovarian cancer (HGSOC) in a universal healthcare system. A retrospective chart review of HSGOC patients diagnosed in the year before (PRE) and after (POST) implementation of reflex BRCA1/2 tumor testing was conducted. Clinical information (date/age at diagnosis, personal/family history of breast/ovarian cancer, cancer stage, primary treatment, tumor results) and dates of genetics referral, counseling, and germline testing were obtained. Incident rate ratios (IRR) and 95% CI were calculated using negative binomial regression. Time to referral was evaluated using Kaplan-Meier survival analysis. Fisher Exact tests were used to evaluate uptake of genetic services. 175 HGSOC patients were identified (81 PRE; 94 POST). Post-implementation of tumor testing, there was a higher rate of genetics referral (12.88 versus 7.10/1000 person-days; IRR = 1.60, 95% CI: 1.07–2.42) and a shorter median time from diagnosis to referral (59 days PRE, 33 days POST; p =.04). In the POST cohort, most patients were referred prior to receiving their tumor results (n = 63/77; 81.8%). Once referred, most patients attended genetic counseling (94.5% PRE, 97.6% POST; p =.418) and pursue germline testing (98.6% PRE; 100% POST; p =.455). Following implementation of reflex BRCA1/2 tumor testing for HGSOC, significant improvements to the rate and time to genetics referral were identified. Additional studies are needed to evaluate physician referral practices and the long-term impact of reflex tumor testing. • Improvements in the rate and time to genetics referral were seen after implementation of reflex BRCA1/2 tumor testing. • Clinicians referred HGSOC patients for germline testing irrespective of BRCA1/2 tumor results. • Reflex BRCA1/2 tumor test results were not available for all HGSOC patients, likely due to insufficient tumor tissue. • There is a high uptake of genetic counseling and germline testing among HGSOC patients, irrespective of tumor testing. • Reflex BRCA1/2 tumor testing can be implemented without compromising hereditary cancer risk assessment. [ABSTRACT FROM AUTHOR]

Abstract Objective Genetic testing identifies cancer patients who may benefit from targeted treatment and allows for enhanced cancer screening and risk-reduction in their at-risk relatives. Traditional models of genetic counseling (GC) cannot meet the increasing demand and urgency for genetic testing. The objective of this study was to evaluate a new model of service delivery to improve the efficiency of pre-test GC for panel-based genetic testing. Methods A parallel, two-armed, randomized non-inferiority study compared traditional and modified pre-test GC models (1:2) prior to panel-based genetic testing. Participants were adult females, whose first-degree relative died of serous ovarian cancer. In the modified group, participants were emailed a 20-minute presentation prior to a scheduled pre-test GC telephone call. Psychosocial and knowledge questionnaires were provided at baseline (P1) and one week after pre-test GC (P2). Results 382 women completed pre-test GC (256 modified, 126 traditional). There were no differences in marital status, education level or household income. Pre-test GC time was shorter in the modified group (average 19 vs. 46 min, p < 0.001), with no difference in post-test GC time (average 16 min each, p = 0.78). The modified pre-test GC model was found to be non-inferior to traditional GC on measures of cancer-specific distress, depression, anxiety, decisional conflict, ovarian cancer knowledge and satisfaction. Perceived lifetime risk for ovarian cancer decreased to a lesser extent from baseline in women who received modified pre-test GC. Conclusions A 20-minute presentation prior to pre-test telephone GC is non-inferior to traditional in-person GC on all variables tested, except for perceived ovarian cancer risk. This modified model improved GC efficiency without negatively affecting psychosocial outcomes, providing an alternative strategy to meet the growing demand for genetic testing. Highlights • We evaluated a modified pre-test genetic counseling (GC) model for women undergoing panel-based genetic testing. • Time spent with a genetic counselor was shorter in the modified pre-test GC compared to traditional pre-test GC. • Modified pre-test GC was non-inferior to traditional GC on psychosocial outcomes, ovarian cancer knowledge and satisfaction. • Our modified pre-test GC model provides an efficient and efficacious alternative for individuals undergoing panel testing. • Further research in a more diverse population and individuals being referred for clinical pre-test GC is needed. [ABSTRACT FROM AUTHOR]