Risk-reducing Salpingo-oophorectomy Research Articles

High-grade serous carcinoma occurring after risk-reducing salpingo-oophorectomy in BRCA1/2 germline pathogenic variant carriers.

Risk-reducing salpingo-oophorectomy (RRSO) effectively prevents high-grade serous carcinoma (HGSC) in BRCA1/2 germline pathogenic variant (GPV) carriers. Still, some women develop HGSC after RRSO without pathologic findings. This study assessed long-term incidence and risk factors for developing HGSC after RRSO without pathologic findings. BRCA1/2 GPV carriers were selected from Hereditary Breast and Ovarian cancer in the Netherlands (HEBON) cohort. Follow-up data for HGSC after RRSO were obtained from the Dutch Nationwide Pathology Databank (PALGA) and confirmed by histopathological review. Cumulative incidence rates of HGSC were calculated using Kaplan-Meier analyses. Cox proportional hazards model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for factors associated with an increased risk of HGSC following RRSO without pathologic findings. A total of 2519 women were included, with a median follow-up of 13.4 years (range: 0.0-27.6). The 20-years cumulative incidence rate of HGSC was 1.5% (95% CI: 0.0-2.1) for BRCA1 and 0.2% (95% CI: 0.0-1.4) for BRCA2 GPV carriers. All women who developed HGSC underwent RRSO after the recommended age. Incomplete embedding of the RRSO specimen (HR: 4.2, 95% CI: 1.4-12.6), higher age at RRSO (HR per year: 1.1, 95% CI: 1.0-1.1), and carrying a BRCA1 GPV (HR: 12.1, 95% CI: 1.6-91.2) were associated with increased risk of HGSC. In BRCA1/2 GPV carriers, long-term incidence of HGSC after RRSO without pathologic findings was low. Strict adherence to guidelines regarding timely RRSO followed by complete specimen embedding can further reduce the risk of HGSC in the years following RRSO.

Prevalence of cardiometabolic outcomes in women who underwent salpingo-oophorectomy to prevent hereditary breast and ovarian cancer: a meta-analysis.

Risk reduction salpingo-oophorectomy (RRSO) is usually performed in women with hereditary breast and ovarian cancer (HBOC) syndrome for BRCA1 and BRCA2 gene mutation carriers, resulting in surgical menopause, which is more associated with a high risk of cardiovascular and metabolic disease than in premenopausal and natural menopausal women. This study assessed the prevalence of cardiovascular and metabolic outcomes in women who underwent salpingo-oophorectomy as a preventive measure against HBOC. This meta-analysis assessed prevalence rates for four metabolic/cardiovascular conditions: myocardial infarction, hypertension, hypercholesterolemia, and type 2 diabetes mellitus. DerSimonian and Laird random-effects models were applied to all analyses, with 95% confidence interval (CI). Heterogeneity was assessed with I². We used OpenMeta Analyst software for statistical analysis. A total of five retrospective studies and one observational study involving 1,320 patients were included. The average body mass index (BMI) was 25.97kg/m2 and the average waist circumference was 87.94cm. The analysis across a mean 4.94-year follow-up revealed prevalence rates for acute myocardial infarction of 1.5% (95% CI 0.3-2.7; P = 0.077; I²=56.25%), hypertension of 28% (95% CI 6.9-49.1; P < 0.001; I2 = 98.42%), hypercholesterolemia of 27.2% (95% CI 6.8-47.6; P < 0.001; I²=98.67%), and type 2 diabetes mellitus of 3.3% (95% CI 1.1-5.5; P < 0.001; I²=82.44%). Our findings suggest that there is no marked increase in cardiovascular risk among women with HBOC undergoing RRSO.

Sexual function and menopausal symptoms among patients at high risk of ovarian carcinoma undergoing interval salpingectomy or risk-reducing salpingo-oophorectomy in the prospective multicenter WISP trial

Sexual function and menopausal symptoms among patients at high risk of ovarian carcinoma undergoing interval salpingectomy or risk-reducing salpingo-oophorectomy in the prospective multicenter WISP trial

Pattern Anlysis of Risk-Reducing Strategies in Unaffected Korean BRCA1/2 Mutation Carriers.

The lifetime risk of breast and ovarian cancer increases substantially for individuals with mutations in BRCA1/2. The evidence indicates that BRCA1/2 mutation carriers benefit from early cancer detection and prevention strategies. However, data on the patterns of risk-reducing interventions are lacking. This study investigated the patterns of surveillance and risk-reducing interventions among unaffected BRCA1/2 mutation carriers. A cohort of unaffected BRCA1/2 mutation carriers was identified from the Korean Hereditary Breast cAncer (KOHBRA) study database, and a telephone survey was conducted. The survey included questions on the incidence of new cancers, patterns of cancer (breast, ovarian, prostate, other) surveillance, chemoprevention, risk-reducing surgery, and reasons for participating in risk-reducing strategies. Between November 2016 and November 2020, 192 BRCA1/2 mutation carriers were contacted, of which 83 responded. After excluding 37 responders who refused to participate, 46 participants (15 males, 31 females) were included in the analysis. The mean ± SD follow-up time was 103 ± 17 months (median 107, range 68~154), and the mean ± SD age was 31 ± 8 years. Ten BRCA1/2 mutation carriers developed breast cancer, one developed ovarian cancer, and three developed other cancers. Six BRCA1/2 mutation carriers (19.4%) underwent annual breast cancer surveillance as recommended by guidelines, while none underwent ovarian or prostate cancer surveillance. Three carriers (9.7%) used chemoprevention for breast cancer. Risk-reducing salpingo-oophorectomy was performed on only one BRCA1/2 mutation carrier. The rates of breast/ovarian cancer surveillance, chemoprevention, and risk-reducing surgery were low among unaffected Korean BRCA1/2 mutation carriers. Given this cohort's relatively high risk of developing breast cancer, strategies to encourage active participation in risk reduction are needed.

Germline Genetic Susceptibility Testing Among Emirati Nationals at Risk for Hereditary Breast and Ovarian Cancer Syndrome.

Breast cancer among Emirati patients is characterized by early-onset disease and later stages at presentation. Little is known about the germline genetic variants that may contribute to these observations. The goal of this study is to characterize the rate and implications of germline genetic variants among a cohort of Emirati patients at risk for hereditary breast and ovarian cancer syndrome. A retrospective study was performed to analyze the results of clinical germline genetic testing (March 2020-January 2023) among a cohort of consecutive Emirati patients at risk for hereditary breast and ovarian cancer syndrome: group A: patients with personal history of breast or ovarian cancer (n = 135); group B: unaffected patients with family history of breast or ovarian cancer (n = 37); and group C: patients presenting for cascade testing (n = 20). Management of patients identified to have pathogenic/likely pathogenic (P/LP) variants was analyzed. The rate of P/LP germline variants for each group was: group A: 17.3%, group B: 16.6%, group C: 57.9%. BRCA1 gene was the most commonly identified gene harboring P/LP variants, followed by BRCA2, among this cohort. Four unrelated patients had a recurrent BRCA1 pathogenic variant: c.4065_4068del (p.Asn1355Lysfs*10). Only two patients in this series elected risk-reducing mastectomy and four patients elected risk-reducing bilateral salpingo-oophorectomy. A higher rate of P/LP variants is seen among Emirati patients at risk for hereditary breast and ovarian cancer syndrome compared with reports of similar patients from Western populations. Efforts to increase utilization and awareness of germline genetic testing are warranted among Emirati patients.

Impact of graphical display on the intention to undergo risk-reducing salpingo-oophorectomy and mastectomy in individuals positive for BRCA pathogenic variant

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.

Decision-making process for risk-reducing salpingo-oophorectomy among Korean women with hereditary breast cancer: A grounded theory study

PurposeTo explore the decision-making process regarding Risk-Reducing Salpingo-Oophorectomy (RRSO) among women with hereditary breast cancer in Korea, with a focus on complex interpersonal interactions and sociocultural influences. MethodThis qualitative, grounded theory study conducted semi-structured and in-depth interviews with 17 women with hereditary breast cancer between March and December 2021. Theoretical sampling and constant comparison were utilized for data analysis. ResultsThe core concept identified was ‘Navigating optimal trajectories for preserving myself,’ encompassing four stages: (1) conflicting between cancer-free health and maintaining integrated self; (2) recognizing the decision-maker: myself vs. physician; (3) seeking meaningful information; and (4) evaluating decision results and prioritizing values. Women’s conflict was influenced by the time given to decide, the timing of BRCA results, complexity of surgical choices, diverse perspectives, and the quality of information. This process often reiterated until RRSO was undertaken. ConclusionWomen with hereditary breast cancer grapple with conflicting decisions to preserve their integrated selves. The decision-making process is complex and subjective, influenced by physician-dominated decision-making culture, subjective meaningful information, individual values, and decisional circumstances. Supporting women in prioritizing their values and providing comprehensive information on the physical, emotional, relational, and social impacts of each option are crucial. Oncology nurses can play a vital role in bridging the gap between physician-dominated decision-making and patient autonomy by facilitating communication and supporting patient-centered care.

Sexual function following risk-reducing salpingo-oophorectomy: a prospective cohort study.

Increased access to and indications for genetic testing will lead to more women undergoing risk-reducing salpingo-oophorectomy (RRSO), with a potential impact on sexual function. Our objective was to prospectively investigate (1) sexual function in women with pathogenic variant (PV) in BRCA1/2 genes, before and 1 year after RRSO, and to compare with a healthy age-matched control group and (2) to study if testosterone levels correlate with sexual functioning after RRSO. A prospective observational follow-up study of 43 BRCA1/2-PV carriers planned for RRSO and 73 healthy-age matched controls. Data including personal medical history, the Female Sexual Function Index (FSFI) and blood samples for analysis of testosterone by tandem mass spectrometry and free androgen index (FAI) were collected before and 1 year after surgery or at inclusion (controls). Sexual function and testosterone levels following RRSO. Median age in the RRSO group was 42years at baseline, 55.8% were premenopausal and 53.5% had a history of breast cancer. The RRSO group had significantly lower median FSFI total score (P < .001), lower scores of all 6 FSFI domains (P < .001), as well as a higher proportion of female sexual dysfunction (FSD) (P < .001) compared to the control group at 1 year after surgery. In the RRSO group, users of menopausal hormone therapy (MHT) had a significantly higher median FSFI total score compared with the nonusers both at baseline (P = .023) and follow-up (P = .010). The proportion of FSD was significantly higher in the non-MHT group at both baseline (P = .041) and follow-up (P = .009). FAI was significantly lower in the RRSO group when compared to the controls at 1-year follow-up (P = .041); however, no significant correlations between testosterone levels and FSFI scores were found. The results highlight the need to counsel BRCA1/2-PV carriers before RRSO and offer a structured follow-up and support addressing sexual function and impact of MHT use. The main strength of this study is its prospective design with age-matched controls. Limitation is a small sample size. Our findings show that sexual function deteriorated 1 year after RRSO independent of testosterone levels, and the proportion with impaired sexual function was higher compared to healthy age-matched controls.

Uptake of Risk-Reducing Surgeries in an International Real-World Cohort of Hispanic Women.

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. 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. 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. 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.

Economic Evaluation of Population-Based BRCA1 and BRCA2 Testing in Canada

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. To estimate the incremental lifetime health outcomes, costs, and cost-effectiveness associated with population-based BRCA testing compared with FH-based testing in Canada. 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. 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. 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. 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.

Effects of Hormonal Replacement Therapy and Mindfulness-Based Stress Reduction on Climacteric Symptoms Following Risk-Reducing Salpingo-Oophorectomy.

Breast Cancer Associated Susceptibility Proteins Type 1/2 (BRCA1/2) promote cellular functioning by modulating NRF2-mediated antioxidant signaling. Redox failure in women with BRCA1/2 insufficiency increases the risk for breast/ovarian/uterine cancers. Risk-reducing salpingo-oophorectomy (RRSO) is a prophylactic surgery of the reproductive organs, which is frequently conducted by the age of 40 to lower the occurrence of cancer in women with BRCA1/2 mutations. However, abrupt estrogen decline following RRSO causes ovarian failure, which implicates various cellular physiological processes, resulting in the increased release of free radicals and subsequent severe onset of menopausal symptoms. Comfort measures (e.g., hormonal replacement therapy (HRT) and mindfulness-based stress reduction (MBSR)) may improve chronological menopause-related quality of life, but their specific effects are not clear in women with gene mutations. Aiming to fill the gap, this study used path analysis to examine the effects of HRT and MBSR on menopausal symptoms among RRSO patients (N = 199, mean age = 50.5 ± 6.7 years). HRT directly alleviated the levels of urogenital symptoms (β = -0.195, p = 0.005), which mediated its indirect significant effects on the somatic-vegetative and psychological symptoms of menopause (β = -0.046, -0.067; both p values = 0.004, respectively), especially in BRCA2 carriers and in women who were currently physically active, premenopausal at the time of RRSO, had a high BMI, and had no history of breast cancer. It increased the severity of urogenital symptoms in women with a history of cancer. MBSR, on the other hand, was associated with indirect increases in the intensity of the somatic-vegetative and psychological symptoms of menopause (β = 0.108, 0.029; p = 0.003, 0.033, respectively). It exerted positive direct effects on different menopausal symptoms in multigroup analysis. The results suggest that young women undergoing recent RRSO may benefit from HRT at an individual level, while their need for extensive measures to optimize their psychological wellbeing is ongoing. The adverse effects of MBSR, which are captured in the present study, imply that MBSR may interfere with redox sensitivity associated with estradiol fluctuations in BRCA1/2 carriers. Investigations are needed to test this hypothesis and elaborate on the underlying mechanisms in these women.

Basic knowledge for counseling patients undergoing risk-reducing salpingo-oophorectomy.

Significant progress has been made in the molecular diagnosis of cancer. It provides personalized medicine, including cancer diagnosis, prognosis, targeted therapy, and risk detection. These advances allow physicians to identify patients at risk for cancer before it develops and offer them an opportunity to prevent its development. Mutations in breast cancer susceptibility genes 1 and 2 (BRCA1 and 2) are one of the most well-known cancer-related gene mutations since actor Angelina Jolie shared her experience with genetic mutations and risk-reducing surgery in the media. In Korea, tests for germline BRCA1/2 mutations have been covered by insurance since May 2012 and the number of women of BRCA1/2 mutations has continued to increase over the past decade. Most carriers of BRCA1/2 mutations consider risk-reducing salpingo-oophorectomy (RRSO) resulting in early menopause and want to know the lifetime risks and benefits of RRSO. However, despite the increasing number of carriers of BRCA1/2 mutations, the counseling and management of patients requiring RRSO varies among physicians. This article provides basic knowledge on RRSO to help physicians comprehensively assess its risks and benefits and manage at-risk women.

Occult residual ovarian tissue at the time of minimally invasive risk reducing surgery in women with BRCA mutations

ObjectiveTo 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. MethodsA 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. ResultsTwenty 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. ConclusionIn 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.

The pathologic and clinical outcomes of risk-reducing salpingo-oophorectomy in asymptomatic carriers of homologous recombination repair gene mutation.

To investigate the prevalence of pathological findings and clinical outcomes of risk-reducing salpingo-oophorectomy (RRSO) in asymptomatic carriers with germline homologous recombination repair (HRR) gene pathogenic/likely pathogenic variants (PV/LPV). This retrospective study enrolled asymptomatic carriers with germline HR gene PV/LPV who underwent RRSO between 2006 and 2022 at the National Cancer Center in Korea. Clinical characteristics, including history of breast cancer, family history of ovarian/breast cancer, parity, and oral contraceptive use, were analyzed. Of the 255 women who underwent RRSO, 129 (50.6%) had PV/LPV in BRCA1, 121 (47.5%) in BRCA2, and 2 (0.7%) had both BRCA1 and BRCA2 PV/LPV. In addition, 1 carried PV/LPV in RAD51D, and 2 in BRIP1. Among the BRCA1/2 PV/LPV carriers, occult neoplasms were identified in 3.5% of patients: serous tubal intraepithelial carcinoma (1.1%, n=3), fallopian tubal cancers (0.8%, n=2), ovarian cancer (1.2%, n=3), and breast cancer (0.4%, n=1). Of the 9 patients with occult neoplasms, 5 (2.0%) were identified from the 178 breast cancer patients, and 4 (1.6%) were detected in 65 healthy mutation carriers. During the median follow-up period of 36.7 months (interquartile range, 25.9-71.4), 1 (0.4%) BRCA1 PV carrier with no precursor lesions at RRSO developed primary peritoneal carcinomatosis after 30.1 months. Women with HRR gene mutations PV/LPV who undergo RRSO are at a risk of detecting occult neoplasms, with a of 3.5%. Even in the absence of precursor lesions during RRSO, there was a cumulative risk of peritoneal carcinomatosis development, emphasizing the need for continued surveillance.

(112) SEXUAL HEALTH AFTER RISK REDUCING SALPINGO-OOPHERECTOMY FOR BRCA PATIENTS

Abstract Introduction There is no study assessing the changes in sexual health after risk reducing oopherectomy in premenopausal women. Objective Objective: To evaluate the effect of risk-reducing salpingo-oophorectomy (RRSO) on change in sexual function in women aged 34-50 years with pathogenic variants in BRCA1 or BRCA2 (BRCA1/2). Methods Methods: The PROSper (Prospective Research of Outcomes after Salpingo-oophorectomy) study is a prospective cohort of women aged 34-50 years with BRCA1 or two germline pathogenic variants that compares health outcomes after RRSO to a non-RRSO control group with ovarian conservation. Women aged 34-50 years, who were planning either RRSO or ovarian conservation, were enrolled for 3 years of follow-up. Sexual Function was measured using the Sexual Health Outcomes in Women (SHOW-Q) a validated survey tool that measures sexual desire, frequency, satisfaction, orgasm, and discomfort specifically in patients with a history of a pelvic condition, including oophorectomy. Differences in sexual function between the RRSO and non-RRSO groups, were determined by using mixed effects multivariable linear regression models. Results Results: Of 100 PROSper participants, all completed SHOW Q. At baseline patients who had undergone RRSO before enrollment had lower SHOW-Q scores (71 vs 64). Across all 60 months of the study the SHOW-Q scores remained persistently lower in those undergoing RRSO raging from 6-13 points across the time studied (p &amp;lt;0.05) controlling for age, depression, partner, menopausal symptoms and hormone therapy Conclusions Conclusion: Women with pathogenic variants in BRCA1/2 who undergo RRSO before the age of 50 years have greater effects on sexual function than those that do not. The detrimental effect of rRRSO is not otherwise explained by hormone therapy, depression or menopausal symptoms. This information should be incorporated into counseling and post op management to consider options to improve sexual health post surgery Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: sprout pharma.

Risk-reducing salpingo-oophorectomy among diverse patients with BRCA mutations at an urban public hospital: a mixed methods study

ObjectivesTo 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.DesignRetrospective cohort, semistructured qualitative interviews.Setting and...

Uptake of risk-reduction, surveillance, and therapeutic interventions among patients with breast cancer with pathogenic germline variants.

10579 Background: Management of breast cancer (BC) patients with pathogenic germline variants (PGVs) can include risk-reducing bilateral mastectomy (BLM), PARP inhibitors (PARPi), enhanced breast imaging (MRI/tomosynthesis), risk-reducing salpingo-oophorectomy (RRSO) and pancreatic cancer surveillance (endoscopic ultrasound, EUS/MR cholangiopancreatography, MRCP). We assessed intervention uptake in &gt;1,400 PGV-positive BC patients. Methods: Germline genetic testing (GGT) data (Invitae Corp.) and insurance claims data (Komodo Healthcare Map) were assembled for female patients with BC or DCIS diagnosed 2015-23, GGT &lt;120 days from diagnosis, and &gt;1 year of claims post-GGT. Inclusion/exclusion criteria followed prior work (PMID 32027353). Genes analyzed were those conferring high (&gt;50%; BRCA1, BRCA2, CDH1, PALB2, PTEN, STK11, TP53) or moderate (20-50%; ATM, BARD1, CHEK2, NF1, RAD51C, RAD51D) BC risk. Multivariable logistic regression models of intervention use included PGV risk, race/ethnicity, age, family cancer history, local metastasis, type of insurance, geographic region and time from diagnosis to GGT. Chi-square tests were used to compare intervention uptake rates by PGV risk (Table). Results: 1,432 patients had &gt;1 PGV in a high- (51%) or moderate-risk (49%) gene: 68% White, 32% lymph node involvement, 69% BC family history, 28% Medicare/Medicaid, mean (SD) age at testing: 51 (12) and mean (SD) days from diagnosis to GGT: 40 (26). The intervention with the highest uptake was BLM (60% in all PGV carriers). BLM, RRSO, and PARPi were significantly more frequent in high- vs. moderate-risk PGV carriers. In the multivariable model, patients with BLM uptake were younger (odds ratio, OR 0.9, 95% confidence interval, CI 0.9-1), more often had family cancer history reported (OR 2, 95% CI 1-3) and had high-risk PGV (OR 5, 95% CI 3-7). Patients with RRSO uptake had higher odds of pancreatic (OR 2, 95% CI 1-2) or ovarian (OR 2, 95% CI 1-3) cancer family history and high-risk PGV (OR 6, 95% CI 4-8) and lower odds of Medicare (OR 0.4, 95% CI 0.2-0.8). Conclusions: Overall, the uptake of interventions was higher in patients with high- compared to moderate-risk PGV. More research, however, is needed on the shared decision-making process, as uptake of BLM was relatively high in those with moderate-risk PGV, and uptake of surveillance measures was relatively low.[Table: see text]

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

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

Fertility Preservation in BRCA1/2 Germline Mutation Carriers: An Overview.

BRCA1 and BRCA2 mutations are responsible for a higher incidence of breast and ovarian cancer (from 55% up to 70% vs. 12% in the general population). If their functions have been widely investigated in the onset of these malignancies, still little is known about their role in fertility impairment. Cancer patients treated with antineoplastic drugs can be susceptible to their gonadotoxicity and, in women, some of them can induce apoptotic program in premature ovarian follicles, progressive depletion of ovarian reserve and, consequently, cancer treatment-related infertility (CTRI). BRCA variants seem to be associated with early infertility, thus accelerating treatment impairment of ovaries and making women face the concrete possibility of an early pregnancy. In this regard, fertility preservation (FP) procedures should be discussed in oncofertility counseling-from the first line of prevention with risk-reducing salpingo-oophorectomy (RRSO) to the new experimental ovarian stem cells (OSCs) model as a new way to obtain in vitro-differentiated oocytes, several techniques may represent a valid option to BRCA-mutated patients. In this review, we revisit knowledge about BRCA involvement in lower fertility, pregnancy feasibility, and the fertility preservation (FP) options available.

Long-term bone health in women with a premenopausal risk-reducing salpingo-oophorectomy (RRSO) compared with women who underwent

Long-term bone health in women with a premenopausal risk-reducing salpingo-oophorectomy (RRSO) compared with women who underwent