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Objectives: To reduce the risk of ovarian cancer, BRCA1/2 mutation carriers are advised to undergo salpingo-oophorectomy (RRSO) around the age of 40 years. This may induce severe climacteric symptoms, potentially lowering their quality of life. Personal positive resources such as physical fitness and self-compassion may help women to deal with these symptoms. We investigated the association of climacteric symptoms with self-compassion and physical fitness in oophorectomized BRCA1/2 mutation carriers., Study Design: A cross-sectional study was conducted in 165 BRCA1/2 mutation carriers, aged 40-63 years, who underwent an RRSO at age 45 years or younger and at least 5 years previously., Main Outcome Measures: Climacteric symptoms were measured by the Greene Climacteric Scale. Self-compassion was rated using the Self-Compassion Scale-Short Form, and physical fitness using the Duke Activity Status Index., Results: BRCA1/2 mutation carriers reported low levels of climacteric symptoms (mean 10.28 [SD 6.45], and being highly self-compassionate and physically fit. After adjustment for possible covariates, higher self-compassion (β=-1.65, 95% CI -2.46, -0.84) and physical fitness (β=-0.25, 95% CI -0.34, -0.16) were associated with fewer climacteric symptoms. Current smoking was independently associated with more climacteric symptoms (β=2.66, 95% CI 0.26, 5.07)., Conclusions: Being self-compassionate and physically fit were associated with fewer climacteric symptoms. Future research is needed to investigate the effect of training in self-compassion and physical fitness on climacteric symptoms in BRCA1/2 mutation carriers., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: To identify influencing factors of BRCA1/2 mutation carriers and their professionals for risk-reducing salpingectomy (RRS) with delayed oophorectomy (RRO) as a substitute for risk-reducing salpingo-oophorectomy (RRSO) and for study participation on this concept., Methods: A qualitative study was performed by four focus group interviews with 39 BRCA1/2 mutation carriers and semi-structured in-depth interviews with 23 professionals in the field of hereditary cancer. We used a theoretical framework of determinants of innovation within healthcare organizations to classify influencing factors (barriers and facilitators)., Results: Among BRCA1/2 mutation carriers, main barriers for RRS with delayed RRO were seriousness of ovarian cancer, family history, and previous breast cancer. Among professionals, delay of risk-reducing effect of oophorectomy on breast cancer risk and a second operation were recognized as main barriers. Both BRCA1/2 mutation carriers and professionals found uncertainty about the effect of RRS with delayed RRO and ease of the decision to undergo RRSO important barriers. The main facilitator mentioned by both was longer maintenance of ovarian function thereby delaying negative effects of early surgical menopause. For study participation, BRCA1/2 mutation carriers mentioned a randomized study design as the main barrier, whereas professionals identified two facilitators, namely willingness of BRCA1/2 mutation carriers for study participation and uniform counseling. Furthermore, most BRCA1/2 mutation carriers and professionals were willing to consider participation in a future non-randomized study., Conclusions: We identified several barriers and facilitators for RRS with delayed RRO, and for study participation which can be addressed to optimize the design and implementation of a non-randomized study., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: Serum cancer antigen (CA) 125 is the only biomarker used frequently in women with or at risk for ovarian cancer. However, the same reference level is used before and after (prophylactic) bilateral salpingo-oophorectomy (BSO). We evaluated the effect of BSO on CA125 level in BRCA mutation carriers and tested which factors interact with the change in CA125 level., Methods: All women who participated in the Nijmegen gynecological screening program and underwent prophylactic BSO were included. Information was obtained on age, smoking, menopausal state, previous hysterectomy and breast cancer, histopathological examination of the adnexa, hormone therapy use, and CA125 level before and after surgical operation. Ovarian volume was calculated. The logarithmic-transformed CA125 levels were used in a linear mixed model to study the relative change in CA125 level and possible interaction., Results: In 60 women, a relative decrease of 18% in CA125 level after BSO was found (P < 0.01). The median serum CA125 level was 10.15 U/mL before and 8.36 U/mL after BSO. Menopausal state interacted with CA125 before and after the surgical operation (P < 0.01). In addition, ovarian volume did not explain the difference in CA125 level (P = 0.94)., Conclusions: BRCA mutation carriers show a relative decrease in CA125 level after BSO. Menopausal state interacts with CA125. Ovarian volume was excluded as a confounder. Possibly, the hormonal effect of ovaries plays a role in the CA125 level. Our study suggests that not the reference level of 35 U/mL but a lower level, as already suggested for postmenopausal women, should be applied to women after a salpingo-oophorectomy.

Women who carry a BRCA mutation have a greatly increased risk for serous ovarian carcinoma and tubal carcinoma. Since preventative ovarian screening is not effective, these women are advised to undergo prophylactic bilateral salpingo-oophorectomy (pBSO) around the age of 40 years. Following pBSO, hormone replacement therapy is advisable up to the age of 45-50 years, with the exception of those women with a history of breast cancer. The advice for women with a familial history of ovarian carcinoma but without the BRCA mutation is less clear. Based on data from the literature, we suggest considering pBSO only in women with at least two first or second degree family members with epithelial ovarian carcinoma. pBSO is not indicated in women from families without a BRCA mutation who have no family members, or just one family member, with epithelial ovarian carcinoma. In these families the lifetime risk for ovarian cancer is considered to be well below 10%.

Abstract: Background: BRCA1/2 mutation carriers’ choice between risk‐reducing salpingo‐oophorectomy (RRSO) and salpingectomy with delayed oophorectomy is very complex. Aim was to develop a patient decision aid that combines evidence with patient preferences to facilitate decision making. Design: Systematic development of a patient decision aid in an iterative process of prototype development, alpha testing by patients and clinicians and revisions using International Patient Decision Aid Standards (IPDAS) quality criteria. Information was based on the available literature and current guidelines. A multidisciplinary steering group supervised the process. Setting and participants: Pre‐menopausal BRCA1/2 mutation carriers choosing between RRSO and salpingectomy with delayed oophorectomy in Family Cancer Clinics in the Netherlands. Main outcome measures: IPDAS quality criteria, relevance, usability, clarity. Results: The patient decision aid underwent four rounds of alpha testing and revisions. Finally, two paper decision aids were developed: one for BRCA1 and one for BRCA2. They both contained a general introduction, three chapters and a step‐by‐step plan containing a personal value clarification worksheet. During alpha testing, risk communication and information about premature menopause and hormone therapy were the most revised items. The patient decision aids fulfil 37 of 43 (86%) IPDAS criteria for content and development process. Discussion and conclusions: Both BRCA1/2 mutation carriers and professionals are willing to use or offer the developed patient decision aids for risk‐reducing surgery. The patient decision aids have been found clear, balanced and comprehensible. Future testing among patients facing the decision should point out its effectiveness in improving decision making. [ABSTRACT FROM AUTHOR]

Background: Women with a BRCA1/2 pathogenic variant are advised to undergo premenopausal risk-reducing salpingo-oophorectomy after completion of childbearing, to reduce their risk of ovarian cancer. Several studies reported less sexual pleasure one to three years after a premenopausal oophorectomy. However, the long-term effects of a premenopausal oophorectomy on sexual functioning are unknown.Objective: Our aim was to study long-term sexual functioning in women at increased familial risk of breast/ovarian cancer who underwent a risk-reducing salpingo-oophorectomy either before the age of 46 years (premenopausal group), or after the age of 54 years (postmenopausal group). We performed subgroup analyses in the premenopausal group, comparing early (before the age of 41 years) and later (at ages 41-45 years) premenopausal risk-reducing salpingo-oophorectomy.Study Design: Between 2018 and 2021, we invited 817 women with a high familial risk of breast/ovarian cancer from an ongoing cohort study to participate in our study. Due to a large difference in age at study between the premenopausal and postmenopausal salpingo-oophorectomy groups, we restricted the comparison of sexual functioning between the groups to 368 women who were 60-70 years old at completion of the questionnaire (premenopausal group, n=226, postmenopausal group, n=142). In 496 women with a premenopausal risk-reducing salpingo-oophorectomy we compared sexual functioning between women in the early premenopausal group (n=151) and the later premenopausal group (n=345). Differences between groups were analyzed using multiple regression analyses adjusting for current age, breast cancer history, use of hormone replacement therapy, body mass index, chronic medication use (yes/no) and body image.Results: Mean time since risk-reducing salpingo-oophorectomy was 20.6 years in the premenopausal group and 10.6 years in the postmenopausal group (p-value <.001). In the premenopausal group, mean age at questionnaire completion was 62.7 years, versus 67.0 years in the postmenopausal group (p<.001). In the premenopausal group, 47.4% was still sexually active, compared to 48.9% of the postmenopausal group (p-value: .80). Current sexual pleasure scores were the same for women in the premenopausal group and the postmenopausal group (mean pleasure score 8.6, p-value .99). However, women in the premenopausal group more often reported substantial discomfort than women in the postmenopausal group (35.6% compared with 20.9%, p-value .04). After adjusting for confounders, premenopausal risk-reducing salpingo-oophorectomy was associated with substantially more discomfort during sexual intercourse, compared to postmenopausal risk-reducing salpingo-oophorectomy (odds ratio 3.1, 95% confidence interval 1.04; 9.4). Moreover, following premenopausal risk-reducing salpingo-oophorectomy, more severe complaints of vaginal dryness were observed (odds ratio 2.6, 95% confidence interval 1.4; 4.7). Women with a risk-reducing salpingo-oophorectomy before age 41 reported similar pleasure and discomfort scores as women with a risk-reducing salpingo-oophorectomy between ages 41 and 45.Conclusion: More than 15 years after premenopausal risk-reducing salpingo-oophorectomy, the proportion of sexually active women was comparable to that among women with a postmenopausal risk-reducing salpingo-oophorectomy. However, after a premenopausal risk-reducing salpingo-oophorectomy, women experienced more vaginal dryness and more often had substantial sexual discomfort during sexual intercourse. This did not lead to less pleasure with sexual activity. [ABSTRACT FROM AUTHOR]

Background: Risk-reducing salpingo-oophorectomy (RRSO) around the age of 40 is currently recommended to BRCA1/2 mutation carriers. This procedure decreases the elevated ovarian cancer risk by 80-96% but it initiates premature menopause as well. The latter is associated with short-term and long-term morbidity, potentially affecting quality of life (QoL). Based on recent insights into the Fallopian tube as possible site of origin of serous ovarian carcinomas, an alternative preventive strategy has been put forward: early risk-reducing salpingectomy (RRS) and delayed oophorectomy (RRO). However, efficacy and safety of this alternative strategy have to be investigated. Methods: A multicentre non-randomised trial in 11 Dutch centres for hereditary cancer will be conducted. Eligible patients are premenopausal BRCA1/2 mutation carriers after completing childbearing without (a history of) ovarian carcinoma. Participants choose between standard RRSO at age 35-40 (BRCA1) or 40-45 (BRCA2) and the alternative strategy (RRS upon completion of childbearing and RRO at age 40-45 (BRCA1) or 45-50 (BRCA2)). Women who opt for RRS but do not want to postpone RRO beyond the currently recommended age are included as well. Primary outcome measure is menopause-related QoL. Secondary outcome measures are ovarian/breast cancer incidence, surgery-related morbidity, histopathology, cardiovascular risk factors and diseases, and cost-effectiveness. Mixed model data analysis will be performed. Discussion: The exact role of the Fallopian tube in ovarian carcinogenesis is still unclear. It is not expected that further fundamental research will elucidate this role in the near future. Therefore, this clinical trial is essential to investigate RRS with delayed RRO as alternative risk-reducing strategy in order to improve QoL. [ABSTRACT FROM AUTHOR]

Objective: To estimate BRCA1/2 mutation carriers' cumulative ovarian cancer risks after risk-reducing salpingectomy at various ages with delayed oophorectomy several years later compared with risk-reducing salpingo-oophorectomy.Methods: A literature search was performed on cumulative ovarian cancer risks and effects of risk-reducing salpingo-oophorectomy and salpingectomy. Results were used in a modeling study to estimate cumulative ovarian cancer risks for various scenarios of salpingectomy with delayed oophorectomy and risk-reducing salpingo-oophorectomy using Cox proportional hazard models.Results: Estimated cumulative ovarian cancer risks at age 70 years for risk-reducing salpingectomy with delayed oophorectomy are highest for BRCA1 mutation carriers undergoing surgeries at higher age. Maximum increase in point estimates (from 1.8% to 4.1%) occurs in 40-year-old BRCA1 mutation carriers undergoing oophorectomy at age 45 years after nonprotective salpingectomy instead of salpingo-oophorectomy at age 40 years. In the best-case scenario, assuming 65% risk reduction by salpingectomy and 96% by salpingo-oophorectomy, point estimates increase (from 1.8% to 2.6%) or decrease (from 3.4% to 3.3%) depending on age. In the worst-case scenario for BRCA2, point estimates maximally increase from 0.6% to 1.8% in 45-year-old carriers when oophorectomy is performed at age 50 years instead of risk-reducing salpingo-oophorectomy at age 45 years. In the best-case scenario, point estimates increase (from 1.3% to 1.5%) or decrease (from 1.5 to 1.3%).Conclusion: Differences in estimated ovarian cancer risks between risk-reducing salpingo-oophorectomy and salpingectomy with delayed oophorectomy are small, even if salpingectomy is ineffective. Presented estimated ovarian cancer risks can be used in counseling BRCA1/2 mutation carriers, thereby facilitating a personalized and well-informed choice for either strategy. [ABSTRACT FROM AUTHOR]

Germline mutations in BRCA1 and BRCA2 genes were discovered twenty years ago. Female BRCA mutation carriers have an increased risk of breast and ovarian cancer at a relatively young age. Several choices have to be made with respect to cancer risk management, and consequences of these choices may affect quality of life. A review of the literature was performed to evaluate quality of life in unaffected BRCA mutation carriers and the influence of these medical choices. Overall, general quality of life appears not to be permanently affected in BRCA mutation carriers or by their choices. Risk-reducing salpingo-oophorectomy and its subsequent premature menopause affect (menopause specific) quality of life most. Hormone replacement therapy does not fully alleviate climacteric symptoms and therefore, there is a strong need for alternative strategies to reduce ovarian cancer risk and/or for improvements in postoperative care. Future research should focus on these needs. [ABSTRACT FROM AUTHOR]

Abstract: Objective: A precursor lesion for ovarian carcinoma, tubal intraepithelial carcinoma (TIC), has been identified in BRCA-mutation carriers undergoing prophylactic bilateral salpingo-oophorectomy (pBSO). Other lesions were also identified in fallopian tubes, but different terminology, interpretation, and lack of knowledge of normal epithelium, have hampered to unravel their possible role in carcinogenesis. The aim of this study is to classify tubal epithelial lesions in BRCA-mutation carriers and controls to enable comparison of prevalence, area of localization, and possible malignant potential. Methods: Two hundred twenty-six BRCA1/2-mutation carriers were included; ovaries and fallopian tubes, embedded completely, were reviewed. Controls included 105 women who underwent BSO for non-malignant reasons. Tubal epithelial lesions included the following categories: hyperplasia, minor epithelial atypia, TIC, and invasive carcinoma. Results: Tubal neoplasia was identified in 7.1% (invasive carcinoma, 0.9%; TIC, 6.2%) of BRCA-mutation carriers compared to none in controls (p =0.004, Fisher''s exact test). Hyperplasia and minor epithelial atypia were identified in 41.6% BRCA-mutation carriers and compared to 58.1% in controls (p =0.005, Pearson''s chi square). Invasive carcinoma and TIC showed preference for the fimbrial ends (p =0.027, Pearson''s chi square), while hyperplasia and minor epithelial atypia displayed more variation in localization. Conclusions: Invasive tubal carcinoma and TIC were limited to BRCA-mutation carriers, whereas hyperplasia and minor epithelial atypia were commonly found in both BRCA-mutation carriers and controls. It is suggested that hyperplasia and minor atypia represent variations of normal tubal epithelium instead of premalignant lesions. Furthermore, total salpingectomy is strongly recommended as most but not all TIC occurred in the fimbriae. [Copyright &y& Elsevier]