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Background: Risk-reducing salpingo-oophorectomy (RRSO) is the gold standard method of ovarian cancer risk reduction, but the data are conflicting regarding the impact on breast cancer (BC) outcomes. This study aimed to quantify BC risk/mortality in BRCA1/BRCA2 carriers after RRSO. Methods: We conducted a systematic review (CRD42018077613) of BRCA1/BRCA2 carriers undergoing RRSO, with the outcomes including primary BC (PBC), contralateral BC (CBC) and BC-specific mortality (BCSM) using a fixed-effects meta-analysis, with subgroup analyses stratified by mutation and menopause status. Results: RRSO was not associated with a significant reduction in the PBC risk (RR = 0.84, 95%CI: 0.59–1.21) or CBC risk (RR = 0.95, 95%CI: 0.65–1.39) in BRCA1 and BRCA2 carriers combined but was associated with reduced BC-specific mortality in BC-affected BRCA1 and BRCA2 carriers combined (RR = 0.26, 95%CI: 0.18–0.39). Subgroup analyses showed that RRSO was not associated with a reduction in the PBC risk (RR = 0.89, 95%CI: 0.68–1.17) or CBC risk (RR = 0.85, 95%CI: 0.59–1.24) in BRCA1 carriers nor a reduction in the CBC risk in BRCA2 carriers (RR = 0.35, 95%CI: 0.07–1.74) but was associated with a reduction in the PBC risk in BRCA2 carriers (RR = 0.63, 95%CI: 0.41–0.97) and BCSM in BC-affected BRCA1 carriers (RR = 0.46, 95%CI: 0.30–0.70). The mean NNT = 20.6 RRSOs to prevent one PBC death in BRCA2 carriers, while 5.6 and 14.2 RRSOs may prevent one BC death in BC-affected BRCA1 and BRCA2 carriers combined and BRCA1 carriers, respectively. Conclusions: RRSO was not associated with PBC or CBC risk reduction in BRCA1 and BRCA2 carriers combined but was associated with improved BC survival in BC-affected BRCA1 and BRCA2 carriers combined and BRCA1 carriers and a reduced PBC risk in BRCA2 carriers.

Background: Risk-reducing mastectomy (RRM) and risk-reducing salpingo-oophorectomy (RRSO) are the most effective breast and ovarian cancer preventive interventions. EQ-5D is the recommended tool to assess the quality of life and determine health-related utility scores (HRUSs), yet there are no published EQ-5D HRUSs after these procedures. These are essential for clinicians counselling patients and for health-economic evaluations. Methods: We used aggregate data from our published systematic review and converted SF-36/SF-12 summary scores to EQ-5D HRUSs using a published mapping algorithm. Study control arm or age-matched country-specific reference values provided comparison. Random-effects meta-analysis provided adjusted disutilities and utility scores. Subgroup analyses included long-term vs. short-term follow-up. Results: Four studies (209 patients) reported RRM outcomes using SF-36, and five studies (742 patients) reported RRSO outcomes using SF-12/SF-36. RRM is associated with a long-term (>2 years) disutility of −0.08 (95% CI −0.11, −0.04) (I2 31.4%) and a utility of 0.92 (95% CI 0.88, 0.95) (I2 31.4%). RRSO is associated with a long-term (>1 year) disutility of −0.03 (95% CI −0.05, 0.00) (I2 17.2%) and a utility of 0.97 (95% CI 0.94, 0.99) (I2 34.0%). Conclusions: We present the first HRUSs sourced from patients following RRM and RRSO. There is a need for high-quality prospective studies to characterise quality of life at different timepoints.

Unselected population-based personalised ovarian cancer (OC) risk assessments combining genetic, epidemiological and hormonal data have not previously been undertaken. We aimed to understand the attitudes, experiences and impact on the emotional well-being of women from the general population who underwent unselected population genetic testing (PGT) for personalised OC risk prediction and who received low-risk (<5% lifetime risk) results. This qualitative study was set within recruitment to a pilot PGT study using an OC risk tool and telephone helpline. OC-unaffected women ≥ 18 years and with no prior OC gene testing were ascertained through primary care in London. In-depth, semi-structured and 1:1 interviews were conducted until informational saturation was reached following nine interviews. Six interconnected themes emerged: health beliefs; decision making; factors influencing acceptability; effect on well-being; results communication; satisfaction. Satisfaction with testing was high and none expressed regret. All felt the telephone helpline was helpful and should remain optional. Delivery of low-risk results reduced anxiety. However, care must be taken to emphasise that low risk does not equal no risk. The main facilitators were ease of testing, learning about children’s risk and a desire to prevent disease. Barriers included change in family dynamics, insurance, stigmatisation and personality traits associated with stress/worry. PGT for personalised OC risk prediction in women in the general population had high acceptability/satisfaction and reduced anxiety in low-risk individuals. Facilitators/barriers observed were similar to those reported with genetic testing from high-risk cancer clinics and unselected PGT in the Jewish population.

Introduction/BackgroundRRS is the most-effective prevention for breast-cancer (BC) and ovarian-cancer (OC) in women with increased-risk. We aimed to assess the quality-of-life (QoL) impact of risk-reducing surgery (RRS) including risk-reducing-mastectomy (RRM), risk-reducing-salpingo-oophorectomy (RRSO) and risk-reducing early-salpingectomy and delayed-oophorectomy (RRESDO) through a systematic review and meta-analysis.MethodologyWe searched major databases until December 2021 following a prospective protocol (PROSPERO-CRD42022319782). Qualitative-synthesis was performed to identify the impact of RRS on various QoL outcomes. Fixed-effects meta-analysis was performed to obtain pooled estimates of QoL outcomes.ResultsThirty-one studies were included (N=4151 post-RRS vs. N=3905 controls). 12/12 studies post-RRM (N=944) reported unchanged general-health QoL, and 10/16 (N=1911) post-RRSO reported unchanged/improved general-health QoL despite short-term deficits (N=578). 13/16 studies (N=1602) showed affected sexual-function post-RRSO. Meta-analysis showed a reduction (-1.21[-1.53,-0.89]; N=3070) in sexual-pleasure and an increase (1.12[0.93,1.31]; N=1400) in sexual-discomfort using the Sexual-Activity-Questionnaire. HRT in pre-menopausal RRSO was associated (on meta-analysis) with an increase (1.16 [0.17, 2.15]; N=291) in sexual-pleasure and a decrease (-1.20 [-1.75, -0.65]; N=157) in sexual-discomfort. 4/10 studies post-RRM (N=236) showed impacted sexual-function, while 6/10 (N=572) showed stable sexual-function. 5/10 studies post-RRM (N=514) reported no body-image problems, whereas 5/10 (N=344) showed otherwise. 12/13 studies (N=1871) reported increased menopause symptoms post-RRSO with a reduction (-1.96 [-2.81, -1.10]; N=1745) in Functional-Assessment-of-Cancer-Therapy-Endocrine Subscale on meta-analysis. 5/5 studies (N=365) post-RRM and 8/10 (N=1223) post-RRSO reported unchanged/decreased cancer-related-distress. RRESDO (2 studies, N=413) resulted in better sexual-function and menopause-specific QoL.ConclusionRRM/RRSO reduced cancer-related distress with unaffected general-health QoL. Women/clinicians should be aware of the negative impact of sexual dysfunction and menopause related symptoms from RRSO, along-with potential detrimental impact of RRM on body-image. Early salpingectomy does not appear to increase sexual dysfunction or impact menopause symptoms and RRESDO may be a promising alternative to mitigate QoL-related risks.

Introduction/BackgroundRisk-reducing mastectomy (RRM) and salpingo-oophorectomy (RRSO) are the gold standard preventative strategies for women at high-risk of breast cancer (BC)/ovarian cancer (OC). Risk-reducing early-salpingectomy followed by delayed-oophorectomy (RRESDO) is being trialled as an alternative to RRSO. Opportunistic bilateral salpingectomy (OBS) during gynaecological surgery has been proposed as a potential approach to prevent OC in general population. We performed a systematic review of the published evidence on cost-effectiveness of RRM/RRSO/RRESDO for BC/OC prevention in intermediate/high-risk women, and OBS in baseline-risk.MethodologyWe searched major databases to December 2021. We included economic evaluation studies reporting on cost-effectiveness/cost-utility outcomes in women at high-risk of BC/OC undergoing RRM/RRSO/RRESDO, or baseline OC risk undergoing OBS.ResultsOur search yielded 5801 citations; 22 studies were included. Eight studies concluded that RRM/RRSO individually or in combination were cost-effective compared to surveillance/no surgery for unaffected BRCA1/2 carriers, while one study found that RRESDO was cost-effective. Two studies on women at low/intermediate OC-risk specified that RRSO was cost-effective at OC lifetime risks of ≥4% (pre-menopausal) and ≥5% (post-menopausal women). These results were partially sensitive to initial age, uptake rates, cancer risk-reduction, and disutility following surgery. Four studies concluded that the addition of OBS to hysterectomy was cost-effective for OC prevention in the general population. Similarly, OBS was cost-effective as an alternative to sterilisation via laparoscopy (four studies) or at caesarean section (two studies). However, given the paucity of high-quality long-term outcome data, the uncertainty of level of risk-reduction, lack of disutility data, there remains some uncertainty around cost-effectiveness.ConclusionThis systematic review confirms that RRM/RRSO are cost-effective, and RRESDO is potentially cost-effective in women at intermediate/high risk of BC/OC in several high-income countries. Although OBS seems to be a potentially cost-effective option for OC risk-reduction, there is a need for high-quality evidence around its long-term including oncological outcomes.

Background/Objective: Platinum-resistant ovarian cancer (PROC) has limited therapeutic options, and the role of cytoreductive surgery (CRS) in improving survival outcomes remains uncertain. We performed a systematic review to evaluate the oncological benefit of CRS on PROC patients and the associated surgical morbidity and mortality. Methods: We followed a prospective protocol according to PRISMA guidelines. We searched PubMed, Medline, and Embase till October 2024. We used a “Population Intervention Comparator Outcomes (PICO)” framework. Our population included women with epithelial PROC who underwent CRS with/without chemotherapy. Our outcomes included overall survival (OS), progression-free-survival (PFS), post-operative morbidity and mortality and Quality of Life. Results: Our search yielded 6590 citations; six studies (N = 155 patients) were included. There is limited evidence available on the role of CRS in PROC, with notable variation in reported outcomes and outcomes’ measures; therefore, we were unable to perform quantitative synthesis. CRS demonstrated survival benefits in well-selected PROC patients, particularly those with limited, isolated recurrences, low tumour burden, and good performance status. Complete resection (R0) was associated with significantly longer OS/PFS compared to those who had suboptimal surgeries (R1/R2). Conclusions: CRS seems to extend survival in carefully selected PROC patients, especially those with limited disease spread and favourable surgical profiles. Nevertheless, CRS carries substantial surgical risks, and its benefits appear contingent upon achieving R0. Further prospective trials with standardised patient selection criteria are needed to define CRS’s role in PROC. At present, CRS in PROC should be considered within a multidisciplinary approach in specialised gynaecological oncology centres, with the careful assessment of patient-specific risk factors and potential for R0 resection.

Background1 in 40 UK Jewish individuals carry a pathogenic variant in BRCA1/BRCA2. Traditional testing criteria miss half of carriers, and so population genetic testing is being piloted for Jewish people in England. There has been no qualitative research into the factors influencing BRCA awareness and testing experience in this group. This study aimed to explore these and inform improvements for the implementation of population genetic testing.MethodsQualitative study of UK Jewish adults who have undergone BRCA testing. We conducted one-to-one semistructured interviews via telephone or video call using a predefined topic guide, until sufficient information power was reached. Interviews were audio-recorded, transcribed verbatim and interpreted using applied thematic analysis.Results32 individuals were interviewed (28 carriers, 4 non-carriers). We interpreted five themes intersecting across six time points of the testing pathway: (1) individual differences regarding personal/family history of cancer, demographics and personal attitudes/approach; (2) healthcare professionals’ support; (3) pathway access and integration; (4) nature of family/partner relationships; and (5) Jewish community factors. Testing was largely triggered by connecting information to a personal/family history of cancer. No participants reported decision regret, although there was huge variation in satisfaction. Suggestions were given around increasing UK Jewish community awareness, making information and support services personally relevant and proactive case management of carriers.ConclusionsThere is a need to improve UK Jewish community BRCA awareness and to highlight personal relevance of testing for individuals without a personal/family history of cancer. Traditional testing criteria caused multiple issues regarding test access and experience. Carriers want information and support services tailored to their individual circumstances.

Background: Risk-reducing hysterectomy (RRH) is the gold-standard prevention for endometrial cancer (EC). Knowledge of the impact on quality-of-life (QoL) is crucial for decision-making. This systematic review aims to summarise the evidence. Methods: We searched major databases until July 2022 (CRD42022347631). Given the paucity of data on RRH, we also included hysterectomy as treatment for benign disease. We used validated quality-assessment tools, and performed qualitative synthesis of QoL outcomes. Results: Four studies (64 patients) reported on RRH, 25 studies (1268 patients) on hysterectomy as treatment for uterine bleeding. There was moderate risk-of-bias in many studies. Following RRH, three qualitative studies found substantially lowered cancer-worry, with no decision-regret. Oophorectomy (for ovarian cancer prevention) severely impaired menopause-specific QoL and sexual-function, particularly without hormone-replacement. Quantitative studies supported these results, finding low distress and generally high satisfaction. Hysterectomy as treatment of bleeding improved QoL, resulted in high satisfaction, and no change or improvements in sexual and urinary function, although small numbers reported worsening. Conclusions: There is very limited evidence on QoL after RRH. Whilst there are benefits, most adverse consequences arise from oophorectomy. Benign hysterectomy allows for some limited comparison; however, more research is needed for outcomes in the population of women at increased EC-risk.

Policymakers require robust cost-effectiveness evidence of risk-reducing-surgery (RRS) for decision making on resource allocation for breast cancer (BC)/ovarian cancer (OC)/endometrial cancer (EC) prevention. We aimed to summarise published data on the cost-effectiveness of risk-reducing mastectomy (RRM)/risk-reducing salpingo-oophorectomy (RRSO)/risk-reducing early salpingectomy and delayed oophorectomy (RRESDO) for BC/OC prevention in intermediate/high-risk populations; hysterectomy and bilateral salpingo-oophorectomy (BSO) in Lynch syndrome women; and opportunistic bilateral salpingectomy (OBS) for OC prevention in baseline-risk populations. Major databases were searched until December 2021 following a prospective protocol (PROSPERO-CRD42022338008). Data were qualitatively synthesised following a PICO framework. Twenty two studies were included, with a reporting quality varying from 53.6% to 82.1% of the items scored in the CHEERS checklist. The incremental cost-effectiveness ratio/incremental cost-utility ratio and cost thresholds were inflated and converted to US$2020, using the original currency consumer price index (CPI) and purchasing power parities (PPP), for comparison. Eight studies concluded that RRM and/or RRSO were cost-effective compared to surveillance/no surgery for BRCA1/2, while RRESDO was cost-effective compared to RRSO in one study. Three studies found that hysterectomy with BSO was cost-effective compared to surveillance in Lynch syndrome women. Two studies showed that RRSO was also cost-effective at ≥4%/≥5% lifetime OC risk for pre-/post-menopausal women, respectively. Seven studies demonstrated the cost-effectiveness of OBS at hysterectomy (n = 4), laparoscopic sterilisation (n = 4) or caesarean section (n = 2). This systematic review confirms that RRS is cost-effective, while the results are context-specific, given the diversity in the target populations, health systems and model assumptions, and sensitive to the disutility, age and uptake rates associated with RRS. Additionally, RRESDO/OBS were sensitive to the uncertainty concerning the effect sizes in terms of the OC-risk reduction and long-term health impact. Our findings are relevant for policymakers/service providers and the design of future research studies.