Cost-Effectiveness of Gene-Specific Prevention Strategies for Ovarian and Breast Cancer.

Importance: Pathogenic variants (PVs) in BRCA1, BRCA2, PALB2, RAD51C, RAD51D, and BRIP1 cancer susceptibility genes (CSGs) confer an increased ovarian cancer (OC) risk, with BRCA1, BRCA2, PALB2, RAD51C, and RAD51D PVs also conferring an elevated breast cancer (BC) risk. Risk-reducing surgery, medical prevention, and BC surveillance offer the opportunity to prevent cancers and deaths, but their cost-effectiveness for individual CSGs remains poorly addressed. Objective: To estimate the cost-effectiveness of prevention strategies for OC and BC among individuals carrying PVs in the previously listed CSGs. Design, Setting, and Participants: In this economic evaluation, a decision-analytic Markov model evaluated the cost-effectiveness of risk-reducing salpingo-oophorectomy (RRSO) and, where relevant, risk-reducing mastectomy (RRM) compared with nonsurgical interventions (including BC surveillance and medical prevention for increased BC risk) from December 1, 2022, to August 31, 2023. The analysis took a UK payer perspective with a lifetime horizon. The simulated cohort consisted of women aged 30 years who carried BRCA1, BRCA2, PALB2, RAD51C, RAD51D, or BRIP1 PVs. Appropriate sensitivity and scenario analyses were performed. Exposures: CSG-specific interventions, including RRSO at age 35 to 50 years with or without BC surveillance and medical prevention (ie, tamoxifen or anastrozole) from age 30 or 40 years, RRM at age 30 to 40 years, both RRSO and RRM, BC surveillance and medical prevention, or no intervention. Main Outcomes and Measures: The incremental cost-effectiveness ratio (ICER) was calculated as incremental cost per quality-adjusted life-year (QALY) gained. OC and BC cases and deaths were estimated. Results: In the simulated cohort of women aged 30 years with no cancer, undergoing both RRSO and RRM was most cost-effective for individuals carrying BRCA1 (RRM at age 30 years; RRSO at age 35 years), BRCA2 (RRM at age 35 years; RRSO at age 40 years), and PALB2 (RRM at age 40 years; RRSO at age 45 years) PVs. The corresponding ICERs were -£1942/QALY (-$2680/QALY), -£89/QALY (-$123/QALY), and £2381/QALY ($3286/QALY), respectively. RRSO at age 45 years was cost-effective for RAD51C, RAD51D, and BRIP1 PV carriers compared with nonsurgical strategies. The corresponding ICERs were £962/QALY ($1328/QALY), £771/QALY ($1064/QALY), and £2355/QALY ($3250/QALY), respectively. The most cost-effective preventive strategy per 1000 PV carriers could prevent 923 OC and BC cases and 302 deaths among those carrying BRCA1; 686 OC and BC cases and 170 deaths for BRCA2; 464 OC and BC cases and 130 deaths for PALB2; 102 OC cases and 64 deaths for RAD51C; 118 OC cases and 76 deaths for RAD51D; and 55 OC cases and 37 deaths for BRIP1. Probabilistic sensitivity analysis indicated both RRSO and RRM were most cost-effective in 96.5%, 89.2%, and 84.8% of simulations for BRCA1, BRCA2, and PALB2 PVs, respectively, while RRSO was cost-effective in approximately 100% of simulations for RAD51C, RAD51D, and BRIP1 PVs. Conclusions and Relevance: In this cost-effectiveness study, RRSO with or without RRM at varying optimal ages was cost-effective compared with nonsurgical strategies for individuals who carried BRCA1, BRCA2, PALB2, RAD51C, RAD51D, or BRIP1 PVs. These findings support personalizing risk-reducing surgery and guideline recommendations for individual CSG-specific OC and BC risk management.

Long-term risk of adnexal operation after vaginal hysterectomy for pelvic organs prolapse repair.

OBJECTIVE: To determine if women who undergo vaginal hysterectomy for pelvic floor prolapse repair without concomitant opportunistic bilateral salpingo-oophorectomy are at increased risk of further complications related to the remaining adnexa later in life. STUDY DESIGN: The database of a tertiary university medical center was searched for all women who underwent vaginal hysterectomy as part of the treatment for pelvic organ prolapse, without opportunistic adnexectomy, from 2006 to 2015 to provide adequate time for long-term evaluation. Demographic and clinical data including surgeries performed during the long-term follow-up were collected from all medical insurer electronic medical records. RESULTS: The cohort included 427 women of mean age 63 ± 9.3 years; 90.9 % were postmenopausal. Mean duration of follow-up was 10.7 ± 2.6 years. During the follow-up period, only 3 patients (0.7 %) were re-operated for left adnexal pathology, non-malignant in all cases. CONCLUSION: In women undergoing vaginal hysterectomy for pelvic organ prolapse without opportunistic adnexectomy, preservation of the adnexa poses only a very low risk for adnexal pathology or need for reoperation later in life.

The Concept behind the Suitability of Menstrual Blood-Derived Stem Cells for the Management of Vaginal Atrophy among BRCA Mutation Carriers after RRSO.

Risk-reducing bilateral salpingo-oophorectomy (RRSO) is recommended for breast cancer gene 1 (BRCA1) and 2 (BRCA2) mutation carriers. A major consequence of RRSO is surgical menopause associated with severe menopausal symptoms, mostly genitourinary complaints. Due to the inherent breast cancer risk, estrogen-based therapies are generally avoided in these patients. So far, the non-hormonal approaches available are not efficient to successfully treat the disabling vaginal atrophy-related symptoms. In regenerative medicine, mesenchymal stem cells (MSC) are the most frequently used cell type due to their remarkable and regenerative characteristics. Therapies based on MSC have revealed positive outcomes regarding symptoms and signs associated with vaginal atrophy by promoting angiogenesis, vaginal restoration, and the proliferation of vaginal mucosa cells. Menstrual blood-derived stem cells (MenSC) are a novel source of MSC, with promising therapeutic potential directly linked to their high proliferative rates; low immunogenicity; non-invasive, easy, and periodic acquisition; and almost no associated ethical issues. In this review, we update the current knowledge and research regarding the potential value of previously preserved MenSC in the therapy of vaginal atrophy among BRCA mutation carriers subjected to RRSO.

Long-term outcomes of hysterectomy with bilateral salpingo-oophorectomy: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to provide an up-to-date systematic review of "the long-term outcomes of bilateral salpingo-oophorectomy at the time of hysterectomy" and perform a meta-analysis for the reported associations. DATA SOURCES: Our study updated a previous systematic review by searching the literature using PubMed, Web of Science, and Embase for publications between January 2015 and August 2022. STUDY ELIGIBILITY CRITERIA: Our study included studies of women who had a hysterectomy with bilateral salpingo-oophorectomy vs women who had a hysterectomy with ovarian conservation or no surgery. METHODS: The quality of the evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations. Adjusted hazard ratios were extracted and combined to obtain fixed effect estimates. RESULTS: Compared with hysterectomy or no surgery, hysterectomy with bilateral salpingo-oophorectomy in young women was associated with decreased risk of breast cancer (hazard ratio, 0.78; 95% confidence interval, 0.73-0.84) but with an increased risk of colorectal cancer (hazard ratio, 1.27; 95% confidence interval, 1.10-1.47). In addition, it was associated with an increased risk of total cardiovascular diseases, coronary heart disease, and stroke with hazard ratios of 1.18 (95% confidence interval, 1.11-1.25), 1.17 (95% confidence interval, 1.10-1.25), and 1.20 (95% confidence interval, 1.10-1.31), respectively. Compared with no surgery, hysterectomy with bilateral salpingo-oophorectomy before the age of 50 years was associated with an increased risk of hyperlipidemia (hazard ratio, 1.44; 95% confidence interval, 1.25-1.65), diabetes mellitus (hazard ratio, 1.16; 95% confidence interval, 1.09-1.24), hypertension (hazard ratio, 1.13; 95% confidence interval, 1.06-1.20), dementia (hazard ratio, 1.70; 95% confidence interval, 1.07-2.69), and depression (hazard ratio, 1.39; 95% confidence interval, 1.22-1.60). The evidence on the association with all-cause mortality in young women showed substantial heterogeneity between the studies (I2=85%; P<.01). CONCLUSION: Hysterectomy with bilateral salpingo-oophorectomy was associated with multiple long-term outcomes. The benefits of the addition of bilateral salpingo-oophorectomy to hysterectomy should be balanced against the risks.

Risk-reducing decisions regarding germline BRCA pathogenic variant: focusing on the timing of genetic testing and RRSO.

BACKGROUND: In Japan, the public insurance policy was revised in 2020 to cover hereditary breast and ovarian cancer (HBOC), including genetic testing and surveillance, for patients with breast cancer (BC). Consequently, the demand for risk-reducing salpingo-oophorectomy (RRSO) has increased. This study aimed to clarify the changes in the demand and timing of genetic testing and RRSO associated with public insurance coverage for HBOC in Japan. METHODS: This retrospective analysis included 350 women with germline BRCA (gBRCA) pathogenic variants (PVs) who had visited gynaecologists; they received gBRCA genetic testing at 45.1±10.6 (20-74) years. The use of medical testing and preventive treatment was compared between the preinsurance and postinsurance groups using Mann-Whitney U and Fisher's exact tests. RESULTS: The findings indicate that RRSO rates doubled from 31.4% to 62.6% among patients with gBRCA-PV. The implementation rate was 32.4% among unaffected carriers and 70.3% among BC-affected patients. Younger patients received genetic testing with significantly shorter intervals between BC diagnosis and genetic testing and between genetic testing and RRSO. CONCLUSION: Overall, the insurance coverage for HBOC patients with BC has increased the frequency of RRSO in Japan. However, a comparison between the number of probands and family members indicated that the diagnosis among family members is inadequate. The inequality in the use of genetic services by socioeconomic groups is an issue of further concern.

Quality of life after risk-reducing salpingo-oophorectomy in women with a pathogenic BRCA variant.

BACKGROUND: Risk-reducing salpingo-oophorectomy (RRSO) is recommended to women with a pathogenic BRCA variant, but as a main side effect, RRSO could lead to an early onset of menopause. AIM: To evaluate the impact of RRSO and preoperative menopausal status on menopausal symptoms, sexual functioning, and quality of life (QOL). METHODS: The study was conducted between November 2019 and April 2020. Women were included who tested positive for a pathogenic BRCA1/2 variant between 2015 and 2018. Depression levels, QOL, and global health status were measured and compared with those of women who opted against RRSO. Furthermore, women who underwent RRSO treatment were asked to report menopausal complaints that they experienced at 1 month postsurgery and any current complaints. OUTCOMES: RRSO had no significant impact on QOL, but women who were premenopausal at the time of surgery reported more sexual complaints than postmenopausal women. RESULTS: In total, 134 carriers of a BRCA mutation were included: 90 (67%) underwent RRSO and 44 (33%) did not. At the time of the survey, neither the control nor experimental group experienced significant changes in QOL (b = -0.18, P = .59). Women who underwent RRSO reported a significantly lower global health status (b = -0.66, P = .05). Women who were premenopausal at the time of surgery were bothered more by sexual symptoms (b = 0.91, P = .19) but experienced fewer vasomotor complaints (b = -1.09, P = .13) than women who were postmenopausal at the time of RRSO. CLINICAL IMPLICATIONS: The decrease of sexual functioning after RRSO should be an integral part of preoperative counseling because it is important for BRCA carriers, especially for premenopausal women. STRENGTHS AND LIMITATIONS: Some strengths of the present study were the long follow-up, a high response rate, and the existence of a control group, whereas defining menopausal status by last menstrual bleeding and self-report of data (eg, breast cancer history) increased the risk of errors. CONCLUSION: Our study indicated that women who underwent RRSO experienced no difference in QOL when compared with women without RRSO and that patients with premenopausal status seemed to be at higher risk to experience sexual complaints after surgery.

Concurrent uterine surgery and uptake of hormone therapy in patients undergoing bilateral salpingo-oophorectomy for risk-reducing or therapeutic indications.

OBJECTIVE: This study aimed to analyze factors associated with concurrent uterine surgery in patients undergoing bilateral salpingo-oophorectomy (BSO) for risk reducing or therapeutic purposes. Additionally, trends in surgical choice and uptake of post-operative hormone therapy (HT) were examined. METHODS: A 10-year retrospective study was conducted on patients who underwent risk-reducing or therapeutic BSO at one institution. Multinomial regression analysis of patient and case characteristics was performed evaluating associations with surgery type (BSO, BSO and hysterectomy, or BSO and endometrial sampling). Trends in surgery type and uptake of HT post operatively are described. RESULTS: Among the study sample of 643 patients, 140 (22%) patients underwent therapeutic BSO for a history of hormone receptor (HR) positive breast cancer, while the remainder underwent risk-reducing BSO due to a pathogenic variant and/or family history. Pathogenic variants included BRCA1 (141, 40%) BRCA2 (173, 49%), and Lynch syndrome genes (15, 4%). Regression analysis revealed significant associations between concurrent hysterectomy and Black race (RR = 3.55, CI = 1.51-8.38, p = 0.004), history of HR positive breast cancer (RR = 1.88, CI = 1.03-3.42, p = 0.04), and surgeon (Surgeon 1, RR = 2.43, CI = 1.36-4.35, p = 0.003). Among eligible patients under age 51, 36% initiated HT. Over the study period, concurrent hysterectomy rates declined while endometrial sampling increased. CONCLUSIONS: Rates of hysterectomy declined over the study period and slightly more than one-third of eligible patients utilized post-operative HT. Further research on concurrent uterine surgery is needed to establish standardized treatment recommendations in the risk-reducing and therapeutic BSO population. Additionally, education regarding the benefits of postoperative HT in eligible patients is warranted.

Combined Bilateral Salpingo-oophorectomy and Cesarean Delivery in BRCA1/2 Alteration Carriers : A Case Series.

BACKGROUND: The cumulative lifetime risk of ovarian cancer is 16-68% and 11-30% in female BRCA1 and BRCA2 gene alteration carriers, respectively. Risk-reducing bilateral salpingo-oophorectomy (RRSO) is the only proven way to reduce ovarian cancer mortality. We report a series of patients who underwent risk-reducing surgery at the time of planned obstetric-indicated cesarean delivery. CASES: This is a case series of four women carrying a pathogenic germline BRCA1 or BRCA2 gene alteration who underwent RRSO at the time of cesarean delivery between March 1, 2018, and March 31, 2022. All women were referred during pregnancy to the University College London Hospitals Familial Cancer Clinic for consideration of RRSO at the time of obstetric-indicated cesarean delivery. Women were considered eligible for RRSO if they had a proven pathogenic germline alteration, would have completed childbearing after the cesarean delivery, and were older than age 35 or 40 years with BRCA1 or BRCA2 alterations, respectively. Operating time, blood loss, transfusion requirements, length of hospital stay, complications, and ability to breastfeed were assessed and, where possible, compared with the institutional means for similar patients who underwent cesarean delivery only, to determine whether RRSO was associated with increased morbidity. Women were contacted 11-59 months postprocedure to assess satisfaction. The mean blood loss was 687 mL (range 400-1,000 mL), mean operating time was 68 minutes, mean length of hospital stay was 3 days, and mean change in hemoglobin was -1 g/dL. No patient required a transfusion, had internal organ damage, returned to the operating room, or was readmitted. One of two women with intact breast tissue successfully breastfed, and the other chose to bottle feed. The mean contemporaneous institutional blood loss for cesarean delivery was not significantly different at 681 mL for singleton pregnancies and 872 mL for twin pregnancies. All four women reported a high level of satisfaction with the combined procedure. CONCLUSION: Our results show that RRSO can be performed at the time of cesarean delivery with high patient satisfaction. This approach can be offered to appropriately counseled individuals, with the benefit of avoiding the need for two separate procedures, with potentially reduced patient morbidity and health care costs.

Prophylactic Salpingo-Oophorectomy and Survival After BRCA1/2 Breast Cancer Resection.

Importance: Few studies have investigated whether prophylactic salpingo-oophorectomy (PSO) for patients with previously resected breast cancer who carry pathogenic germline BRCA1 or BRCA2 variants is associated with a reduced risk of cancer-specific death. Objective: To assess the association of PSO and prophylactic mastectomy (PM) with prognosis after quadrantectomy or mastectomy as primary treatment for patients with BRCA1 or BRCA2 breast cancer. Design, Setting, and Participants: This retrospective cohort study was performed in a single-institution, tertiary referral center. Consecutive patients with invasive breast cancer treated surgically between 1972 and 2019 were recruited and followed up prospectively after they were found to carry the BRCA1 or BRCA2 gene variant. The data analysis was performed between April 2022 and July 2023. Exposure: Following breast surgery, some patients underwent PSO, PM, or both, whereas others did not. Main Outcomes and Measures: The primary study end point was overall survival as measured by the Kaplan-Meier method. Secondary end points were crude cumulative incidence of breast cancer-specific mortality, ipsilateral breast tumor recurrence (IBTR), contralateral breast cancer, ovarian cancer, and ovarian cancer-specific mortality. Results: Of 480 patients included in the cohort (median age at initial surgery, 40.0 years; IQR, 34.0-46.0 years), PSO was associated with a significantly reduced risk of death (hazard ratio [HR], 0.40; 95% CI, 0.25-0.64; P < .001). This reduction was most evident for patients carrying the BRCA1 variant (HR, 0.35; 95% CI, 0.20-0.63; P = .001), those with triple-negative disease (HR, 0.21; 95% CI, 0.09-0.46; P = .002), and those with invasive ductal carcinoma (HR, 0.51; 95% CI, 0.31-0.84; P = .008). Prophylactic salpingo-oophorectomy was not associated with risk of contralateral breast cancer or IBTR. Initial or delayed PM was associated with a reduced risk of IBTR but not with overall survival or breast cancer-specific mortality. Conclusions: The study findings suggest that PSO should be offered to all patients with BRCA1/2 breast cancer who undergo surgery with curative intent to reduce risk of death. In particular, PSO should be offered to patients with the BRCA1 variant at the time of breast surgery.

Low-grade appendiceal mucinous neoplasm encountered during risk-reducing salpingo-oophorectomy: A case of laparoscopic surgery.

Low-grade appendiceal mucinous neoplasm (LAMN) is a rare epithelial malignancy of the appendix. If it perforates the abdominal cavity, it can cause a serious clinical syndrome called pseudomyxoma peritonei. In the present case, we laparoscopically removed a LAMN encountered during risk-reducing salpingo-oophorectomy (RRSO). The patient was a 53-year-old woman who was diagnosed with hereditary breast and ovarian cancer syndrome. RRSO was planned, and magnetic resonance imaging revealed a large cystic tumor in the right lower abdomen. We expected an ovarian cyst; however, it was a primary tumor of the appendix. Partial cecal resection was performed laparoscopically by a surgical oncologist. The pathological diagnosis was LAMN. Gynecologists may encounter this disease incidentally. Mucinous appendiceal neoplasm (MAN) may be encountered during RRSO. If a right lower abdominal mass is found near a normal ovary preoperatively, gynecologists should consider MAN as well as paraovarian cyst.

Acute Large Ovarian Cyst After Surgical Resection of Juvenile Granulosa Cell Tumor Stage 1C.

Juvenile granulosa cell tumors (JGCTs) are rare, though carry significant burden of morbidity and mortality. A 15-year-old menstruating female with abdominal pain was diagnosed with a large 22.3 cm pelvic mass. CA-125 and LDH were elevated. Exploratory laparotomy was undertaken due to lesion size, and left salpingo-oophorectomy with omentectomy was completed. Pathology confirmed JGCTs with focal disruption, consistent with Stage IC disease. Six weeks postoperatively, the patient experienced recurrent abdominal pain and ultrasound revealed a 7.9 cm right ovarian cystic structure. Given size and nodularity, management was discussed with a multidisciplinary team. Serial ultrasounds demonstrated resolution of the cyst. Workup for ovarian masses in pediatric patients has added complexity of fertility preservation. Once ovarian torsion is ruled out, imaging and laboratory studies are completed to characterize the mass. In pediatric patients with cancer of the Mullerian structures and risk of infertility, decision-making can be challenging and is best managed with a multidisciplinary approach.

Subjective cognitive changes following premenopausal risk-reducing bilateral salpingo-oophorectomy.

OBJECTIVE: Women at high risk of ovarian cancer are commonly advised to undergo risk-reducing bilateral salpingo-oophorectomy (BSO) prior to natural menopause. Cognitive symptoms during natural menopause transition are frequently reported; however, very few studies have examined cognitive changes following surgical menopause. To address this gap, we explored the cognitive experiences of women within 24 months post BSO. METHODS: This observational cross-sectional sub-study is part of a larger project, the Early Menopause and Cognition Study (EM-COG). We investigated perceived cognitive experiences in Australian women (n = 16) who underwent risk-reducing BSO using qualitative interviews. Thematic analysis was undertaken to identify key themes. RESULTS: Fifteen out of 16 participants (93.75%) reported changes to cognition within 24 months post BSO. The key cognitive symptoms reported were brain fog, memory and retrieval difficulties, slower processing speed as well as attention difficulties. Five participants (31.3%) experienced negative mood symptoms post BSO. CONCLUSION: Findings from this study suggest that women experience subjective cognitive changes within 24 months post BSO. This period could be a vulnerable time for women's cognitive health. While these findings need to be confirmed by a large prospective study, our research indicates that psychoeducation and awareness will be helpful in managing cognitive symptoms after surgical menopause.

Menopausia quirúrgica en pacientes con mutación BRCA, el papel de la terapia hormonal / Surgical Menopause in Patients with BRCA Mutation, the Role of Hormone Therapy

Introducción: las mujeres con mutación BRCA1/2 (mBRCA) tienen un riesgo aumentado de desarrollar cáncer de mama (CM) y ovario (CO). La salpingo-oforectomía bilateral (SOB) se asocia con la reducción del riesgo del 80% para CO y un 50% para CM. Se recomienda realizarla entre los 35 y 40 años. Como consecuencia se produce una menopausia prematura, con un impacto negativo sobre la calidad de vida por la presencia de síntomas climatéricos, aumento del riesgo de enfermedad cardiovascular, osteoporosis y riesgo de alteración cognitiva. La terapia hormonal (THM) es el tratamiento más eficaz para la prevención de estos síntomas. Estado del arte: distintos estudios han demostrado un mayor riesgo de CM en mujeres posmenopáusicas que reciben THM en particular con terapia combinada, estrógeno + progesterona (E+P). Según el metanálisis de Marchetti y cols., en las mujeres portadoras de mBRCA que recibieron THM, no hubo diferencias en el riesgo de CM comparando E solo con E+P. En el estudio de Kotsopoulos, incluso se encontró un posible efecto protector en aquellas que usaron E solo. Otro estudio en portadoras sanas demostró que, en las mujeres menores de 45 años al momento de la SOB, la THM no afectó las tasas de CM. Sin embargo, en las mujeres mayores de 45 años, las tasas de CM fueron más altas. Como el esquema de E+P se asocia con un mayor riesgo relativo (RR) de CM, las dosis de progestágenos utilizados se deberían limitar, eligiendo derivados naturales de progesterona, de uso intermitente para disminuir la exposición sistémica. Según diferentes guías internacionales, a las portadoras de mBRCA sanas que se someten a una SOB se les debe ofrecer THM hasta la edad promedio de la menopausia. Conclusión: la menopausia prematura disminuye la expectativa de vida; es por ello que una de las herramientas para mejorar y prevenir el deterioro de la calidad de vida es la THM. El uso de THM a corto plazo parece seguro para las mujeres portadoras de mBRCA que se someten a una SOB antes de los 45 años, al no contrarrestar la reducción del riesgo de CM obtenida gracias a la cirugía. (AU)

Introduction: women with BRCA1/2 (mBRCA) mutation have an increased risk of developing breast (BC) and ovarian (OC) cancer. Bilateral salpingo-oophorectomy (BSO) is associated with an 80% risk reduction for OC and 50% for BC. The recommended age for this procedure is 35 to 40 years. The consequence is premature menopause, which hurts the quality of life due to the presence of climacteric symptoms, increased risk of cardiovascular disease, osteoporosis, and a higher risk of cognitive impairment. Hormone therapy (MHT) is the most effective treatment for preventing these symptoms. State of the art: different studies have shown an increased risk of BC in postmenopausal women receiving MHT, particularly with combined therapy, estrogen + progesterone (E+P). According to the meta-analysis by Marchetti et al., in women carrying mBRCA who received MHT, there was no difference in the risk of BC compared to E alone with E+P. In the Kostopoulos study, there was also a possible protective effect in those who used E alone. Another study in healthy carriers showed that in women younger than 45 years at the time of BSO, MHT did not affect BC rates. However, in women older than 45 years, BC rates were higher. As the E+P scheme is associated with a higher RR of BC, the doses of progestogens should be limited, choosing natural progesterone byproducts of intermittent use to decrease systemic exposure. According to various international guidelines, healthy mBRCA carriers undergoing BSO should be offered MHT until the average age of menopause. Conclusion: premature menopause decreases life expectancy, which is why one of the tools to improve and prevent deterioration of quality of life is MHT. Short-term use of MHT appears safe for women with mBRCA who undergo BSO before age 45 as it does not counteract the reduction in the risk of MC obtained by surgery. (AU)

Theory-based behavior change intervention to increase uptake of risk-reducing salpingo-oophorectomy in women with a BRCA1 or BRCA2 pathogenic variant: The PREVENT randomized controlled trial.

OBJECTIVE: To evaluate the effect of a theory-based behavioral intervention delivered by genetic counselors on the uptake of risk-reducing salpingo-oophorectomy (RRSO) at 12 and 24 months by women with a BRCA1 or BRCA2 pathogenic variant (PV) compared to women who received usual care. METHODS: In this two-arm, multi-site randomized controlled trial participants were randomized to receive a theoretically-guided behavioral telephone intervention or usual care. Outcome data were collected at 12 and 24 months. Participants in the usual care arm were offered the intervention after 12 months. RESULTS: Data on 107 participants were included in the analysis. There was no significant difference in the proportion of women who had a RRSO by 1 year (28.6%- intervention; 22.9%- usual care (p = 0.54)). At 1 year, women who received the intervention had significantly lower mean decisional conflict (pinteraction <0.001) and a higher mean knowledge score at one-year compared to usual care (pinteraction <0.001). At 2 years, 53.9% of participants in the intervention arm had RRSO compared to 32.6% in usual care (p = 0.05). CONCLUSIONS: A theory-based behavioral intervention delivered by genetic counselors to women with a BRCA PV who chose not to have the recommended RRSO was effective at reducing decisional conflict and increasing knowledge in women with a BRCA1 or BRCA2 PV.

Pathological findings and long-term prognosis in Korean BRCA1/2 mutation carriers undergoing risk-reducing salpingo-oophorectomy.

OBJECTIVE: Our study aimed to evaluate the incidence of pathological findings in asymptomatic Korean patients with BRCA1/2 pathogenic variants who underwent risk-reducing salpingo-oophorectomy and to assess their long-term prognosis. METHODS: We retrospectively analyzed the medical records of patients with a germinal BRCA1/2 pathologic variant who had undergone risk-reducing salpingo-oophorectomy at Asan Medical Center (Seoul, Korea) between January 2013 and December 2020. All pathologic reports were made based on the sectioning and extensively examining the fimbriated end of the fallopian tube (SEE/FIM) protocol. RESULTS: Out of 243 patients who underwent risk-reducing salpingo-oophorectomy, 121 (49.8%) had a BRCA1 mutation, 119 (48.9%) had a BRCA2 mutation, and three (1.2%) had both mutations. During the procedure, four (3.3%) patients with a BRCA1 mutation were diagnosed with serous tubal intraepithelial carcinoma (STIC) or serous tubal intraepithelial lesion (STIL), and another four patients (3.3%) were diagnosed with occult cancer despite no evidence of malignancy on preoperative ultrasound. In the BRCA2 mutation group, we found one (0.8%) case of STIC, but no cases of STIL or occult cancer. During the median follow-up period of 98 months (range, 44-104) for STIC and 54 months (range, 52-56) for STIL, none of the patients diagnosed with these precursor lesions developed primary peritoneal carcinomatosis. CONCLUSIONS: Risk-reducing salpingo-oophorectomy, in asymptomatic Korean patients with BRCA1/2 pathogenic variants, detected ovarian cancer and precursor lesions, including STIC or STIL. Furthermore, our follow-up period did not reveal any instances of primary peritoneal carcinomatosis, suggesting a limited body of evidence supporting the imperative need for adjuvant treatment in patients diagnosed with these precursor lesions during risk-reducing salpingo-oophorectomy.

Fortuitously detected primary ovarian carcinoid tumor: A case report.

RATIONALE: Carcinoid tumors, derived from the cells of the disseminated neuroendocrine system, are rare, slow-growing neuroendocrine neoplasms that display a relatively indolent disease course. The majority of carcinoids are found within the gastrointestinal tract and bronchopulmonary system. Primary ovarian carcinoids are rare and account for merely 1% of all carcinoid tumors. We describe our experience of a rare case of primary ovarian carcinoid, presenting as chronic constipation, with no other carcinoid symptoms such as flushing, diarrhea, and wheezing. PATIENT CONCERNS: A 51-year-old postmenopausal woman with chronic constipation visited the clinic for routine check-up of her preexisting uterine fibroids. She had undergone hemorrhoidectomy 3 years ago. Physical examination revealed a soft abdomen without direct or rebound tenderness. Transvaginal ultrasonography revealed two subserosal fibroids, which had increased in size compared with previous ultrasonographic findings. A 3 cm hyperechoic mass was also detected in the right ovary. Her blood and urine tests were unremarkable, with no ascites in the pelvic cavity. She had a normal CA-125 level of 5.5 units/mL. DIAGNOSIS, INTERVENTIONS, AND OUTCOMES: The patient underwent a robot-assisted hysterectomy and right salpingo-oophorectomy because of enlarging fibroids and the right ovarian mass. Subsequently, based on the pathological and immunohistochemical findings, she was diagnosed with a primary ovarian carcinoid. The mass consisted of the insular and trabecular types of tumor cells. It was positive for pan-cytokeratin and synaptophysin, and the Ki-67 proliferation index was less than 1%. A follow-up positron emission tomography-computed tomography revealed no distant metastasis. Six months postoperatively, the patient was doing well without any signs of recurrence. LESSONS: Primary ovarian carcinoids without teratoma components are rare. It is crucial to make an accurate diagnosis based on the immunohistochemical staining results. Diagnosis in the early stages of the disease are associated with a favorable prognosis, but regular follow-up is mandatory.

The uterine adenosarcoma with postoperative residual in a woman treated by total abdominal hysterectomy/bilateral salpingo-oophorectomy: A case report and review of literature.

BACKGROUND: In patients with uterine adenosarcoma, a total abdominal hysterectomy (TAH) with bilateral salpingo-oophorectomy (BSO) is typically recommended as an initial treatment. There is no consensus on adjuvant therapies. CASE: We report the case of a patient with uterine adenosarcoma with postoperative residual disease. We performed four courses of adjuvant chemotherapy, including Ifosfamide, Mesna, and Adriamycin, and whole pelvic radiation with a dose of 50.4 Gy/28 Fr. CONCLUSION: A combination of chemotherapy and radiotherapy may be a promising treatment option for uterine adenosarcoma with postoperative residual disease.

Clinical significance of risk-reducing salpingo-oophorectomy in patients with BRCA1/2 mutation.

OBJECTIVE: Serous tubal intraepithelial carcinoma (STIC) is a precursor lesion which is located in the distal fallopian tube and causes high grade serous ovarian carcinoma (HGSOC). The incidence of STIC for women underwent risk reducing salpingo-oophorectomy for BRCA mutation varies from 0.6 to 7% and its clinical outcomes are still unclear. The aim of this study was to demonstrate the incidence of STIC and HGSOC in BRCA1/2 mutation carriers after risk reducing salpingo-oophorectomy (RRSO) and the clinical outcomes of these patients. MATERIAL AND METHODS: We retrospectively reviewed the records of 48 BRCA1 and/or 2 mutation carriers who underwent prophylactic salpingo-oophorectomy with or without hysterectomy at the Department of Obstetrics and Gynecology, Bursa Uludag University between January 2000 and January 2022. INCLUSION CRITERIA: BRCA 1 and/or 2 mutation carriers diagnosed by genetic testing, asymptomatic patients with no abnormal findings on pelvic examination. EXCLUSION CRITERIA: patients with no abnormal findings on pelvic examination and a presence of a personal history of ovarian, fallopian tube or peritoneal cancer. RESULTS: A total of 48 BRCA 1 and/or 2 mutation carriers underwent RRSO. STIC was diagnosed in 1 (2,0%) patient and restaging surgery was not performed. Primary peritoneal carcinoma (PPC) did not develop during the 20 months follow-up period. One (2.0%) patient was diagnosed with occult ovarian cancer. Restaging surgery was performed and chemotherapy treatments were given after surgery. A pelvic recurrence developed 25 months after the occult cancer diagnosis in the follow up period. One (2.0%) patient with normal histopathological findings after RRSO was diagnosed with peritoneal cancer 57 months after the operation. CONCLUSION: The risk of PPC continues after RRSO. Therefore, close follow-up procedure is very important for early diagnosis and effective treatment of patients with PPC after RRSO.