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)

Risk-Reducing Salpingo-Oophorectomy and the Use of Hormone Replacement Therapy Below the Age of Natural Menopause: Scientific Impact Paper No. 66 October 2021: Scientific Impact Paper No. 66.

This paper deals with the use of hormone replacement therapy (HRT) after the removal of fallopian tubes and ovaries to prevent ovarian cancer in premenopausal high risk women. Some women have an alteration in their genetic code, which makes them more likely to develop ovarian cancer. Two well-known genes which can carry an alteration are the BRCA1 and BRCA2 genes. Examples of other genes associated with an increased risk of ovarian cancer include RAD51C, RAD51D, BRIP1, PALB2 and Lynch syndrome genes. Women with a strong family history of ovarian cancer and/or breast cancer, may also be at increased risk of developing ovarian cancer. Women at increased risk can choose to have an operation to remove the fallopian tubes and ovaries, which is the most effective way to prevent ovarian cancer. This is done after a woman has completed her family. However, removal of ovaries causes early menopause and leads to hot flushes, sweats, mood changes and bone thinning. It can also cause memory problems and increases the risk of heart disease. It may reduce libido or impair sexual function. Guidance on how to care for women following preventative surgery who are experiencing early menopause is needed. HRT is usually advisable for women up to 51 years of age (average age of menopause for women in the UK) who are undergoing early menopause and have not had breast cancer, to minimise the health risks linked to early menopause. For women with a womb, HRT should include estrogen coupled with progestogen to protect against thickening of the lining of the womb (called endometrial hyperplasia). For women without a womb, only estrogen is given. Research suggests that, unlike in older women, HRT for women in early menopause does not increase breast cancer risk, including in those who are BRCA1 and BRCA2 carriers and have preventative surgery. For women with a history of receptor-negative breast cancer, the gynaecologist will liaise with an oncology doctor on a case-by-case basis to help to decide if HRT is safe to use. Women with a history of estrogen receptor-positive breast cancer are not normally offered HRT. A range of other therapies can be used if a woman is unable to take HRT. These include behavioural therapy and non-hormonal medicines. However, these are less effective than HRT. Regular exercise, healthy lifestyle and avoiding symptom triggers are also advised. Whether to undergo surgery to reduce risk or not and its timing can be a complex decision-making process. Women need to be carefully counselled on the pros and cons of both preventative surgery and HRT use so they can make informed decisions and choices.

Vaginal NOTES approach for risk-reducing salpingo-oophorectomy in BRCA mutation carriers: A video demonstration.

Risk-reducing bilateral salpingo-oophorectomy (BSO) is an important option to prevent the development of ovarian and fallopian tube cancers in women with a BRCA1/2 mutation. Conventional laparoscopy is the current preferred technique since it is associated with less morbidity compared to laparotomy. Transvaginal Natural Orifice Transluminal Endoscopic Surgery (vNOTES) is a new minimally invasive technique that allows access to the peritoneal cavity through the vagina without skin incisions. The vNOTES technique for risk-reducing BSO is presented herein. This article includes a narrated, step-by-step video demonstration of the entire procedure. Risk-reducing BSO using the vNOTES approach is a feasible technique that appears to be simple, safe, and reproducible. This technique has the potential to improve patients' surgical experience and provide good long-term functional and cosmetics outcomes. This technique needs to be further evaluated and compared to the conventional laparoscopic approach.

Efficacy of risk-reducing salpingo-oophorectomy in BRCA1-2 variants and clinical outcomes of follow-up in patients with isolated serous tubal intraepithelial carcinoma (STIC).

OBJECTIVE: Serous tubal intraepithelial carcinoma (STIC) is currently considered the precursor lesion of pelvic high-grade serous carcinoma. The management of STIC diagnosed after risk-reducing salpingo-oophorectomy (RRSO) in women with BRCA1-2 variants remains unclear. The aim of our study was to evaluate the incidence of STIC, serous tubal intraepithelial lesions (STIL) and occult invasive cancer (OC) and to determine the long-term outcomes of these patients. METHODS: We conducted a retrospective study of patients with BRCA 1-2 variants who underwent RRSO between January-2010 and Dicember-2020 at the Clinic of Gynaecology of University of Padova. INCLUSION CRITERIA: women with a negative pelvic examination at the last screening prior to RRSO, patients with fallopian tubes analysed using the SEE-FIM protocol. EXCLUSION CRITERIA: patients with a positive gynaecologic screening or with ovarian/tubal cancer prior to RRSO. RESULTS: We included 153 patients. STICs were diagnosed in 4 patients (2.6%) and STILs in 6 patients (3.9%). None of the patients with STIC underwent restaging surgery or adjuvant chemotherapy; all patients were followed closely every 6 months. None of the patients developed primary peritoneal carcinomas (PPCs) with a median FUP of 54.5 months (15-106). OC was diagnosed in 3 patients (2%). All patients with OC underwent staging surgery, and one patient developed a peritoneal carcinoma (PC) after 18 months by staging surgery. CONCLUSION(S): The incidence of STIC, STIL and OC after RRSO in BRCA1-2 variants was low. Our results demonstrated that long-term close surveillance in patients diagnosed with STIC should be considered a possible management strategy.

Evaluation of a patient decision aid for BRCA1/2 pathogenic variant carriers choosing an ovarian cancer prevention strategy.

OBJECTIVE: Risk-reducing surgery is advised to BRCA1/2 pathogenic variant (PV) carriers around the age of 40 years to reduce ovarian cancer risk. In the TUBA-study, a multicenter preference study (NCT02321228), BRCA1/2-PV carriers are offered a choice: the standard strategy of risk-reducing salpingo-oophorectomy or the novel strategy of risk-reducing salpingectomy with delayed oophorectomy. We evaluated feasibility and effectiveness of a patient decision aid for this choice. METHODS: Premenopausal BRCA1/2-PV carriers were counselled for risk-reducing surgical options in the TUBA-study; the first cohort was counselled without and the second cohort with decision aid. Evaluation was performed using digital questionnaires for participating women and their healthcare professionals. Outcome measures included actual choice, feasibility (usage and experiences) and effectiveness (knowledge, cancer worry, decisional conflict, decisional regret and self-estimated influence on decision). RESULTS: 283 women were counselled without and 282 women with decision aid. The novel strategy was chosen less frequently in women without compared with women with decision aid (67% vs 78%, p = 0.004). The decision aid was graded with an 8 out of 10 by both women and professionals, and 78% of the women would recommend this decision aid to others. Users of the decision aid reported increased knowledge about the options and increased insight in personal values. Knowledge on cancer risk, decisional conflict, decisional regret and cancer worry were similar in both cohorts. CONCLUSIONS: The use of the patient decision aid for risk-reducing surgery is feasible, effective and highly appreciated among BRCA1/2-PV carriers facing the decision between salpingo-oophorectomy or salpingectomy with delayed oophorectomy.

Risk of cardiovascular disease among women carrying BRCA mutations after risk-reducing bilateral salpingo-oophorectomy: A population-based study.

OBJECTIVE: Examine the risk of cardiovascular disease (CVD) following risk reducing bilateral salpingo-oophorectomy (RRBSO) among women with BRCA mutations. METHODS: In this retrospective population-based study in British Columbia, Canada, between 1996 and 2017, we compared the risk of CVD among women with known BRCA mutations who underwent RRBSO before the age of 50 (n = 360) with two groups of age-matched women without known BRCA mutations: 1) women who underwent bilateral oophorectomy (BO) for benign conditions (n = 3600); and, 2) women with intact ovaries who had hysterectomy or salpingectomy (n = 3600). Our primary outcome was CVD (a composite (any of) myocardial infarction, heart failure, and/or cerebrovascular disease). Secondary outcomes included a diagnostic code for predisposing conditions (hypertension, dyslipidemia, and/or diabetes mellitus), and use of cardioprotective medications (statins and/or beta-blockers). RESULTS: We report no significant increased risk for CVD between women with BRCA mutations and women who underwent BO (aHR = 1.08, 95%CI: 0.72-1.62), but women with BRCA mutations were less likely to be diagnosed with predisposing conditions (aHR = 0.69, 95%CI: 0.55-0.85). Compared to women without BRCA mutations with intact ovaries who underwent hysterectomy or salpingectomy, women with BRCA mutations had significantly increased risk for CVD (aHR = 1.82, 95%CI: 1.18-2.79) and were less likely to be diagnosed with predisposing conditions (aHR = 0.78, 95%CI: 0.62-0.97) and to fill cardioprotective medications (aHR = 0.88, 95%CI: 0.64-1.22). CONCLUSION: Our results suggest an opportunity for improved prevention of CVD in women with BRCA mutations after prophylactic oophorectomy. Despite the observed lower prevalence of predisposing conditions for CVD and lesser use of cardioprotective medications, this population did not have a lower rate of CVD.

Large ovarian tumors in adolescents, a systematic review of reported cases, diagnostic findings and surgical management.

The purpose of this study was to analyze the published cases regarding large ovarian masses in adolescents, in order to find useful clinical implications for the diagnosis and management of the condition. The methodology employed a systematic review of reported cases of large/giant ovarian tumor in adolescence. The main objective was to assess the imagery findings, histology of the tumor, and the type of surgery performed. Our study included 58 patients with the tumor diameters ranged between 11 and 42 cm, with a median value of 22.75 cm and a mean diameter of 24.66 ± 8.50 cm. The lesions were benign in 47 cases (81%), borderline in 2 cases (3.4%), and malign in 9 cases (15.6%). We found no statistically significant difference (p > 0.05) between the size of the tumors and the ovarian markers levels. At the same time, a statistically significant difference was identified (p=<0,001) between elevated levels of the serum markers and the malignant tumor type (OR = 12.45; CI95 = 2.55-94.77). The main types of surgery performed were cystectomy (35 cases), oophorectomy (4 cases), salpingo-oophorectomy (18 cases). Open laparotomy was performed in 46 cases on tumors with a median diameter of 25 ± 8.8 cm, while laparoscopy was done in 12 cases on tumors with a median diameter of 23.7 ± 7.6 cm. For optimal surgical management, it is advisable to assess first the imagery findings and tumor markers. Then, the laparoscopic approach should be considered as a feasible option, especially in cases where there are no predictive factors for a malign disease.

Uptake and timing of risk-reducing salpingo-oophorectomy among patients with BRCA1 and BRCA2 mutations.

BACKGROUND: In women with BRCA mutations, risk-reducing bilateral salpingo-oophorectomy has been shown to decrease gynecologic cancer-specific and overall mortality. The National Comprehensive Cancer Network recommends that patients with BRCA mutations undergo risk-reducing bilateral salpingo-oophorectomy between the ages of 35 and 40 years for BRCA1 mutation carriers and between the ages of 40 and 45 years for BRCA2 mutation carriers or after childbearing is complete. Currently, uptake and timing of risk-reducing bilateral salpingo-oophorectomy and reasons for delays in risk-reducing bilateral salpingo-oophorectomy are not well understood. OBJECTIVE: We sought to evaluate uptake and timing of risk-reducing bilateral salpingo-oophorectomy among women with BRCA1 and BRCA2 mutations concerning the National Comprehensive Cancer Network guidelines and reasons for delays in risk-reducing bilateral salpingo-oophorectomy. STUDY DESIGN: In this retrospective chart review, we identified women with BRCA1 and BRCA2 mutations who discussed risk-reducing bilateral salpingo-oophorectomy with a provider between 2012 and 2021. Uptake of risk-reducing bilateral salpingo-oophorectomy was documented, and patients were classified as having timely or delay in risk-reducing bilateral salpingo-oophorectomy based on the National Comprehensive Cancer Network guidelines. For those with delay in risk-reducing bilateral salpingo-oophorectomy, reasons cited for delay were collected. Comparative statistical analyses were performed to evaluate characteristics of those with timely vs delayed risk-reducing bilateral salpingo-oophorectomy. A multivariable logistic regression model was used to evaluate the associations among factors related to timing of risk-reducing bilateral salpingo-oophorectomy. RESULTS: We identified 638 BRCA1 and BRCA2 mutation carriers seen between 2012 and 2021. Of these patients, 306 (48.0%) had undergone risk-reducing bilateral salpingo-oophorectomy and 332 (52.0%) had not. When evaluating the timing of risk-reducing bilateral salpingo-oophorectomy, 136 (21.3%) underwent timely risk-reducing bilateral salpingo-oophorectomy, 239 (37.5%) had delays in risk-reducing bilateral salpingo-oophorectomy, and 263 (41.2%) had not undergone risk-reducing bilateral salpingo-oophorectomy but were younger than the National Comprehensive Cancer Network age guidelines; therefore, they were neither timely nor delayed. Patients with delay in risk-reducing bilateral salpingo-oophorectomy were significantly older at the time of genetic testing than those with timely risk-reducing bilateral salpingo-oophorectomy (mean, 49.8 vs 36.3 years; P<.001). Of the 306 patients who underwent risk-reducing bilateral salpingo-oophorectomy, those with delayed risk-reducing bilateral salpingo-oophorectomy had a significantly shorter interval between BRCA identification and risk-reducing bilateral salpingo-oophorectomy than those with timely risk-reducing bilateral salpingo-oophorectomy (median, 8.7 vs 17.6 months; P<.001). Patients with delay in risk-reducing bilateral salpingo-oophorectomy were more likely to have a personal history of cancer than those with timely risk-reducing bilateral salpingo-oophorectomy (49.8% vs 37.5%; P=.028). Of the 239 women with delay in risk-reducing bilateral salpingo-oophorectomy, 188 (78.7%) had delayed BRCA mutation identification, 29 (12.1%) had menopausal concerns, 17 (7.1%) had ongoing cancer treatment, 12 (5.0%) had coordination with breast surgery, 20 (8.4%) had miscellaneous reasons, and 19 (7.9%) had no reason documented. In the multivariate model, older age at BRCA diagnosis (odds ratio, 0.73; 95% confidence interval, 0.68-0.78; P<.001) was significantly associated with delayed risk-reducing bilateral salpingo-oophorectomy timing; those with BRCA2 mutation type were 7.54 times as likely to have timely risk-reducing bilateral salpingo-oophorectomy than BRCA1 mutation carriers (odds ratio, 7.54; 95% confidence, 3.70-16.42; P<.001). CONCLUSION: Nearly 38% of BRCA1 and BRCA2 mutation carriers undergo or have yet to undergo risk-reducing bilateral salpingo-oophorectomy over the recommended National Comprehensive Cancer Network age. The most common reason for the delay in risk-reducing bilateral salpingo-oophorectomy was delayed identification of BRCA mutation, noted in 79% of patients with delayed risk-reducing bilateral salpingo-oophorectomy. Timely genetic testing for eligible patients can increase appropriately timed risk-reducing bilateral salpingo-oophorectomy for the prevention of ovarian cancer and reduction of mortality in BRCA mutation carriers.

What Happens After Menopause? (WHAM): A prospective controlled study of cardiovascular and metabolic risk 12 months after premenopausal risk-reducing bilateral salpingo-oophorectomy.

OBJECTIVE: To prospectively measure cardiometabolic risk 12 months after premenopausal risk-reducing bilateral salpingo-oophorectomy (RRBSO) compared to a similar age comparison group, and the effects of Hormone Therapy (HT) on cardiometabolic risk. METHODS: Prospective observational study of 95 premenopausal women planning RRBSO and 99 comparisons who retained their ovaries. At baseline and 12 months, blood pressure (BP), Body Mass Index (BMI), waist and hip circumference, fasting total, HDL and LDL cholesterol, triglycerides, high-sensitivity C-reactive protein, glucose and insulin were measured and HOMA-IR was calculated. Chi-square tests, t-tests and adjusted logistic regression models were used to compare groups. RESULTS: Baseline cardiometabolic phenotypes were similar between groups but more RRBSO participants were overweight/obese with higher waist/hip ratios. By 12 months, BP and cardiometabolic phenotypes were largely unchanged. Paired t-tests showed statistically significant increases in BMI (p = 0.037) and weight (p = 0.042) and larger increases in waist circumference (p < 0.001) and waist-hip ratio (p = 0.009) after RRBSO vs comparisons. However, these were not significant when adjusted for baseline values. After RRBSO 60% initiated Hormone Therapy (HT). Paired t-tests demonstrated that non-HT users had a significantly greater mean increase in waist circumference of 4.3 cm (95% CI 2.0-6.5) compared to 1.3 cm in HT users (95% CI -0.2-2.7, p < 0.001), which remained significant when adjusted for baseline values (p = 0.02). At 12 months, mean waist circumference was 2.94 cm greater in non-HT users compared to HT users. CONCLUSIONS: Cardiometabolic risk markers are largely unchanged 12 months after RRBSO. Hormone Therapy after RRBSO may prevent against an increase in waist circumference.

Trends and timing of risk-reducing mastectomy uptake in unaffected BRCA1 and BRCA2 carriers in Slovenia.

OBJECTIVES: Risk-reducing mastectomy (RRM) is one of key prevention strategies in female carriers of germline BRCA pathogenic/likely pathogenic variants (PV/LPV). We retrospectively investigated the rate, timing and longitudinal trends of bilateral RRM uptake and the incidence and types of cancers among unaffected BRCA carriers who underwent genetic counseling at the Institute of Oncology Ljubljana in Slovenia. MATERIALS AND METHODS: Female BRCA carriers without personal history of cancer were included in the study. Clinical data on PV/LPV type, date of RRM, type of reconstructive procedure, occult carcinoma and histopathology results was collected and analyzed. RESULTS: Of the 346 unaffected BRCA carriers (median age 43 years, 70% BRCA1, 30% BRCA2, median follow-up 46 months) who underwent genetic testing between October 1999 and December 2019, 25.1% had a RRM (range 35-50 years, median age at surgery 38 years). A significant difference in time to prophylactic surgery between women undergoing RRM only vs. women undergoing RRM combined with risk-reducing salpingo-oophorectomy was observed (22.6 vs 8.7 months, p = 0.0009). We observed an upward trend in the annual uptake in line with the previously observed Angelina Jolie effect. In 5.7% of cases, occult breast cancer was detected. No women developed breast cancer after RRM. Women who did not opt for surgical prevention developed BRCA1/2-related cancers (9.3%). CONCLUSION: The uptake of RRM among unaffected BRCA carriers is 25.1% and is similar to our neighboring countries. No women developed breast cancer after RRM while women who did not opt for surgical prevention developed BRCA1/2 related cancers in 9.3% of cases. The reported data may provide meaningful aid for carriers when deciding on an optimal prevention strategy.

Inflammation calls for more: Severe pelvic inflammatory disease with or without endometriosis. Outcomes on 311 laparoscopically treated women.

OBJECTIVE: To study possible associations between endometriosis and pelvic inflammatory disease (PID). DESIGN: Retrospective cohort analysis over 14 consecutive years, based on medical records and insurance coding in a tertiary care endometriosis reference center. SETTING: Tertiary care reference center for endometriosis. PATIENTS: Retrospective analysis on all women submitted to laparoscopy in our Unit MAIN OUTCOME MEASURES: Intra-operative data about complications and fertility-impairing procedures, intra-, peri- and post-operative complications. INTERVENTIONS: Retrospective disease codes-triggered chart analysis. RESULTS: The study population was divided into two groups: Group 1 included women with PID and no endometriosis (n = 115); Group 2 included women with PID and endometriosis (n = 96). Endometriosis had a prevalence of 63 % in patients submitted to surgery for PID, significantly higher than the one reported in general population and than the one reported in a Tertiary Care Endometriosis Unit. A significantly higher number of salpingectiomes was needed in group 2 patients (208 versus 80, p < 0.0001). CONCLUSIONS: This study seems to confirm an higher prevalence of pelvic inflammatory disease in endometriosis patients. Intra-operative findings of PID with associated endometriosis show more aggressive patterns.

Short- and long-term outcomes for single-port risk-reducing salpingo-oophorectomy with and without hysterectomy for women at risk for gynecologic cancer.

INTRODUCTION: Risk-reducing salpingo-oophorectomy has been established as one of the most effective strategies in risk reduction for ovarian and breast cancers among women at increased genetic risk. However, there are limited data regarding the single-port laparoscopic platform in the field of risk-reducing surgery. Our objective was to describe outcomes after single-port risk-reducing salpingo-oophorectomy with or without hysterectomy for reduction of ovarian, breast, or endometrial cancer risk. METHODS: A retrospective, single institution (Canadian Task Force Classification II.2) analysis was performed in women at high genetic or familial risk for ovarian/tubal/primary peritoneal cancer or with personal history of breast cancer who underwent single-port laparoscopic risk-reducing salpingo-oophorectomy with or without hysterectomy between October 2009 and December 2015. Data were collected on patient demographics, surgical procedure and characteristics, intra-operative findings, and post-operative outcomes. RESULTS: In total, 187 single-port laparoscopic surgeries were performed with a median follow-up of 204 (IQR 25-749) days. BRCA1/2, Lynch syndrome, or Cowden syndrome was diagnosed in 64.0% of patients. Additionally, 32.1% had a personal history of breast cancer, and 3.2% reported strong family history of ovarian and/or breast cancer. Single-port risk-reducing salpingo-oophorectomy with hysterectomy was performed in 53.5% of patients. The rate of adverse outcomes, including conversion to multiport laparoscopy or laparotomy (1.6%), intra-operative injury (1.6%), deep vein thrombosis (0.5%), urinary tract infection (2.7%), and/or incisional cellulitis (4.3%) were low. Three patients (1.6%) were diagnosed with malignancy on final pathology. All three patients were BRCA1-positive and their CA125 values were significantly lower than those without malignancy (p=<0.0001). CONCLUSIONS: Single-port laparoscopy is a safe option for patients undergoing risk-reducing salpingo-oophorectomy with or without hysterectomy. Standardized pre-operative evaluation criteria are needed to determine absolute risk of incidental malignancy, and the risk of identifying a malignancy should be reiterated to patients during pre-operative counseling.

Surgical ovarian suppression for adjuvant treatment in hormone receptor positive breast cancer in premenopausal patients.

OBJECTIVE: Ovarian suppression is recommended to complement endocrine therapy in premenopausal women with breast cancer and high-risk features. It can be achieved by either medical ovarian suppression or therapeutic bilateral salpingo-oophorectomy. Our objective was to evaluate characteristics of patients with stage I-III hormone receptor positive primary breast cancer who underwent bilateral salpingo-oophorectomy at our institution. MATERIALS AND METHODS: Premenopausal women with stage I-III hormone receptor positive primary breast cancer diagnosed between January 2010 and December 2014 were identified from a database. Patients with confirmed BRCA1/2 mutations were excluded. Distribution of characteristics between treatment groups was assessed using χ2 test and univariate logistic regression. A multivariate model was based on factors significant on univariate analysis. RESULTS: Of 2740 women identified, 2018 (74%) received endocrine treatment without ovarian ablation, 516 (19%) received endocrine treatment plus ovarian ablation, and 206 (7.5%) did not receive endocrine treatment. Among patients undergoing ovarian ablation 282/516 (55%) received medical ovarian suppression, while 234 (45%) underwent bilateral salpingo-oophorectomy. By univariate logistic analyses, predictors for ovarian ablation were younger age (OR 0.97), histology (other vs ductal: OR 0.23), lymph node involvement (OR 1.89), higher International Federation of Gynecology and Obstetrics (FIGO) stage (stage II vs I: OR 1.48; stage III vs I: OR 2.86), higher grade (grade 3 vs 1: OR 3.41; grade 2 vs 1: OR 2.99), chemotherapy (OR 1.52), and more recent year of diagnosis (2014 vs 2010; OR 1.713). Only year of diagnosis, stage, and human epidermal growth factor receptor 2 (HER-2) treatment remained significant in the multivariate model. Within the cohort undergoing ovarian ablation, older age (OR 1.05) was associated with therapeutic bilateral salpingo-oophorectomy. Of 234 undergoing bilateral salpingo-oophorectomy, 12 (5%) mild to moderate adverse surgical events were recorded. CONCLUSIONS: Bilateral salpingo-oophorectomy is used frequently as an endocrine ablation strategy. Older age was associated with bilateral salpingo-oophorectomy. Perioperative morbidity was acceptable. Evaluation of long-term effects and quality of life associated with endocrine ablation will help guide patient/provider decision-making.

Effect of surgical approach on risk of recurrence after vaginal brachytherapy in early-stage high-intermediate risk endometrial cancer.

OBJECTIVE: The objective was to determine if surgical approach affects time to recurrence in early-stage high-intermediate risk endometrial cancer (HIR-EC) treated with adjuvant vaginal brachytherapy (VBT). METHODS: In this retrospective cohort study, HIR-EC patients treated with VBT between 2005 and 2017 were identified and those who received open or minimally invasive hysterectomies (MIS) were included. Clinical and surgical variables were analyzed and time to recurrence was compared between surgical groups. RESULTS: We identified 494 patients, of which 363 had MIS hysterectomies, 92.5% had endometrioid histology, 45.7% were stage IA and 48.0% stage IB. Open hysterectomy patients had higher BMIs (p = 0.007), lower rates of lymph node sampling (p < 0.001) and lymphovascular space invasion (LVSI) (p = 0.036), however in patients who recurred, no differences were noted between groups. Overall, 65 patients (13.2%) recurred, 14 in the open group (10.7%) and 51 in the MIS group (14.0%) (p = 0.58), while vaginal recurrences were noted in 4.6% and 6.1% respectively. When compared to the open group, the MIS group had a significantly shorter time to any recurrence (p = 0.022), to pelvic (p = 0.05) and locoregional recurrence (p = 0.021) and to death from any cause (p = 0.039). After adjusting for age, BMI, grade, LVSI and surgery date, the MIS group had a higher risk of any recurrence (HR 2.29 (1.07-4.92), p = 0.034) and locoregional recurrence (HR 4.18 (1.44-12.1), p = 0.008). CONCLUSIONS: Patients with HIR-EC treated with VBT after MIS hysterectomy have a shorter time to recurrence and higher risk of recurrence when compared to open hysterectomy patients. Further studies into the safety of MIS in high-intermediate risk patients are required.

Practice variation in bilateral salpingo-oophorectomy at benign abdominal hysterectomy: a population-based study.

BACKGROUND: Bilateral salpingo-oophorectomy at benign hysterectomy is not recommended in premenopausal women who are in the premenopausal stage because of its potential associations with increased all-cause mortality and cardiovascular disease; however, contemporary practice patterns are unknown. OBJECTIVE: This study aimed to quantify between-surgeon variation in bilateral salpingo-oophorectomy and identify surgeon and patient characteristics associated with bilateral salpingo-oophorectomy to evaluate current quality of care and identify targets for knowledge translation and future research. STUDY DESIGN: We conducted a population-based retrospective cross-sectional study of adult women (≥20 years) undergoing benign abdominal hysterectomy from 2014 to 2018 in Ontario, Canada. Hierarchical multivariable logistic regression models, stratified by age group (<45, 45-54, ≥55 years), were used to model between-surgeon variation after multivariable adjustment for patient and surgeon characteristics. Cases of bilateral salpingo-oophorectomy were classified as potentially appropriate or potentially avoidable based on the presence or absence of diagnostic indications. RESULTS: Of 44,549 eligible women, 17,797 (39.9%) underwent concurrent bilateral salpingo-oophorectomy, and 26,752 (60.1%) did not. In all three age strata, the individual surgeon providing care was one of the strongest factors influencing whether patients received bilateral salpingo-oophorectomy (median odds ratio, 2.00-2.53). Surgeons accounted for more than 22% of the residual observed variation in bilateral salpingo-oophorectomy in women aged 45-54 years compared with 16% and 14% of the residual observed variation in bilateral salpingo-oophorectomy in women aged <45 and ≥55 years, respectively. Non-gynecologic patient factors, such as obesity (odds ratio, 1.33; 95% confidence interval, 1.17-1.52; P<.001) and residing in low-income regions (odds ratio, 1.34; 95% confidence interval, 1.16-1.55; P<.001), were also associated with bilateral salpingo-oophorectomy. Approximately 40% of patients who underwent bilateral salpingo-oophorectomy had no indication for the procedure in their discharge records. CONCLUSION: Marked between-surgeon variation in bilateral salpingo-oophorectomy rates, even after adjusting for patient case mix, suggests ongoing uncertainty in practice. Stronger evidence-based guidelines on the risks and benefits of salpingo-oophorectomy as women age are needed, particularly focusing on perimenopausal women.

Concomitant Bilateral Salpingo-Oophorectomy at Hysterectomy: Differences by Race and Menopausal Status in the Veterans Affairs Health Care System, 2007-2014.

Background: Hysterectomy can be performed with concomitant bilateral salpingo-oophorectomy (BSO) to treat symptomatic pathology of the ovary (e.g., endometriosis) or to prevent ovarian cancer. Our objective was to examine the relationship between race and concomitant BSO by menopausal status in the Veterans Affairs (VA) health care system. Methods: This is a longitudinal study utilizing VA administrative data to identify hysterectomies provided or paid for by VA (i.e., source of care) between 2007 and 2014. We defined BSO as removal of both ovaries and fallopian tubes at the time of hysterectomy, identified by International Classification of Diseases-Ninth Revision codes. Covariates included demographic (e.g., ethnicity) and gynecological diagnoses (e.g., endometriosis). We used generalized linear models with a log-link and binomial distribution to estimate associations of race with BSO by menopausal status and source of care. Results: We identified 6,785 Veterans with hysterectomies, including 2,320 with concomitant BSO. Overall, Black Veterans were more likely to be single, obese, and undergo abdominal hysterectomy. After adjustment, premenopausal Black Veterans had a 41% lower odds of BSO than their White counterparts (odds ratio [OR]: 0.59, 95% confidence interval [CI]: 0.51-0.68). Stratifying on source of care, these results remained unchanged (provided: OR: 0.61, 95% CI: 0.52-0.72; paid: OR: 0.58, 95% CI: 0.48-0.71). There was insufficient evidence of an association among postmenopausal Veterans. Conclusions: Premenopausal Black Veterans are less likely to undergo BSO even after adjustment for salient characteristics. Our findings may have implications for equitable gynecological care for Veterans. Additional research is needed to better understand the role of differential preferences or cancer risk in these racial differences.

Management of high, moderate, and low penetrance ovarian cancer susceptibility mutations: an assessment of current risk reduction practices.

OBJECTIVE: Limited information exists regarding risk reduction strategies for women with moderate and low penetrance ovarian cancer susceptibility mutations. We sought to assess current risk reduction practice patterns for carriers of these mutations through a survey of members of the Society of Gynecologic Oncology. METHODS: Society of Gynecologic Oncology members were emailed a survey consisting of two vignettes: (1) a 35-year-old premenopausal woman; (2) a 55-year-old postmenopausal woman with comorbidities. Each vignette contained sub-scenarios in which the patient had either a BRCA1 (relative risk (RR)=30-60), RAD51C (RR=5.0), or ATM (RR=1.5-2.0) mutation. Respondents were queried about their preferred management approach. Summary statistics were performed to describe results of the survey. We used χ2 testing for statistical analyses, comparing results according to mutation type and demographic information. RESULTS: A total of 193 (15%) of 1284 Society of Gynecologic Oncology members responded. For the premenopausal woman, 99%, 80%, and 40% would perform a risk reducing salpingo-oophorectomy prior to menopause in the setting of a BRCA1, RAD51C, and ATM mutation, respectively. For the postmenopausal woman, 98%, 85%, and 42% would proceed with risk reducing salpingo-oophorectomy in the setting of a BRCA1, RAD51C, and ATM mutation, respectively. Response distribution for carriers of RAD51C and ATM mutations were different from BRCA1 in both vignettes (p<0.001). CONCLUSIONS: Respondents were more likely to perform risk reducing salpingo-oophorectomy, in the setting of a BRCA1, RAD51C, and ATM mutation, earlier and more frequently in the setting of a BRCA1 mutation. However, there was a lack of consensus about management of the moderate and low penetrance mutations, suggesting that more data regarding age specific risks and appropriate risk reduction strategies for these alterations are needed.

Incidence of lymphedema in the lower limbs and lymphocyst formation within one year of surgery for endometrial cancer: A prospective longitudinal multicenter study.

OBJECTIVE: The study aimed to determine the incidence of lower limb lymphedema (LLL) after surgery for endometrial cancer (EC) by means of three methods, and to determine the incidence of lymphocysts after one year. METHODS: A prospective longitudinal multicenter study was conducted in 14 hospitals in Sweden. Two-hundred-and-thirty-five women with EC were included; 116 underwent surgery that included lymphadenectomy (+LA) and 119 were without lymphadenectomy (-LA). Lymphedema was assessed objectively on four occasions; preoperatively, at 4-6 weeks, six months and one year postoperatively using systematic measurement of leg circumferences, enabling calculation of leg volumes, and a clinical grading of LLL, and subjectively by the patient's perception of lymphedema measured by a lymphedema-specific quality-of-life instrument. Lymphocyst was evaluated by vaginal ultrasonography. RESULTS: After one year the incidence of LLL after increase in leg volume adjusted for body mass index was 15.8% in +LA women and 3.4% in -LA women. The corresponding figures for clinical grading were 24.1% and 11.8%, and for patient-reported perceived LLL 10.7% and 5.1%. The agreement between the modalities revealed fair to moderate correlation between patient-reported LLL and clinical grading, but poor agreement between volume increase and patient-reported LLL or clinical grading. Lymphocysts were found in 4.3% after one year. CONCLUSIONS: Although the incidence of LLL and lymphocysts after surgery for EC including LA seemed to be relatively high the study demonstrated significant variations in incidence depending on the measurement modality. This emphasizes the need for a 'gold standard' of measurement of LLL in clinical practice and research.

Long term survival outcomes of stage I mucinous ovarian cancer - A clinical calculator predictive of chemotherapy benefit.

OBJECTIVES: To determine the long-term potential benefit of adjuvant chemotherapy in subgroups of high-risk stage I mucinous ovarian cancer patients using a predictive scoring algorithm. METHODS: Data were collected from the National Cancer Database from 2004 to 2014. Based on demographic and surgical characteristics, a novel 10-year survival prognostic scoring system was developed using Cox regression. RESULTS: There were 2041 eligible patients with stage I mucinous ovarian cancer including 1362 (67%) with stage IA/IB disease, 598 (29%) with stage IC disease, and 81 (4%) with stage I disease not otherwise specified. Median age was 52 with a range of 13-90 years old. 737 (36%) patients were treated with adjuvant chemotherapy. Adjuvant chemotherapy was more common in patients with stage IC relative to stage IA/IB disease (69% vs. 21%, P < 0.001) or with poorly-differentiated relative to well-differentiated tumors (69% vs. 23%, P < 0.001). Unadjusted 10-year survival was 81% relative to 79% for patients treated with vs. without chemotherapy, respectively (P = 0.46). Patients were predicted to exhibit a low- or a high-risk of death using a multivariate Cox regression model with age, stage, grade, lymphovascular space invasion and ascites. Risk of death without vs. with adjuvant chemotherapy was similar in low-risk patients (88% vs. 84%; HR = 0.80, 95%CI = 0.56-1.15, P = 0.23) and worse in high-risk patients (51% vs. 74%; HR = 1.58, 95%CI: 1.05-2.38, P = 0.03) with stage I mucinous ovarian cancer. CONCLUSIONS: A predictive scoring algorithm may provide prognostic information on long-term survival and identify high-risk stage I mucinous ovarian cancer patients who might achieve a survival benefit from adjuvant chemotherapy.

Hormone Therapy Use After Premature Surgical Menopause Based on Prescription Records: A Population-Based Study.

OBJECTIVE: Premature surgical menopause (PSM) without subsequent hormone replacement therapy (HRT) can lead to morbidity and mortality. Our objective was to describe the use of HRT following PSM and identify variables associated with HRT use based on prescription records from a population-based cohort. METHODS: A population-based retrospective cohort of women in British Columbia, Canada who underwent PSM between the ages of 19 and 49 years. Women were identified using surgical data from the Discharge Abstract Database and linked to HRT prescription histories from the BC PharmaNet database for the period of 2004 to 2014. HRT prescription rates were calculated, and factors associated with postoperative HRT use were identified. RESULTS: A total of 12 837 women were included, with a median age of 43 years. They had undergone BSO with concurrent hysterectomy (49.9%). bilateral salpingo-oophorectomy (BSO) alone (42.1%), or bilateral oophorectomy (BO) (8%). The most common indications for surgery were endometriosis (17.9%), benign adnexal neoplasm (17.2%), and abnormal bleeding (14.0%). Only 55.3% of women ever used HRT, and 47.9% of these women used HRT for less than 1 year. HRT use was higher among women who underwent concurrent hysterectomy (60.7% vs. 50%, P < 0.001). This association remained significant after multivariate adjustment (aOR 1.64; 95% CI 1.50-1.79). Women with a known BRCA mutation were also more likely to use HRT postoperatively (aOR 3.73; 95% CI 2.14-6.81). CONCLUSION: In this large population-based study, HRT use after PSM was 50%. Our study highlights the need for education of both health care providers and patients, and for ongoing follow-up in this young population.