Risk-reducing hysterectomy and bilateral salpingo-oophorectomy in female heterozygotes of pathogenic mismatch repair variants: a Prospective Lynch Syndrome Database report.
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ABSTRACT: Purpose
To determine impact of risk-reducing hysterectomy and bilateral salpingo-oophorectomy (BSO) on gynecological cancer incidence and death in heterozygotes of pathogenic MMR (path_MMR) variants.Methods
The Prospective Lynch Syndrome Database was used to investigate the effects of gynecological risk-reducing surgery (RRS) at different ages.Results
Risk-reducing hysterectomy at 25 years of age prevents endometrial cancer before 50 years in 15%, 18%, 13%, and 0% of path_MLH1, path_MSH2, path_MSH6, and path_PMS2 heterozygotes and death in 2%, 2%, 1%, and 0%, respectively. Risk-reducing BSO at 25 years of age prevents ovarian cancer before 50 years in 6%, 11%, 2%, and 0% and death in 1%, 2%, 0%, and 0%, respectively. Risk-reducing hysterectomy at 40 years prevents endometrial cancer by 50 years in 13%, 16%, 11%, and 0% and death in 1%, 2%, 1%, and 0%, respectively. BSO at 40 years prevents ovarian cancer before 50 years in 4%, 8%, 0%, and 0%, and death in 1%, 1%, 0%, and 0%, respectively.Conclusion
Little benefit is gained by performing RRS before 40 years of age and premenopausal BSO in path_MSH6 and path_PMS2 heterozygotes has no measurable benefit for mortality. These findings may aid decision making for women with LS who are considering RRS.
SUBMITTER: Dominguez-Valentin M
PROVIDER: S-EPMC8026395 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:PurposeThis study aimed to report the uptake of hysterectomy and/or bilateral salpingo-oophorectomy (BSO) to prevent gynaecological cancers (risk-reducing surgery [RRS]) in carriers of pathogenic MMR (path_MMR) variants.MethodsThe Prospective Lynch Syndrome Database (PLSD) was used to investigate RRS by a cross-sectional study in 2292 female path_MMR carriers aged 30-69 years.ResultsOverall, 144, 79, and 517 carriers underwent risk-reducing hysterectomy, BSO, or both combined, respectively. Two-thirds of procedures before 50 years of age were combined hysterectomy and BSO, and 81% of all procedures included BSO. Risk-reducing hysterectomy was performed before age 50 years in 28%, 25%, 15%, and 9%, and BSO in 26%, 25%, 14% and 13% of path_MLH1, path_MSH2, path_MSH6, and path_PMS2 carriers, respectively. Before 50 years of age, 107 of 188 (57%) BSO and 126 of 204 (62%) hysterectomies were performed in women without any prior cancer, and only 5% (20/392) were performed simultaneously with colorectal cancer (CRC) surgery.ConclusionUptake of RRS before 50 years of age was low, and RRS was rarely undertaken in association with surgical treatment of CRC. Uptake of RRS aligned poorly with gene- and age-associated risk estimates for endometrial or ovarian cancer that were published recently from PLSD and did not correspond well with current clinical guidelines. The reasons should be clarified. Decision-making on opting for or against RRS and its timing should be better aligned with predicted risk and mortality for endometrial and ovarian cancer in Lynch syndrome to improve outcomes.
| S-EPMC8916840 | biostudies-literature
Project description:Little is known about hysterectomy and bilateral salpingo-oophorectomy (BSO), which are associated with both health risks and benefits, among women Veterans.To compare the prevalence of hysterectomy with or without BSO, and early hysterectomy, between postmenopausal Veterans and non-Veterans.We used baseline data from the Women's Health Initiative Clinical Trial and Observational Study. Multinomial logistic regression models examined differences in the prevalence of hysterectomy (neither hysterectomy nor BSO, hysterectomy without BSO, and hysterectomy with BSO) between Veterans and non-Veterans. Generalized linear models were used to determine whether early hysterectomy (before age 40) differed between Veterans and non-Veterans. Analyses were stratified by birth cohort (<65, ?65 years at enrollment).The unadjusted prevalence of hysterectomy without BSO was similar among Veterans and non-Veterans in both birth cohorts (<65: 22% vs 21%; ?65: 22% vs 21%). The unadjusted prevalence of hysterectomy with BSO was equivalent among Veterans and non-Veterans in the >65 cohort (21%), but higher among Veterans in the <65 cohort (22% vs 19%). In adjusted analyses, although no differences were observed in the >65 cohort, Veterans in the <65 cohort had higher odds of hysterectomy without BSO (odds ratio [OR] 1.18, 95% confidence interval [CI] 1.03, 1.36) and with BSO (OR 1.26, 95% CI 1.10, 1.45), as well as elevated risk of early hysterectomy (relative risk 1.32, 95% CI 1.19, 1.47), compared with non-Veterans.Aging women Veterans may have higher prevalence of hysterectomy and BSO than non-Veterans. This information contributes to understanding the health needs and risks of women Veterans and can inform clinical practice and policy for this population.
| S-EPMC5881615 | biostudies-literature
Project description:Importance:The link between BRCA mutations and uterine cancer is unclear. Therefore, although risk-reducing salpingo-oophorectomy (RRSO) is standard treatment among women with BRCA mutations (BRCA+ women), the role of concomitant hysterectomy is controversial. Objective:To determine the risk for uterine cancer and distribution of specific histologic subtypes in BRCA+ women after RRSO without hysterectomy. Design, Setting, and Participants:This multicenter prospective cohort study included 1083 women with a deleterious BRCA1 or BRCA2 mutation identified from January 1, 1995, to December 31, 2011, at 9 academic medical centers in the United States and the United Kingdom who underwent RRSO without a prior or concomitant hysterectomy. Of these, 627 participants were BRCA1+; 453, BRCA2+; and 3, both. Participants were prospectively followed up for a median 5.1 (interquartile range [IQR], 3.0-8.4) years after ascertainment, BRCA testing, or RRSO (whichever occurred last). Follow up data available through October 14, 2014, were included in the analyses. Censoring occurred at uterine cancer diagnosis, hysterectomy, last follow-up, or death. New cancers were categorized by histologic subtype, and available tumors were analyzed for loss of the wild-type BRCA gene and/or protein expression. Main Outcomes and Measures:Incidence of uterine corpus cancer in BRCA+ women who underwent RRSO without hysterectomy compared with rates expected from the Surveillance, Epidemiology, and End Results database. Results:Among the 1083 women women who underwent RRSO without hysterectomy at a median age 45.6 (IQR: 40.9 - 52.5), 8 incident uterine cancers were observed (4.3 expected; observed to expected [O:E] ratio, 1.9; 95% CI, 0.8-3.7; P?=?.09). No increased risk for endometrioid endometrial carcinoma or sarcoma was found after stratifying by subtype. Five serous and/or serous-like (serous/serous-like) endometrial carcinomas were observed (4 BRCA1+ and 1 BRCA2+) 7.2 to 12.9 years after RRSO (BRCA1: 0.18 expected [O:E ratio, 22.2; 95% CI, 6.1-56.9; P?<?.001]; BRCA2: 0.16 expected [O:E ratio, 6.4; 95% CI, 0.2-35.5; P?=?.15]). Tumor analyses confirmed loss of the wild-type BRCA1 gene and/or protein expression in all 3 available serous/serous-like BRCA1+ tumors. Conclusions and Relevance:Although the overall risk for uterine cancer after RRSO was not increased, the risk for serous/serous-like endometrial carcinoma was increased in BRCA1+ women. This risk should be considered when discussing the advantages and risks of hysterectomy at the time of RRSO in BRCA1+ women.
| S-EPMC5594920 | biostudies-literature
Project description:ObjectiveTo estimate ovarian and peritoneal cancer rates after hysterectomy with and without salpingo-oophorectomy for benign conditions.MethodsAll patients after hysterectomy for benign disease from 1988 to 2006 in Kaiser Permanente Northern California, an integrated health organization. Incidence rates per 100,000 person-years were calculated.ResultsOf 56,692 patients, the majority (54%) underwent hysterectomy with bilateral salpingo-oophorectomy; 7% had hysterectomy with unilateral salpingo-oophorectomy, and 39% had hysterectomy alone. There were 40 ovarian and eight peritoneal cancers diagnosed during follow-up. Median age at ovarian and peritoneal cancer diagnosis was 50 and 64 years, respectively. Age-standardized rates (per 100,000 person-years) of ovarian or peritoneal cancer were 26.7 (95% confidence interval [CI] 16-37.5) for those with hysterectomy alone, 22.8 (95% CI 0.0-46.8) for hysterectomy and unilateral salpingo-oophorectomy, and 3.9 (95% CI 1.5-6.4) for hysterectomy and bilateral salpingo-oophorectomy. Rates of ovarian cancer were 26.2 (95% CI 15.5-37) for those with hysterectomy alone, 17.5 (95% CI 0.0-39.1) for hysterectomy and unilateral salpingo-oophorectomy, and 1.7 (95% CI 0.4-3) for those with hysterectomy and bilateral salpingo-oophorectomy. Compared with women undergoing hysterectomy alone, those receiving an unilateral salpingo-oophorectomy had a hazard ratio (HR) for ovarian cancer of 0.58 (95% CI 0.18-1.9) and those undergoing bilateral salpingo-oophorectomy had an HR of 0.12 (95% CI 0.05-0.28).ConclusionsThe removal of both ovaries decreases the incidence of ovarian and peritoneal cancers. Removal of one ovary might also decrease the incidence of ovarian cancer but warrants further investigation.Level of evidenceII.
| S-EPMC4624417 | biostudies-literature
Project description:Pathogenic germline variants underlie up to 20% of ovarian cancer (OC) and are associated with varying degrees of risk for OC. For mutations in high-penetrance genes such as BRCA1/2, the role of risk-reducing bilateral salpingo-oophorectomy (RRSO) in cancer prevention is well-established and improves mortality. However, in moderate-penetrance genes where the degree of risk for OC is less precisely defined, the role of RRSO is more controversial. Although national guidelines have evolved to incorporate gene-specific recommendations, studies demonstrate significant variations in practice. Given this, our multidisciplinary group has reviewed the available literature on risk estimates for genes associated with OC, incorporated levels of evidence, and set thresholds for consideration of RRSO. We found that the benefit of RRSO is well-established for pathogenic variants in BRCA1/2 as well as BRIP1 and RAD51C/D where the risk of OC is elevated beyond our threshold for RRSO. In PALB2, RRSO is particularly controversial as newer studies consistently demonstrate an increased risk of OC that is dependent on family history, making uniform recommendations challenging. Additionally, new guidelines for Lynch syndrome provide gene-specific risks, questioning the role of RRSO, and even hysterectomy, for MSH6 and PMS2 mutation carriers. Given these uncertainties, shared decision making should be used around RRSO with discussion of individual risk factors, family history, and adverse effects of surgery and premature menopause. Herein, we provide a clinical guide and counseling points.
| S-EPMC8932494 | biostudies-literature
Project description:ObjectivesThe vaginal surgical approach has not become the standard of care, despite its advantages. The Hominis™ Surgical System is a humanoid shaped robot-assisted system that was designed specifically for robotic vaginal natural orifice transluminal endoscopic surgery (RvNOTES). We aimed to present our experience with the first RvNOTES bilateral salpingo-oophorectomy (BSO) performed by the Hominis system.Study designA two-center prospective study of BSO by RvNOTES in women with nonmalignant indications conducted between August and December 2018. Women older than 18 years were offered to participate. Exclusion criteria included a history of abdominal malignancy, pelvic or abdominal irradiation, Crohn's disease, pelvic inflammatory disease, severe infections in the lower abdomen, active diverticulitis, deep infiltrating recto-vaginal endometriosis, and an active vaginal infection. The primary outcome of the study was the rate of conversion to open or laparoscopic approaches. Secondary outcomes included intra- and postoperative adverse events, operative time, estimated blood loss, length of hospital stay, and 6-week follow-up assessment.ResultsEight women aged 50-70 years with BMI of 19-30 kg/m2 were recruited. All the procedures were completed successfully without conversions to open surgery. No intraoperative complications were observed. Median blood loss was 10 mL (range: 10-50). The median duration of the procedure was 45 min (range: 38-91), and decreased over the study period. Surgeons' usability assessment was very favorable, with a median of 5 on a 1-5 scale. The median visual analog scale (VAS) score was 1 (range: 1-3).ConclusionsThis is the first documentation of a surgery performed via the vagina using robotic instrumentation developed for this purpose. The disruptive technology of RvNOTES, with its fast learning curve, will make gynecological surgeries accessible to more women.
| S-EPMC7379144 | biostudies-literature
Project description:IntroductionWomen after risk-reducing salpingo-oophorectomy (RRSO) can have impaired sexual functioning, but whether there is an association between hormone levels and sexual functioning is unclear.AimTo determine whether hormone levels are associated with sexual functioning in women after RRSO.MethodsThis is a retrospective cohort study of 198 sexually active and 91 inactive women after RRSO. Participants completed the Sexual Activity Questionnaire, questionnaires concerning hormone replacement therapy (HRT), quality of life, care from partner, body image, and comorbidity and provided blood samples. Associations between sexual functioning scores and covariates were examined by linear regression. Variables associated with sexual activity were examined by logistic regression.Main outcome measuresAssociations with sexual pleasure and sexual discomfort scores were expressed by multivariable regression coefficients and associations with sexual activity were expressed by odds ratios.ResultsNone of the hormone levels were associated with sexual pleasure in contrast to age (P = .032), current use of systemic HRT (P = .002), and more care form partner (P < .001). Increased free androgen index (P = .016), more care from partner (P = .017), systemic HRT (P = .002), and no history of cardiovascular disease (P = .001) were associated with less sexual discomfort. The odds ratio of being sexually active increased with younger age, no breast cancer, better quality of life, and more care from partner.ConclusionsOur results indicate that other factors than hormone levels are important for sexual functioning, although systemic HRT can have a positive impact on sexual functioning in women who have undergone RRSO. Testosterone therapy could improve women's sexual functioning after RRSO; however, the inverse association between free androgen levels and sexual discomfort should be addressed in future studies. Johansen N, Liavaag AH, Mørkird L, Michelsen TM. Hormone Levels and Sexual Functioning After Risk-Reducing Salpingo-Oophorectomy. Sex Med 2018;6:143-153.
| S-EPMC5960032 | biostudies-literature
Project description: Not available
| S-EPMC8792973 | biostudies-literature
Project description:There are few data on complications with gender affirming surgery. The aim of this study was to assess peri- and postoperative complications of laparoscopic hysterectomy and mastectomy performed in a single sitting in transgender men. Assessment of intra- and postoperative complications in a series of 65 transgender men (mean age 27, range 18-47) undergoing concomitant mastectomy and laparoscopic hysterectomy with salpingo-oophorectomy. Mean operating time was 292 ± 47 min. Thirty-four (52%) patients experienced complications: 28 (41%) DINDO grade I, 0 DINDO grade 2, 6 (11%) DINDO grade III. The six grade 3 complications consisted of 5 hematomas requiring evacuation after mastectomy and 2 vaginal tears requiring transvaginal repair. Three patients were readmitted within 30 days, all for postoperative bleeding/hematoma. In transgender men, performing laparoscopic hysterectomy and mastectomy at a single sitting has a modest rate of perioperative complications, and may improve resource utilization.
| S-EPMC8580897 | biostudies-literature
Project description:ObjectivesThis study aimed to assess the association between hormone replacement therapy and the incidence of subsequent malignancies in patients who underwent risk-reducing salpingo-oophorectomy and had mutations predisposing them to Müllerian cancers.MethodsThis Institutional Review Board-approved retrospective study was performed at five academic institutions. Women were included if they were age 18-51 years, had one or more confirmed germline highly penetrant pathogenic variants, and underwent risk-reducing salpingo-oophorectomy. Patients with a prior malignancy were excluded. Clinicodemographic data were collected by chart review. Patients with no documented contact for one year prior to study termination were called to confirm duration of hormone use and occurrence of secondary outcomes. Hormone replacement therapy included any combination of estrogen or progesterone.ResultsData were analyzed for 159 women, of which 82 received hormone replacement therapy and 77 did not. In both groups an average of 6 years since risk reduction had passed. The patients treated with hormone replacement therapy did not have a higher risk of subsequent malignancy than those not treated with hormone replacement therapy (6 out of 82 vs. 7 out of 77, P = .68). Patients who received hormone replacement therapy were younger than those who did not receive hormone replacement therapy (39.0 vs. 43.9 years, P < .01) and were more likely to have undergone other risk reductive procedures including mastectomy and/or hysterectomy, though this difference was not statistically significant (69.5% vs. 55.8%, P = .07).ConclusionsIn this multi-institution retrospective study of data from patients with high-risk variant carriers who underwent risk-reducing salpingo-oophorectomy, there was no statistically significant difference in the incidence of malignancy between women who did and did not receive hormone replacement therapy.
| S-EPMC8022862 | biostudies-literature