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Cancer Prevention Research... Nov 2021Without preventive interventions, women with germline pathogenic variants in or have high lifetime risks for breast cancer and tubo-ovarian cancer. The increased risk... (Review)
Review
Without preventive interventions, women with germline pathogenic variants in or have high lifetime risks for breast cancer and tubo-ovarian cancer. The increased risk for breast cancer starts at a considerably younger age than that for tubo-ovarian cancer. Risk-reducing bilateral salpingo-oophorectomy (rrBSO) is effective in reducing tubo-ovarian cancer risk for and mutation carriers, but whether it reduces breast cancer risk is less clear. All studies of rrBSO and breast cancer risk are observational in nature and subject to various forms of bias and confounding, thus limiting conclusions that can be drawn about causation. Early studies supported a statistically significant protective association for rrBSO on breast cancer risk, which is reflected by several international guidelines that recommend consideration of premenopausal rrBSO for breast cancer risk reduction. However, these historical studies were hampered by the presence of several important biases, including immortal person-time bias, confounding by indication, informative censoring, and confounding by other risk factors, which may have led to overestimation of any protective benefit. Contemporary studies, specifically designed to reduce some of these biases, have yielded contradictory results. Taken together, there is no clear and consistent evidence for a role of premenopausal rrBSO in reducing breast cancer risk in or mutation carriers.
Topics: BRCA1 Protein; BRCA2 Protein; Breast Neoplasms; Female; Genetic Predisposition to Disease; Humans; Mutation; Ovarian Neoplasms; Ovariectomy; Risk; Salpingo-oophorectomy
PubMed: 34348913
DOI: 10.1158/1940-6207.CAPR-21-0141 -
International Journal of Gynecological... Jun 2023Risk-reducing salpingectomy with delayed oophorectomy has gained interest for individuals at high risk for tubo-ovarian cancer as there is compelling evidence that...
TUBectomy with delayed oophorectomy as an alternative to risk-reducing salpingo-oophorectomy in high-risk women to assess the safety of prevention: the TUBA-WISP II study protocol.
BACKGROUND
Risk-reducing salpingectomy with delayed oophorectomy has gained interest for individuals at high risk for tubo-ovarian cancer as there is compelling evidence that especially high-grade serous carcinoma originates in the fallopian tubes. Two studies have demonstrated a positive effect of salpingectomy on menopause-related quality of life and sexual health compared with standard risk-reducing salpingo-oophorectomy.
PRIMARY OBJECTIVE
To investigate whether salpingectomy with delayed oophorectomy is non-inferior to the current standard salpingo-oophorectomy for the prevention of tubo-ovarian cancer among individuals at high inherited risk.
STUDY HYPOTHESIS
We hypothesize that postponement of oophorectomy after salpingectomy, to the age of 40-45 () or 45-50 () years, compared with the current standard salpingo-oophorectomy at age 35-40 () or 40-45 () years, is non-inferior in regard to tubo-ovarian cancer risk.
TRIAL DESIGN
In this international prospective preference trial, participants will choose between the novel salpingectomy with delayed oophorectomy and the current standard salpingo-oophorectomy. Salpingectomy can be performed after the completion of childbearing and between the age of 25 and 40 (), 25 and 45 (), or 25 and 50 ( and pathogenic variant carriers) years. Subsequent oophorectomy is recommended at a maximum delay of 5 years beyond the upper limit of the current guideline age for salpingo-oophorectomy. The current National Comprehensive Cancer Network (NCCN) guideline age, which is also the recommended age for salpingo-oophorectomy within the study, is 35-40 years for , 40-45 years for and 45-50 years for , , and pathogenic variant carriers.
MAJOR INCLUSION/EXCLUSION CRITERIA
Premenopausal individuals with a documented class IV or V germline pathogenic variant in the or gene who have completed childbearing are eligible for participation. Participants may have a personal history of a non-ovarian malignancy.
PRIMARY ENDPOINT
The primary outcome is the cumulative tubo-ovarian cancer incidence at the target age: 46 years for and 51 years for pathogenic variant carriers.
SAMPLE SIZE
The sample size to ensure sufficient power to test non-inferiority of salpingectomy with delayed oophorectomy compared with salpingo-oophorectomy requires 1500 and 1500 pathogenic variant carriers.
ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS
Participant recruitment is expected to be completed at the end of 2026 (total recruitment period of 5 years). The primary outcome is expected to be available in 2036 (minimal follow-up period of 10 years).
TRIAL REGISTRATION NUMBER
NCT04294927.
Topics: Humans; Female; Adult; Middle Aged; Child, Preschool; Salpingo-oophorectomy; Prospective Studies; Quality of Life; Genes, BRCA1; Mutation; Ovariectomy; Salpingectomy; BRCA1 Protein; Ovarian Neoplasms; Genetic Predisposition to Disease
PubMed: 37045546
DOI: 10.1136/ijgc-2023-004377 -
Gynecologic Oncology Reports Aug 2022Investigate the impact of the COVID-19 pandemic on risk-reducing salpingo-oophorectomies (RRSO) consults.
OBJECTIVE
Investigate the impact of the COVID-19 pandemic on risk-reducing salpingo-oophorectomies (RRSO) consults.
METHODS
Survey sent out to 1,127 full members of the Society of Gynecologic Oncology in August 2021. Survey data included physician characteristics, practice location, and self-reported subjective and objective data about their RRSO consults.
RESULTS
We received 70 responses; half of the respondents were female; the mean age of respondents was 46 (range 35-65). 86% of providers transitioned RRSO consults to telehealth. There was no correlation between uptake of telemedicine by age (R = 0.09) or gender (p = 0.80), but there was increased use in the West Coast region (p < 0.01). There was a small decrease in average time spent discussing sexual function over telehealth (35 s). Most providers felt comfortable discussing sexual health and function via telehealth.
CONCLUSIONS
Overall, telemedicine is now commonly used for RRSO consults and physicians noted very few barriers to its uptake. Discussion of sexual function was similar between modalities, the loss of the pelvic exam or private setting did not affect the time providers spent discussing sexual health, however sexual health topics discussed were limited.
PubMed: 35782580
DOI: 10.1016/j.gore.2022.101036 -
Sexual Medicine Jun 2018Women after risk-reducing salpingo-oophorectomy (RRSO) can have impaired sexual functioning, but whether there is an association between hormone levels and sexual...
INTRODUCTION
Women 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.
AIM
To determine whether hormone levels are associated with sexual functioning in women after RRSO.
METHODS
This 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 MEASURES
Associations with sexual pleasure and sexual discomfort scores were expressed by multivariable regression coefficients and associations with sexual activity were expressed by odds ratios.
RESULTS
None 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.
CONCLUSIONS
Our 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.
PubMed: 29631858
DOI: 10.1016/j.esxm.2018.02.002 -
BMJ (Clinical Research Ed.) Dec 2021To determine if bilateral salpingo-oophorectomy, compared with ovarian conservation, is associated with all cause or cause specific death in women undergoing...
OBJECTIVES
To determine if bilateral salpingo-oophorectomy, compared with ovarian conservation, is associated with all cause or cause specific death in women undergoing hysterectomy for non-malignant disease, and to determine how this association varies with age at surgery.
DESIGN
Population based cohort study.
SETTING
Ontario, Canada from 1 January 1996 to 31 December 2015, and follow-up to 31 December 2017.
PARTICIPANTS
200 549 women (aged 30-70 years) undergoing non-malignant hysterectomy, stratified into premenopausal (<45 years), menopausal transition (45-49 years), early menopausal (50-54 years), and late menopausal (≥55 years) groups according to age at surgery; median follow-up was 12 years (interquartile range 7-17).
EXPOSURES
Bilateral salpingo-oophorectomy versus ovarian conservation.
MAIN OUTCOMES MEASURES
The primary outcome was all cause death. Secondary outcomes were non-cancer and cancer death. Within each age group, overlap propensity score weighted survival models were used to examine the association between bilateral salpingo-oophorectomy and mortality outcomes, while adjusting for demographic characteristics, gynaecological conditions, and comorbidities. To account for comparisons in four age groups, P<0.0125 was considered statistically significant.
RESULTS
Bilateral salpingo-oophorectomy was performed in 19%, 41%, 69%, and 81% of women aged <45, 45-49, 50-54, and ≥55 years, respectively. The procedure was associated with increased rates of all cause death in women aged <45 years (hazard ratio 1.31, 95% confidence interval 1.18 to 1.45, P<0.001; number needed to harm 71 at 20 years) and 45-49 years (1.16, 1.04 to 1.30, P=0.007; 152 at 20 years), but not in women aged 50-54 years (0.83, 0.72 to 0.97, P=0.018) or ≥55 years (0.92, 0.82 to 1.03, P=0.16). Findings in women aged <50 years were driven largely by increased non-cancer death. In secondary analyses identifying a possible change in the association between bilateral salpingo-oophorectomy and all cause death with advancing age at surgery, the hazard ratio gradually decreased during the menopausal transition and remained around 1 at all ages thereafter.
CONCLUSION
In this observational study, bilateral salpingo-oophorectomy at non-malignant hysterectomy appeared to be associated with increased all cause mortality in women aged <50 years, but not in those aged ≥50 years. While caution is warranted when considering bilateral salpingo-oophorectomy in premenopausal women without indication, this strategy for ovarian cancer risk reduction does not appear to be detrimental to survival in postmenopausal women.
Topics: Adult; Age Factors; Aged; Cohort Studies; Fallopian Tube Neoplasms; Female; Humans; Middle Aged; Ontario; Ovarian Neoplasms; Peritoneal Neoplasms; Salpingo-oophorectomy; Survival Analysis
PubMed: 34880044
DOI: 10.1136/bmj-2021-067528 -
Annals of Surgical Oncology Sep 2023The objective of this study was to compare postoperative complication rates and healthcare charges between patients who underwent coordinated versus staged breast...
BACKGROUND
The objective of this study was to compare postoperative complication rates and healthcare charges between patients who underwent coordinated versus staged breast surgery and bilateral salpingo-oophorectomy (BSO).
PATIENTS AND METHODS
The MarketScan administrative database was used to identify adult female patients with invasive breast cancer or BRCA1/BRCA2 mutations who underwent BSO and breast surgery (lumpectomy or mastectomy with or without reconstruction) between 2010 and 2015. Patients were assigned to the coordinated group if a breast operation and BSO were performed simultaneously or assigned to the staged group if BSO was performed separately. Primary outcomes were (1) incidence of 90-day postoperative complications and (2) 2-year aggregate perioperative healthcare charges. Fisher's exact tests, Wilcoxon rank-sum tests, and multivariable regression analyses were performed.
RESULTS
Of the 4228 patients who underwent breast surgery and BSO, 412 (9.7%) were in the coordinated group and 3816 (90.3%) were in the staged group. The coordinated group had a higher incidence of postoperative complications (24.0% vs. 17.7%, p < 0.01), higher risk-adjusted odds of postoperative complications [odds ratio (OR) 1.37, 95% confidence interval (CI) 1.06-1.76, p = 0.02], and similar aggregate healthcare charges before (median charges: $106,500 vs. $101,555, p = 0.96) and after risk-adjustment [incidence rate ratio (IRR) 1.00, 95% CI 0.93-1.07; p = 0.95]. In a subgroup analysis, incidence of postoperative complications (12.9% for coordinated operations vs. 11.7% for staged operation, p = 0.73) was similar in patients whose breast operation was a lumpectomy.
CONCLUSIONS
While costs were similar, coordinating breast surgery with BSO was associated with more complications in patients who underwent mastectomy, but not in patients who underwent lumpectomy. These data should inform shared decision-making in high-risk patients.
Topics: Adult; Humans; Female; Mastectomy; Salpingo-oophorectomy; Breast Neoplasms; Ovarian Neoplasms; Postoperative Complications; Ovariectomy
PubMed: 37336806
DOI: 10.1245/s10434-023-13630-0 -
Journal of Clinical Oncology : Official... Jun 2022After risk-reducing salpingo-oophorectomy (RRSO), / pathogenic variant (PV) carriers have a residual risk to develop peritoneal carcinomatosis (PC). The etiology of PC... (Meta-Analysis)
Meta-Analysis
PURPOSE
After risk-reducing salpingo-oophorectomy (RRSO), / pathogenic variant (PV) carriers have a residual risk to develop peritoneal carcinomatosis (PC). The etiology of PC is not yet clarified, but may be related to serous tubal intraepithelial carcinoma (STIC), the postulated origin for high-grade serous cancer. In this systematic review and individual patient data meta-analysis, we investigate the risk of PC in women with and without STIC at RRSO.
METHODS
Unpublished data from three centers were supplemented by studies identified in a systematic review of EMBASE, MEDLINE, and the Cochrane library describing women with a -PV with and without STIC at RRSO until September 2020. Primary outcome was the hazard ratio for the risk of PC between -PV carriers with and without STIC at RRSO, and the corresponding 5- and 10-year risks. Primary analysis was based on a one-stage Cox proportional-hazards regression with a frailty term for study.
RESULTS
From 17 studies, individual patient data were available for 3,121 women, of whom 115 had a STIC at RRSO. The estimated hazard ratio to develop PC during follow-up in women with STIC was 33.9 (95% CI, 15.6 to 73.9), < .001) compared with women without STIC. For women with STIC, the five- and ten-year risks to develop PC were 10.5% (95% CI, 6.2 to 17.2) and 27.5% (95% CI, 15.6 to 43.9), respectively, whereas the corresponding risks were 0.3% (95% CI, 0.2 to 0.6) and 0.9% (95% CI, 0.6 to 1.4) for women without STIC at RRSO.
CONCLUSION
-PV carriers with STIC at RRSO have a strongly increased risk to develop PC which increases over time, although current data are limited by small numbers of events.
Topics: Breast Neoplasms; Cystadenocarcinoma, Serous; Fallopian Tube Neoplasms; Female; Heterozygote; Humans; Mutation; Ovarian Neoplasms; Ovariectomy; Peritoneal Neoplasms; Salpingo-oophorectomy
PubMed: 35302882
DOI: 10.1200/JCO.21.02016 -
Archives of Public Health = Archives... Feb 2023In April 2020, insurance coverage for risk-reducing salpingo-oophorectomy (RRSO) for breast cancer patients with hereditary breast and ovarian cancer (HBOC) syndrome and...
BACKGROUND
In April 2020, insurance coverage for risk-reducing salpingo-oophorectomy (RRSO) for breast cancer patients with hereditary breast and ovarian cancer (HBOC) syndrome and BRCA testing were started in Japan. We investigated the impact of insurance coverage on the number of RRSO and BRCA tests performed.
METHODS
The subjects were 370 breast cancer patients and 23 of their relatives who received genetic counseling at our institution between April 2014 and December 2021. Finally, 349 patients and 15 relatives were analyzed. We retrospectively compared the number of BRCA tests, RRSO, insurance status, and co-payment of medical expenses before and after insurance coverage based on medical records.
RESULTS
In the 6-year pre-coverage period, 226 patients (mean: 37/year) received genetic counseling and 106 (17/year) received BRCA testing. In the 21-month post-coverage period, 161 patients (92/year) received genetic counseling and 127 (72/year) received BRCA testing. The rate of testing/counseling significantly increased in the post-coverage period (46.9% vs. 78.8%; p < .001). The number of patients who were diagnosed with HBOC were 24 (4/year) and 18 (10/year) and RRSO was performed for 7 (1/year) and 11 (6/year) patients in the pre- and post-coverage periods, respectively. The rate of RRSO/HBOC was significantly increased in the post-coverage period (29.1% vs. 61.1%; p = 0.039). RRSO patients' co-payment rates decreased from 64% to 25% pre- and post-coverage.
CONCLUSIONS
Our findings suggest that decreased co-payments were the primary reason for these increases. Insurance coverage is an important factor when promoting preventive medical services such as RRSO.
PubMed: 36849964
DOI: 10.1186/s13690-023-01048-9 -
Virchows Archiv : An International... Apr 2022Our understanding of the oncogenesis of high-grade serous cancer of the ovary and its precursor lesions, such as serous tubal intraepithelial carcinoma (STIC), has... (Meta-Analysis)
Meta-Analysis Review
Our understanding of the oncogenesis of high-grade serous cancer of the ovary and its precursor lesions, such as serous tubal intraepithelial carcinoma (STIC), has significantly increased over the last decades. Adequate and reproducible diagnosis of these precursor lesions is important. Diagnosing STIC can have prognostic consequences and is an absolute requirement for safely offering alternative risk reducing strategies, such as risk reducing salpingectomy with delayed oophorectomy. However, diagnosing STIC is a challenging task, possessing only moderate reproducibility. In this review and meta-analysis, we look at how pathologists come to a diagnosis of STIC. We performed a literature search identifying 39 studies on risk reducing salpingo-oophorectomy in women with a known BRCA1/2 PV, collectively reporting on 6833 patients. We found a pooled estimated proportion of STIC of 2.8% (95% CI, 2.0-3.7). We focused on reported grossing protocols, morphological criteria, level of pathologist training, and the use of immunohistochemistry. The most commonly mentioned morphological characteristics of STIC are (1) loss of cell polarity, (2) nuclear pleomorphism, (3) high nuclear to cytoplasmic ratio, (4) mitotic activity, (5) pseudostratification, and (6) prominent nucleoli. The difference in reported incidence of STIC between studies who totally embedded all specimens and those who did not was 3.2% (95% CI, 2.3-4.2) versus 1.7% (95% CI, 0.0-6.2) (p 0.24). We provide an overview of diagnostic features and present a framework for arriving at an adequate diagnosis, consisting of the use of the SEE-FIM grossing protocol, evaluation by a subspecialized gynecopathologist, rational use of immunohistochemical staining, and obtaining a second opinion from a colleague.
Topics: Adenocarcinoma in Situ; Carcinoma in Situ; Cystadenocarcinoma, Serous; Fallopian Tube Neoplasms; Female; Humans; Incidence; Ovarian Neoplasms; Reproducibility of Results; Salpingectomy
PubMed: 34850262
DOI: 10.1007/s00428-021-03244-w -
Gynecologic Oncology Jun 2023Increasing evidence suggests the fallopian tube as the site of origin of BRCA1/2-associated high-grade ovarian cancers. Several ongoing trials are evaluating... (Review)
Review
OBJECTIVE
Increasing evidence suggests the fallopian tube as the site of origin of BRCA1/2-associated high-grade ovarian cancers. Several ongoing trials are evaluating salpingectomy with delayed oophorectomy (RRSDO) for ovarian cancer risk reduction and patients are beginning to ask their clinicians about this surgical option. This study sought to systematically review the available literature examining patient preferences regarding RRSDO and risk-reducing salpingo-oophorectomy (RRSO) to provide clinicians with an understanding of patient values, concerns, and priorities surrounding ovarian cancer risk-reducing surgery.
METHODS
We conducted a systematic review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO No.: CRD42023400690). We searched key electronic databases to identify studies evaluating acceptance and surgical decision-making regarding RRSO and RRSDO among patients with an increased risk of ovarian cancer.
RESULTS
The search yielded 239 results, among which six publications met the systematic review inclusion criteria. Acceptance of RRSDO was evaluated in all studies and ranged from 34% to 71%. Factors positively impacting patients' acceptance of RRSDO included: avoidance of surgical menopause, preservation of fertility, concerns about sexual dysfunction, family history of breast cancer, and avoidance of hormone replacement therapy. Factors limiting this acceptance reported by patients included concerns regarding oncologic safety, surgical timing, and surgical complications.
CONCLUSION
To date, few studies have explored patient perspectives surrounding RRSDO. Collectively, the limited data available indicate a high level of acceptance among BRCA1/2 carriers, and provides insight regarding both facilitating and limiting factors associated with patient preferences to better equip clinicians in the counseling and support of their patients.
Topics: Humans; Female; BRCA1 Protein; BRCA2 Protein; Ovariectomy; Salpingectomy; Ovarian Neoplasms; Breast Neoplasms; Risk Reduction Behavior; Mutation; Genetic Predisposition to Disease
PubMed: 37116391
DOI: 10.1016/j.ygyno.2023.04.006