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Cancers Mar 2023Risk-reducing salpingo-oophorectomy (RRSO) is the gold standard method of ovarian cancer risk reduction, but the data are conflicting regarding the impact on breast... (Review)
Review
BACKGROUND
Risk-reducing salpingo-oophorectomy (RRSO) is the gold standard method of ovarian cancer risk reduction, but the data are conflicting regarding the impact on breast cancer (BC) outcomes. This study aimed to quantify BC risk/mortality in / carriers after RRSO.
METHODS
We conducted a systematic review (CRD42018077613) of / carriers undergoing RRSO, with the outcomes including primary BC (PBC), contralateral BC (CBC) and BC-specific mortality (BCSM) using a fixed-effects meta-analysis, with subgroup analyses stratified by mutation and menopause status.
RESULTS
RRSO was not associated with a significant reduction in the PBC risk (RR = 0.84, 95%CI: 0.59-1.21) or CBC risk (RR = 0.95, 95%CI: 0.65-1.39) in and carriers combined but was associated with reduced BC-specific mortality in BC-affected and carriers combined (RR = 0.26, 95%CI: 0.18-0.39). Subgroup analyses showed that RRSO was not associated with a reduction in the PBC risk (RR = 0.89, 95%CI: 0.68-1.17) or CBC risk (RR = 0.85, 95%CI: 0.59-1.24) in carriers nor a reduction in the CBC risk in carriers (RR = 0.35, 95%CI: 0.07-1.74) but was associated with a reduction in the PBC risk in carriers (RR = 0.63, 95%CI: 0.41-0.97) and BCSM in BC-affected carriers (RR = 0.46, 95%CI: 0.30-0.70). The mean NNT = 20.6 RRSOs to prevent one PBC death in carriers, while 5.6 and 14.2 RRSOs may prevent one BC death in BC-affected and carriers combined and carriers, respectively.
CONCLUSIONS
RRSO was not associated with PBC or CBC risk reduction in and carriers combined but was associated with improved BC survival in BC-affected and carriers combined and carriers and a reduced PBC risk in carriers.
PubMed: 36900415
DOI: 10.3390/cancers15051625 -
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 -
CMAJ : Canadian Medical Association... Nov 2021
Topics: Canada; Combined Modality Therapy; Early Detection of Cancer; Endometrial Neoplasms; Female; Humans; Hysterectomy; Neoplasm Grading; Neoplasm Staging; Risk Factors; Salpingo-oophorectomy
PubMed: 34782385
DOI: 10.1503/cmaj.202731-f -
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 -
Cancers May 2021In the field of gynecology, the approval of the PARP inhibitors (PARPi) has been changing the treatment of ovarian cancer patients. The genetic test and the HRD test... (Review)
Review
In the field of gynecology, the approval of the PARP inhibitors (PARPi) has been changing the treatment of ovarian cancer patients. The genetic test and the HRD test are being used as a companion diagnosis before starting PARPi treatment. BRACAnalysis CDx and Myriad myChoice HRD test are widely used as a BRCA genetic test and HRD test, respectively. In addition, FoundationOneCDx is sometimes used as a tumor BRCA test and HRD test. In clinical practice, gynecologists treating ovarian cancer are faced with making decisions such as whether to recommend the g test to all ovarian cancer patients, whether to perform the g test first or HRD test first, and so on. Regarding the judgment result of the HRD test, the cutoff value differs depending on the clinical trial, and the prevalence of g pathogenic variant rate is different in each histological type and country. A prospective cohort study showed that RRSO reduced all-cause mortality in both pre- and postmenopausal women; however, RRSO significantly reduced the risk of breast cancer for 2 pathogenic variant carriers, but not for 1 pathogenic variant carriers. Moreover, salpingectomy alone is said to not decrease the risk of developing ovarian or breast cancer, so further discussion is evidently required. We discuss the current situation and problems in doing genetic test and RRSO in this review article.
PubMed: 34071148
DOI: 10.3390/cancers13112562 -
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 -
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 -
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 -
Journal of Clinical Medicine May 2022This systematic review identifies, evaluates, and summarises the findings of all relevant individual studies on the prevalence of BRCA mutation (BRCAm) in endometrial... (Review)
Review
This systematic review identifies, evaluates, and summarises the findings of all relevant individual studies on the prevalence of BRCA mutation (BRCAm) in endometrial cancer patients and the incidence of endometrial cancer in BRCAm women patients. Consequently, the benefits and limits of a prophylactic hysterectomy at the time of the risk-reducing salpingo-oophorectomy are analysed and discussed. A systematic literature search was performed in the databases of PubMed, Cochrane, and Web of Science until May 2022; 13 studies met the eligibility criteria. Overall, 1613 endometrial cancer patients from 11 cohorts were tested for BRCA1/2 mutation. BRCA1/2m were identified in 4.3% of women with endometrial cancer (70/1613). BRCA1m was the most represented (71.4%) pathogenic variant. Alongside, a total of 209 BRCAm carriers from 14 studies were diagnosed with endometrial cancer. Only 5 out of 14 studies found a correlation between BRCAm and an increased risk of endometrial cancer. Nevertheless, two studies found a statistical difference only for BRCA1m women. The present systematic review does not provide strong evidence in favour of performing routine hysterectomy at the time of risk-reducing salpingo-oophorectomy; however, it provides epidemiological data that can be useful for counselling patients in order to offer a tailored approach.
PubMed: 35683509
DOI: 10.3390/jcm11113114