Objective: To study the impact of premenopausal risk-reducing salpingo-oophorectomy (RRSO), compared with postmenopausal RRSO, on urinary incontinence (UI) >= 10 years later.Design: Cross... Show moreObjective: To study the impact of premenopausal risk-reducing salpingo-oophorectomy (RRSO), compared with postmenopausal RRSO, on urinary incontinence (UI) >= 10 years later.Design: Cross-sectional study, nested in a nationwide cohort.Setting: Multicentre in the Netherlands.Population: 750 women (68% BRCA1/2 pathogenic variant carriers) who underwent either premenopausal RRSO (<= 45 years, n = 496) or postmenopausal RRSO (>= 54 years, n = 254). All participants were >= 55 years at the time of the study.Methods: Urinary incontinence was assessed by the urinary distress inventory-6 (UDI-6); a score >= 33.3 indicated symptomatic UI. The incontinence impact questionnaire short form (IIQ-SF) was used to assess the impact on women's health-related quality of life (HR-QoL). Differences between groups were analysed using regression analyses adjusting for current age and other confounders.Main outcome measures: Differences in UDI-6 scores and IIQ-SF scores between women with a premenopausal and a postmenopausal RRSO.Results: Women in the premenopausal RRSO group had slightly higher UDI-6 scores compared with women in the postmenopausal RRSO group (P = 0.053), and their risk of symptomatic UI was non-significantly increased (odds ratio [OR] 2.1, 95% confidence interval [95% CI] 0.93-4.78). A premenopausal RRSO was associated with a higher risk of stress UI (OR 3.5, 95% CI 1.2-10.0) but not with urge UI. The proportions of women with a significant impact of UI on HR-QoL were similar in the premenopausal and postmenopausal RRSO groups (10.4% and 13.0%, respectively; P = 0.46).Conclusions: More than 15 years after premenopausal RRSO, there were no significant differences in overall symptomatic UI between women with a premenopausal and those with a postmenopausal RRSO. Show less
Terra, L.; Beekman, M.J.; Engelhardt, E.G.; Heemskerk-Gerritsen, B.A.M.; Beurden, M. van; Lennep, J.E.R. van; ... ; Leeuwen, F.E. van 2023
BACKGROUND: Women with a BRCA1/2 pathogenic variant are advised to undergo premenopausal risk-reducing salpingo-oophorectomy after completion of childbearing, to reduce their risk of ovarian cancer... Show moreBACKGROUND: Women with a BRCA1/2 pathogenic variant are advised to undergo premenopausal risk-reducing salpingo-oophorectomy after completion of childbearing, to reduce their risk of ovarian cancer. Several studies reported less sexual pleasure 1 to 3 years after a pre-menopausal oophorectomy. However, the long-term effects of premeno-pausal oophorectomy on sexual functioning are unknown.OBJECTIVE: This study aimed to study long-term sexual functioning in women at increased familial risk of breast or ovarian cancer who under-went a risk-reducing salpingo-oophorectomy either before the age of 46 years (premenopausal group) or after the age of 54 years (postmenopausal group). Subgroup analyses were performed in the premenopausal group, comparing early (before the age of 41 years) and later (at ages 41-45 years) premenopausal risk-reducing salpingo-oophorectomy.STUDY DESIGN: Between 2018 and 2021, 817 women with a high familial risk of breast or ovarian cancer from an ongoing cohort study were invited to participate in our study. Because of a large difference in age in the study between the premenopausal and postmenopausal salpingo-oophorectomy groups, we restricted the comparison of sexual func-tioning between the groups to 368 women who were 60 to 70 years old at completion of the questionnaire (226 in the premenopausal group and 142 in the postmenopausal group). In 496 women with a premenopausal risk -reducing salpingo-oophorectomy, we compared the sexual functioning between women in the early premenopausal group (n=151) and women in the later premenopausal group (n=345). Differences between groups were analyzed using multiple regression analyses, adjusting for current age, breast cancer history, use of hormone replacement therapy, body mass index, chronic medication use (yes or no), and body image. RESULTS: Mean times since risk-reducing salpingo-oophorectomy were 20.6 years in the premenopausal group and 10.6 years in the postmenopausal group (P<.001). The mean age at questionnaire completion was 62.7 years in the premenopausal group, compared with 67.0 years in the postmenopausal group (P<.001). Compared with 48.9% of women in the postmenopausal group, 47.4% of women in the pre-menopausal group were still sexually active (P=.80). Current sexual pleasure scores were the same for women in the premenopausal group and women in the postmenopausal group (mean pleasure score, 8.6; P=.99). However, women in the premenopausal group more often re-ported substantial discomfort than women in the postmenopausal group (35.6% vs 20.9%; P=.04). After adjusting for confounders, premeno-pausal risk-reducing salpingo-oophorectomy was associated with sub-stantially more discomfort during sexual intercourse than postmenopausal risk-reducing salpingo-oophorectomy (odds ratio, 3.1; 95% confidence interval, 1.04-9.4). Moreover, after premenopausal risk-reducing sal-pingo-oophorectomy, more severe complaints of vaginal dryness were observed (odds ratio, 2.6; 95% confidence interval, 1.4-4.7). Women with a risk-reducing salpingo-oophorectomy before the age of 41 years reported similar pleasure and discomfort scores as women with a risk -reducing salpingo-oophorectomy between ages 41 and 45 years.CONCLUSION: More than 15 years after premenopausal risk-reducing salpingo-oophorectomy, the proportion of sexually active women was com-parable with the proportion of sexually active women with a postmenopausal risk-reducing salpingo-oophorectomy.However, after a premenopausal risk -reducing salpingo-oophorectomy, women experienced more vaginal dryness and more often had substantial sexual discomfort during sexual intercourse. This did not lead to less pleasure with sexual activity. Show less
Objective: To examine the effect of a premenopausal risk-reducing salpingo-oophorectomy (RRSO) in women at increased risk of ovarian cancer on objective and subjective cognition at least 10 years... Show moreObjective: To examine the effect of a premenopausal risk-reducing salpingo-oophorectomy (RRSO) in women at increased risk of ovarian cancer on objective and subjective cognition at least 10 years after RRSO.Design: A cross-sectional study with prospective follow-up, nested in a nationwide cohort.Setting: Multicentre in the Netherlands.Population or Sample: 641 women (66% BRCA1/2 pathogenic variant carriers) who underwent either a premenopausal RRSO <= age 45 (n = 436) or a postmenopausal RRSO >= age 54 (n = 205). All participants were older than 55 years at recruitment.Methods: Participants completed an online cognitive test battery and a questionnaire on subjective cognition. We used multivariable regression analyses, adjusting for age, education, breast cancer, hormone replacement therapy, cardiovascular risk factors and depression.Main Outcome Measures: The influence of RRSO on objective and subjective cognition of women with a premenopausal RRSO compared with women with a postmenopausal RRSO.Results: After adjustment, women with a premenopausal RRSO (mean time since RRSO 18.2 years) performed similarly on objective cognitive tests compared with women with a postmenopausal RRSO (mean time since RRSO 11.9 years). However, they more frequently reported problems with reasoning (odds ratio [OR] 1.8, 95% confidence interval [95% CI] 1.1-3.1) and multitasking (OR 1.9, 95% CI 1.1-3.4) than women with a postmenopausal RRSO. This difference between groups disappeared in an analysis restricted to women of comparable ages (60-70 years).Conclusions: Reassuringly, approximately 18 years after RRSO, we found no association between premenopausal RRSO and objective cognition. Show less
Purpose Intensive screening in BRCA1/2 mutation carriers aims to improve breast cancer (BC) prognosis. Our aim is to clarify the prognostic impact of tumor size in BRCA mutation carriers with a pT1... Show morePurpose Intensive screening in BRCA1/2 mutation carriers aims to improve breast cancer (BC) prognosis. Our aim is to clarify the prognostic impact of tumor size in BRCA mutation carriers with a pT1 BC, which is currently unclear. We are especially interested in differences between pT1a, pT1b, and pT1c regarding the prognosis of node-negative breast cancer, the effect of chemotherapy, and the prevalence of lymph node involvement. Methods For this study, BRCA1/2-associated BC patients were selected from a nationwide cohort. Primary outcomes were 10-year overall survival (OS) per pT1a-b-c group and the effect of chemotherapy on prognosis of node-negative BC, using Kaplan-Meier and Cox models. Finally, we evaluated lymph node involvement per pT1a-b-c group. Results 963 women with pT1 BRCA1/2-associated BC diagnosed between 1990 and 2017 were included, of which 679 had pN0 BC. After a median follow-up of 10.5 years, 10-year OS in patients without chemotherapy was 77.1% in pT1cN0 and lower than for pT1aN0 (91.4%, p = 0.119) and pT1bN0 (90.8%, p = 0.024). OS was better with than without chemotherapy for pT1cN0 (91.6% vs. 77.1%, p = 0.001; hazard ratio (HR) 0.56, 95% confidence interval (CI): 0.21-1.48). Lymph node involvement was 24.9% in pT1c, 18.8% in pT1b, and 8.6% in pT1a. Conclusion Smaller tumor size is associated with better OS and less lymph node involvement in pT1 BRCA1/2-associated BC patients. The results suggest that early detection in BRCA1/2 mutation carriers of pT1a/b BC may reduce mortality and the need for systemic therapy. Show less
Akdeniz, D.; Barele, M. van; Heemskerk-Gerritsen, B.A.M.; Steyerberg, E.W.; Hauptmann, M.; Beek, I. van de; ... ; HEBON Investigators 2022
Aim: BRCA1/2 mutation carriers with primary breast cancer (PBC) are at high risk of contralateral breast cancer (CBC). In a nationwide cohort, we investigated the effects of chemotherapeutic agents... Show moreAim: BRCA1/2 mutation carriers with primary breast cancer (PBC) are at high risk of contralateral breast cancer (CBC). In a nationwide cohort, we investigated the effects of chemotherapeutic agents given for PBC on CBC risk separately in BRCA1 and BRCA2 mutation carriers. Patients and methods: BRCA1 or BRCA2 mutation carriers with an invasive PBC diagnosis from 1990 to 2017 were selected from a Dutch cohort. We estimated cumulative CBC incidence using competing risks analysis. Hazard ratios (HR) for the effect of neo-adjuvant or adjuvant chemotherapy and different chemotherapeutic agents on CBC risk were estimated using Cox regression. Results: We included 1090 BRCA1 and 568 BRCA2 mutation carriers; median follow-up was 8.9 and 8.4 years, respectively. Ten-year cumulative CBC incidence for treatment with and without chemotherapy was 6.7% [95%CI: 5.1-8.6] and 16.7% [95%CI: 10.8-23.7] in BRCA1 and 4.8% [95%CI: 2.7-7.8] and 16.0% [95%CI: 9.3-24.4] in BRCA2 mutation carriers, respectively. Chemotherapy was associated with reduced CBC risk in BRCA1 (multivariable HR: 0.46, 95%CI: 0.29-0.74); a similar trend was observed in BRCA2 mutation carriers (HR: 0.63, 95%CI: 0.29-1.39). In BRCA1, risk reduction was most pronounced in the first 5 years (HR: 0.32, 95%CI: 0.17-0.61). Anthracyclines and the combination of anthracyclines with taxanes were associated with substantial CBC risk reduction in BRCA1 carriers (HR: 0.34, 95%CI: 0.17-0.68 and HR: 0.22, 95%CI: 0.08-0.62, respectively). Conclusion: Risk-reducing effects of chemotherapy are substantial for at least 5 years and may be used in personalised CBC risk prediction in any case for BRCA1 mutation carriers. (c) 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Show less
Pre-test counseling about multigene panel testing involves many uncertainties. Ideally, counselees are informed about uncertainties in a way that enables them to make an informed decision about... Show morePre-test counseling about multigene panel testing involves many uncertainties. Ideally, counselees are informed about uncertainties in a way that enables them to make an informed decision about panel testing. It is presently unknown whether and how uncertainty is discussed during initial cancer genetic counseling. We therefore investigated whether and how counselors discuss and address uncertainty, and the extent of shared decision-making (SDM), and explored associations between counselors' communication and their characteristics in consultations on panel testing for cancer. For this purpose, consultations of counselors discussing a multigene panel with a simulated patient were videotaped. Simulated patients represented a counselee who had had multiple cancer types, according to a script. Before and afterwards, counselors completed a survey. Counselors' uncertainty expressions, initiating and the framing of expressions, and their verbal responses to scripted uncertainties of the simulated patient were coded by two researchers independently. Coding was done according to a pre-developed coding scheme using The Observer XT software for observational analysis. Additionally, the degree of SDM was assessed by two observers. Correlation and regression analyses were performed to assess associations of communicated uncertainties, responses and the extent of SDM, with counselors' background characteristics. In total, twenty-nine counselors, including clinical geneticists, genetic counselors, physician assistants-in-training, residents and interns, participated of whom working experience varied between 0 and 25 years. Counselors expressed uncertainties mainly regarding scientific topics (94%) and on their own initiative (95%). Most expressions were framed directly (77%), e.g. We don't know, and were emotionally neutral (59%; without a positive/negative value). Counselors mainly responded to uncertainties of the simulated patient by explicitly referring to the uncertainty (69%), without providing space for further disclosure (66%). More experienced counselors provided less space to further disclose uncertainty (p < 0.02), and clinical geneticists scored lower on SDM compared with other types of counselors (p < 0.03). Our findings that counselors mainly communicate scientific uncertainties and use space-reducing responses imply that the way counselors address counselees' personal uncertainties and concerns during initial cancer genetic counseling is suboptimal. Show less
