{"paper_id":"3239c698-7488-4dda-9e38-08d563ff6367","body_text":"Factors influencing uptake of risk-reducing mastectomy among unaffected Israeli BRCA1/BRCA2 pathogenic variant carriers | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Factors influencing uptake of risk-reducing mastectomy among unaffected Israeli BRCA1/BRCA2 pathogenic variant carriers Yael Laitman, Karin Aharon, Talia Schloss, Libby Margolin, Eitan Friedman This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8523281/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 10 You are reading this latest preprint version Abstract Women harboring pathogenic variant (PV) in the BRCA1 or BRCA2 genes (= BRCA ) have an elevated lifetime risk for breast cancer (BC). One of the main options for active breast cancer risk reduction is bilateral risk-reducing mastectomy (RRM). Understanding the factors influencing that decision is important for genetic-counselling and risk mitigation strategy planning. A structured questionnaire was circulated to BRCA carriers, members of the Good Genes NGO in Israel. Data on RRM uptake and timing, factors previously reported to be associated with decision to undergo RRM (e.g., psychosocial, family history, counselling/health-system factors) were obtained. Comparison between carriers who elected to undergo RRM with those who opted for early detection schemes were performed using logistic regression and chi square statistical analyses. Of cancer free women (n = 391), 272 (69.6%) elected to adhere to the recommended surveillance scheme and 119 (30.4%) elected to undergo RRM. The major reasons for electing RRM over surveillance were active BC risk reduction (4.96 ± 0.23), fear of developing BC (4.86 ± 0.50), and having at least one relative with BC diagnosed under age 45 years. Support group discussions emerged as a stronger determinant of RRM uptake than primary care physician or religious guidance. In conclusion, among healthy Israeli BRCA carriers the decision to undergo RRM was influenced by a complex interplay of factors – active BC risk reduction, fear of cancer diagnosis in the context of having one relative with early onset BC and support group discussions were the major drivers of RRM in Israeli BRCA1 carriers. BRCA pathogenic variant carriers breast cancer risk risk reducing mastectomy Surveillance decisions Figures Figure 1 Introduction Women harboring pathogenic variants (PVs) in the BRCA1 or BRCA2 genes (= BRCA ) are at a substantially high lifetime risks for developing breast (BC) and ovarian cancer (OvC): for BC these risks are 69–72% and for OvC 17–44% by age 80 years [ 1 ]. Female BRCA carriers are offered an intensified early surveillance scheme aimed at early detection of BC starting at age 25–30 years that include biannual clinical breast exam and breast imaging (MRI alternating with mammograms) [ 2 , 3 ]. For active BC/ OvC risk reduction the only options are risk reducing surgeries – mastectomy (RRM) and salpingo-oophorectomy (RRSO) [ 4 , 5 ]. RRM has been shown to reduce BC incidence by up to 90–95% in BRCA PV carriers [ 6 ]. Thus, RRM is an option that should be discussed during oncogenetic counselling of cancer-free carriers. However, the decision to undergo RRM is complex, irreversible, and involves trade-offs including surgical risks, psychosocial and body‐image consequences, and implications for breast feeding or childbearing timing, especially among young women. Despite the proven effect of RRM on active BC risk reduction, uptake of RRM among unaffected BRCA carriers appears to vary widely across countries and over time. Country-level analyses of more than 6,000 BRCA carriers demonstrated striking international heterogeneity in the uptake of RRM. In the multinational study by Metcalfe et al. [ 7 ], RRM was chosen by 49.9% of U.S. carriers, approximately 40% of U.K. carriers, and only 4.5% of Polish carriers, representing the lowest rate among the ten participating countries. Comparable figures have been reported in large national cohorts: the Danish population-based registry of 3,067 BRCA PV carriers showed 45–55% uptake of RRM [ 8 ], with similar rates reported by a Norwegian national series [ 9 ]. UK prospective data from Evans et al. [ 10 ] confirmed a 47.7% twenty-year uptake of RRM in BRCA carriers. A Czech Republic retrospective cohort [ 11 ] of 496 healthy BRCA PV carriers from a surveillance program (2000–2020) found RRM uptake of ~ 31.5% with a significant increase after 2013 (12% in 2005–12 vs 31.6% in 2013–20). A recent review of 58 studies involving more than 30,000 high-risk women also confirmed wide inter-country variation [ 12 ]. Factors affecting the decision to undergo RRM have been reported to include a wide range of variables: reproductive issues, psychosocial parameters, number of previous breast biopsies, family cancer history and age at cancer diagnosis in relatives, medical and genetic counselling involvement, spouse and family support, and system-level factors (e.g., physician guidance, availability of breast reconstruction, insurance coverage of the procedure) [ 7 , 12 , 13 – 17 ]. Understanding why unaffected carriers elect or decline RRM is essential for optimizing genetic counselling, patient-centered risk communication, and shared decision-making. Specifically in Israel, data on RRM uptake and the factors that guide this decision are sparse. A questionnaire-based, single high-risk clinic study conducted by Laitman et al [ 18 ] among 170 cancer-free BRCA PV carriers reported RRM uptake of 13% (22/170) at follow-up ≥ 18 months. A prior Israeli survey (2004–06) of 99 women (43% carriers) reported ~ 19% of carriers underwent RRM, and ~ 25% had positively considered it [ 19 ]. In this manuscript we explored the factors affecting the decision to undergo RRM in cancer free Israeli BRCA PV carriers using a questionnaire-based data collection scheme. Methods Participants- Israeli women who were all BRCA PV carriers and members of the Good Genes nonprofit organization ( https://goodbrcagenes.org/ ) were eligible for participation. The Good Genes NGO includes carriers from diverse geographic, religious, and socioeconomic backgrounds across Israel, mitigating concerns regarding single-clinic referral bias. After an initial notification of the objectives of the study and explaining the de-identified manner of data collection and analysis, a request for consent to participate was made and obtained. Each consenting participant was sent the questionnaire and returned the filled questionnaire via a secure link. The study protocol was approved by the local Ethics committee (SMC 1492-14). Instrument- Participants completed a structured questionnaire designed to assess factors influencing decisions regarding RRM in BRCA PV carriers. The questionnaire integrated validated domains from prior surveys addressing attitudes toward surgical risk-reduction and preventive strategies in hereditary breast–ovarian cancer syndromes [e.g., 9, 20, 21]. The parameters evaluated included: age at genotyping, mutated gene, reason for genotyping, personal and family cancer history, reproductive variables, perceived cancer risk, body-image concerns, and psychological distress [ 15 , 22 ]. Additional items explored were information sources, cultural and familial influences, medical professionals’ recommendations, and religious beliefs and practices [ 14 , 23 ]. Responses were recorded using 5-point Likert scales (1 = “strongly disagree” to 5 = “strongly agree”) with free-text fields for qualitative insights. The questionnaire was pilot tested in a subset of 25 carriers for clarity and internal consistency before dissemination to the full cohort. Statistical methods Analyses were restricted to women with PVs in BRCA1/BRCA2 who were cancer-free at the time of management decision. The primary comparison was between women choosing RRM and those opting to be managed with surveillance. Age at BRCA carrier diagnosis was treated as a continuous variable. Because age distributions were not assumed to be normal, we used the Mann–Whitney U test to compare age between RRM and surveillance groups [ 24 ]. Extreme outliers in age within the surveillance group were identified using the interquartile range (IQR) method (values < Q1 − 1.5×IQR or > Q3 + 1.5×IQR) and excluded for age-specific descriptive statistics and the age comparison. Family history variables were summarized as both binary indicators (any affected first- or second-degree relative; any first-degree relative with BC or OvC; any first-degree relative with BC < 45 years) and counts of affected relatives. Between-group differences in binary family history variables were evaluated using Pearson’s chi-square tests. For count variables (number of affected first- or second-degree relatives), we reported means, standard deviations, and medians by management group; where formal comparisons were performed, non-parametric tests were preferred given skewed distributions. To account for multiple comparisons across family history variables, p-values from univariate tests were adjusted using the Benjamini–Hochberg false discovery rate (FDR) procedure, and we report both raw p-values and FDR-adjusted q-values [ 25 ]. All tests were two-sided, and statistical significance was a priori defined as q < 0.05. Analyses were additionally stratified by gene ( BRCA1 vs BRCA2 ) to explore whether patterns of age and family history differed by genotype. We used multivariable logistic regression to estimate adjusted odds ratios for undergoing RRM Vs. surveillance, including age at BRCA carrier diagnosis, BRCA1 versus BRCA2 status, and the presence of at least one first-degree relative with BC diagnosed before age 45 years as predictors. Odds ratios were obtained by exponentiating the logistic regression coefficients, providing adjusted effect estimates for each predictor on the likelihood of choosing RRM. Participants rated the influence of multiple decision-related factors on a 1–5 Likert scale (1 = not at all important, 5 = extremely important) [ 26 ], when choosing between RRM and continued surveillance. Items were grouped conceptually into five domains: (1) risk-perception factors (e.g. active BC risk reduction, fear of developing cancer, family history), (2) family-oriented factors (e.g. worrying about the children, not wanting to become a burden on the family), (3) treatment-burden/side-effect concerns (e.g. fear of surgical complications, fear of recovery from surgery, reducing the need for frequent surveillance, preventing frequent biopsies, worry about body image), (4) information-source factors (e.g. information from clinical teams, general internet sources, support group), and (5) religious/spiritual factors (e.g. personal religious beliefs, guidance from a spiritual leader - a rabbi). For each item, we calculated the mean and standard deviation; we then computed domain-level averages to compare the relative influence of these broader constructs. Results A total of 512 single BRCA PV carriers agreed to participate and filled the questionnaire: 308 (60%) were BRCA1 PV carriers and 204 (40%)– BRCA2 PV carriers. Mean age ( ± SD) at data collection was 45.5 ± 10.8 years (range 29–77; median 44 years) and mean ± SD at genotyping and BRCA carriership disclosure 37.9 ± 10.6 (range 25–70; median 37 years). Of participants, 121 were diagnosed with cancer – 102 (84.3%) with BC. Mean age at BC diagnosis 43.5 ± 11.3 years (range 24–68; median 41 years). Among cancer-free BRCA PV carriers, 119 (30%) elected RRM and 272 (70%) chose surveillance. The mean time from genetic test results disclosure to actual RRM was 4.27 ± 4.7 years (range 0–19; median 2 years). Women undergoing RRM were slightly older at BRCA carrier diagnosis than those managed with surveillance (mean 37.6 ± 8.7 vs 35.6 ± 9.8 years; Mann–Whitney U p = 0.017, q = 0.259), after exclusion of age outliers in the surveillance group. Median age at BRCA carrier diagnosis was slightly lower for BRCA1 PV carriers (32 years) than BRCA2 PV carriers (37 years) in the surveillance arm, but these differences were modest and did not translate into large shifts in the relative uptake of RRM versus surveillance by gene. Family history of BC and OvC was highly prevalent in both groups, with no statistically significant differences after multiple-testing correction: ~61% of women in both RRM and surveillance groups had at least one affected first-degree relative (FDR) with BC or OvC, and ~ 38% had an affected FDR with BC. The proportion with an affected FDR with BC before age 45 was numerically higher in the RRM group (about one in five) compared with surveillance, but the difference did not retain statistical significance after FDR correction (q ≥ 0.05), although effect sizes were directionally consistent. Patterns for second-degree relatives (SDR) were similar, with overlapping distributions of the number of affected relatives in both management groups. When stratified by gene, BRCA1 and BRCA2 carriers showed broadly comparable family history profiles within each management strategy. Multivariable logistic regression including age at BRCA carrier diagnosis, mutated BRCA gene, family history variables, global family history measure (any affected FDR, any affected SDR, or the number of affected relatives) was independently associated with undergoing RRM versus surveillance. However, the presence of at least one FDR with BC diagnosed ≤ 45 years of age showed the largest effect size, with higher odds of choosing RRM compared with surveillance. Among BRCA1 PV carriers (n = 218), approximately one-third (32%) underwent RRM. RRM uptake was strongly associated with early-onset family history: only about one-third (32%) of BRCA1 carriers with no FDR diagnosed with BC < 45 years chose RRM, compared with one-half (52%) of those with at least one FDR with BC diagnosed < 45 years of age. The corresponding logistic regression model showed higher predicted probabilities of RRM at younger ages and consistently higher probabilities across age for women with early-onset family history (Fig. 1 ). Among BRCA2 carriers (n = 174), overall RRM uptake was slightly lower, at about one-quarter (26%). As in BRCA1 , early-onset family history was associated with more frequent RRM: only about 25% of BRCA2 PV carriers without an FDR with BC < 45 years underwent RRM, compared with approximately 47% of those with ≥ 1 early-onset BC in FDR. The fitted model for BRCA2 showed the same directional pattern, with higher predicted probabilities of RRM for women with early-onset family history across the age range, although the absolute differences between groups were smaller than in BRCA1 PV carriers. Women opting for RRM had a different distribution of referral reasons — particularly more “family history of cancer” and less “not recorded” than the non-RRM group. This pattern strongly suggests that those choosing RRM were genotyped with clearer and more targeted indications. BRCA1 PV carriers were more likely to undergo RRM compared with BRCA2 PV carriers. This is clinically expected: BRCA1 is associated with higher and earlier BC risk. Women in the RRM group were more likely to have children than those in the non-RRM group. However, the level of effect (as determined by V Cramer) was small-moderate (0.124–0.216) [ 27 ], meaning that these differences had very limited clinical implications or significance. Marital status, level of religious beliefs and practices, and parental origin of the mutation, did not differ significantly between the RRM vs surveillance groups (Table 1 ). Table 1 Comparison of relevant features in RRM Vs surveillance opting groups. Variable RRM (n = 119) Non-RRM (n = 272) p-value Cramer’s V Age at genotyping , mean ± SD (years) 37.6 ± 8.7 35.6 ± 9.8 0.045 ᵃ — Reason for genotyping 0.0004 ᵇ 0.216 Screening 24 54 Mutation in family 42 129 Family history of cancer 52 69 Not recorded 1 20 Marital status 0.505ᵇ 0.059 Married 103 224 Separated/divorced 8 28 Single 8 20 Offspring 0.0145 ᵇ 0.124 Yes 108 218 No 11 54 Religious status 0.497ᵇ 0.060 Orthodox 3 9 Conservative 18 53 Secular 99 210 Mutated gene 0.011 ᵇ 0.128 BRCA1 78 139 BRCA2 41 133 Parental origin of PV 0.313ᵇ 0.077 Maternal 51 97 Paternal 55 134 Unknown 13 41 Footnotes : ᵃ Welch’s t-test. ᵇ χ² test of independence. Bold p-values indicate statistical significance at α = 0.05. Decision-related factors were rated on a 1–5 Likert scale, with higher scores indicating greater influence. When focusing on RRM, the most influential determinants were active BC risk reduction and fear of developing cancer, both with mean scores (4.96 ± 0.23 and 4.86 ± 0.50, respectively). Family-related motivations were also strong: “worrying about my kids” and “not to become a burden on my family” had means of 4.61 ± 1.04 and 4.08 ± 1.32, respectively, indicating that protecting children and avoiding future caregiving burden are major drivers of the choice for RRM. Additional pro-RRM factors with more than moderate influence included efforts to prevent frequent biopsies, and the wish to reduce the need for ongoing surveillance, (ranging between 3.75–3.77). Information from medical teams also contributed meaningfully, with average influence scores in the moderate-to-high range (3.67 ± 1.25). Factors that tended to support continued surveillance rather than RRM were weaker in magnitude. The most prominent surveillance-leaning factors were fear of surgical complications (3.77 ± 1.3), fear of recovery from surgery (3.73 ± 1.36), and worry about body image (3.50 ± 1.39), all of which represent concerns about the immediate and long-term consequences of major surgery. Internet-based and social media information had moderate average influence (means around 3.3), but with large variability between women. The views of family and friends about surgery played a smaller, though non-negligible, role (mean ≈ 2.4). Religious beliefs and guidance from a spiritual leader (rabbi) showed consistently low mean scores (around 1.2). Overall, domain-level analyses show that risk perception and family-oriented motivations dominate the decision landscape, with treatment-burden concerns and information sources exerting moderate influence and religious/spiritual considerations contributing little on average. Notably, women opting for RRM would make the same decision (4.76 ± 0.65), and would recommend other BRCA PV carriers to undergo the same risk reducing surgery (4.55 ± 0.79). Most women opting for surveillance state that they adhere to the recommended scheme (4.69 ± 0.78). Discussion In the current study, the major determinants for opting to undergo RRM in Israeli cancer-free BRCA PV carriers were active BC risk reduction, fear of developing BC, and the wish not to become a burden on the family in case cancer does develop. Additionally, family history of cancer, especially any relative diagnosed with BC < 45 years, primarily in BRCA1 PV carriers genotyped in the 30–50 year age group were more likely to opt for RRM. Notably, the effect of family physician and spiritual leaders – were minimal at best. The findings reported herein from a sizeable cohort of cancer-free Israeli BRCA PV carriers reinforce several well-established determinants previously reported, while adding novel granularity—particularly around family-history sub-patterns, and the minimal influence of primary-care physicians or religious leaders. Prospective psychological evaluations and mixed-methods analyses demonstrate that fear of BC, persistent cancer-related worry, and the perception that RRM provides the most definitive form of risk reduction repeatedly predict surgical decision-making. Isselhard et al., [ 15 ] and Morgan et al., [ 22 ] describe substantial emotional relief following RRM, a contrast to the ongoing anxiety reported by women opting for surveillance. These findings are in line with our data, where BC risk reduction was the highest-ranked motivator and quantitatively measured cancer worry was significantly elevated among women choosing RRM. Similar patterns have been reported in two German prospective cohorts [ 15 , 28 ], higher baseline anxiety, health concerns, and cancer-related distress were independently associated with opting for RRM over intensified surveillance. In a U.S. NCI cohort, Portnoy and coworkers [ 29 ] showed that elevated cancer worry—amplified by false-positive screening experiences—predicted subsequent RRM among BRCA PV carriers, while Padamsee et al., [ 30 ] described that high-risk U.S. women explicitly prioritizing “maximal risk reduction” and “relief from cancer fear” when choosing RRM over chemoprevention or surveillance. Taken together, data from Germany, the United States, and now Israel, indicate that prevention-driven and fear-driven motivations for RRM are remarkably consistent across differing cultural and health-system contexts. Family-history intensity, both in terms of number of affected first-degree relatives and the age at cancer onset has repeatedly been linked with RRM. Gilbert et al. [ 31 ] reported that RRM was more common among women with multiple BCs in FDR and especially when OvC occurred in an FDR before age 40. Singh et al., [ 32 ] similarly showed that having relatives who died of BC significantly influenced the decision for RRM or RRSO. In Dean’s qualitative study of BRCA-positive women [ 33 ], “traumatic family cancer memories” (e.g., watching a mother or aunt die young) were a central source of familial uncertainty and a powerful driver of RRM. Dean and Fisher’s later work [ 34 ] with 46 previvors showed that women who appraise their risk as a “looming danger”— manifesting in vivid memories of early, severe family cancers—are much more likely to choose risk reducing surgery over surveillance as an uncertainty-management strategy. Hoskins and Greene’s study [ 35 ] of young BRCA PV carriers who elected early RRM found that many participants explicitly described surgery as a way to sidestep repeating relatives’ less favorable clinical outcomes and to spare partners and children the experience of “going through cancer again.” These themes are synthesized in Torrisi et al., study [ 36 ] of decision-making for RRM, which highlights family cancer narratives and early losses as core, cross-study motivators for choosing RRM among high-risk women. Our dataset adds further resolution to these previous studies: having an FDR with BC diagnosed < 45 years was particularly pronounced among BRCA1 PV carriers opting for RRM. The rising role of online support groups and BRCA “previvor” communities is also noteworthy. In several cohorts, women who participated in in-person or online BRCA -carrier communities described that exposure to RRM-positive stories—particularly from peers who had already undergone RRM—helped reframe the surgery as acceptable, achievable, and even expected. In a support group evaluation study by Bertonazzi et al.,[ 37 ] many carriers explicitly stated that hearing others’ experiences ‘helped [them] decide to do a double mastectomy’. Similarly, Dibble et al., [ 38 ] found that online support-group engagement provided emotional validation and decisional reinforcement, with RRM-positive discussions lowering psychological resistance and promoting surgery as a normative step for high-risk women. These findings were also outlined by Gaba et al., [ 39 ] who reported that pre-menopausal BRCA PV carriers frequently relied on online BRCA forums, where posts from women satisfied with RRM created a strong social endorsement effect. Morgan and coworkers [ 22 ] further demonstrated that support-group use was significantly more common among women who chose RRM than among those who opted for surveillance, highlighting that peer-network engagement is not merely descriptive but selectively clustered around women inclined toward surgery. Together, these studies support the interpretation that peer narratives—both digital and in-person—can normalize, encourage, and emotionally support the decision to pursue RRM. In our cohort, the influence of family physicians and religious leaders on RRM uptake was uniformly minimal. This pattern is highly consistent with contemporary evidence from other similarly focused studies. Segerer et al., [ 13 ] found no independent association between cultural or religious background and the choice of risk reducing surgery among BRCA carriers. Similarly, Puski et al., [ 40 ] demonstrated that BRCA carriers overwhelmingly identified genetics specialists and close family members—rather than primary-care or other non-specialist clinicians—as the meaningful influencers in risk-management decisions. Qualitative research further supports these findings: Graham et al., [ 41 ] showed that women perceive RRM as a personally owned, self-directed act of controlling hereditary cancer risk, with health professionals operating primarily as information providers rather than decisional authorities. Hesse-Biber and An [ 42 ] likewise reported that women’s post-testing decisions are shaped predominantly by personal risk perceptions, family cancer narratives, and social-network experiences, with minimal impact from spiritual leaders or non-specialist clinicians. From a familial-cancer perspective, our findings underscore that decisions regarding RRM are embedded within lived family cancer narratives rather than being driven primarily by formal medical authority. This observation reinforces the importance of incorporating family history context, peer support exposure, and cancer-related worry into genetic counselling frameworks for BRCA carriers. While the current study combined with previous research that focused on RRM Vs. non-surgical options provide some insights, several gaps need to be addressed to facilitate future studies: focus only on cancer free BRCA carriers (exclude those who were already diagnosed with BC electing for contralateral risk reducing mastectomy); a longitudinal, multiple time contact points, prospective study is urgently needed; expand such RRM decision affecting factors studies to culturally divergent populations; unified, validated RRM focused questionnaires with identical parameters collected to enable a more precise comparison between diverse populations; deeper qualitative and mixed-methods research may help elucidate the variety of psychological, body-image, partner/family influence, decisional conflict and regret over time. In this context, although the cohort reported herein was NGO-based, uptake rates and decision patterns were comparable to those reported in population-based European cohorts, supporting external validity. In conclusion, our data reinforces a multifactorial model of RRM decision-making: one in which perceived risk, lived family experience, emotional burden, and support networks are more important in RRM decision than external authority non professional figures. Future prospective studies in ethnically diverse populations are needed to implement these results in order to improve genetic counselling, individualized risk communication, and patient-centered decision-support tools. Declarations Acknowledgements The authors thank all Good Genes NGO members for their participation in this study. Funding statement This research received no specific grant from any funding agency in the public, commercial, or not‑for‑profit sectors.” Author contributions KA, LM and EF conceived and designed the study. KA, TS and LM coordinated data collection and participant recruitment. YL and EF performed the statistical analyses and interpreted the data. YL drafted the first version of the manuscript. KA, TS, LM and EF critically reviewed and revised the manuscript for important intellectual content. All authors read and approved the final manuscript.” Conflict of interest / Competing interests The authors declare that they have no conflicts of interest. Ethics approval and consent The study was approved by the local ethics committee (SMC 1492-14), and all participants consented for participation prior to completing the questionnaire, as implied by consent completion, in compliance with the IRB approved protocol. Data availability De-identified data that support the findings of this study are available from the corresponding author upon reasonable request. References Kuchenbaecker KB, Hopper JL, Barnes DR, Phillips KA, Mooij TM, Roos-Blom MJ et al (2017) Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers. JAMA 317(23):2402–2416 Katsika L, Boureka E, Kalogiannidis I, Tsakiridis I, Tirodimos I, Lallas K, Tsimtsiou Z, Dagklis T (2024) Screening for Breast Cancer: A Comparative Review of Guidelines. Life (Basel) 14(6):777. 10.3390/life14060777 NCCN guidelines - https://www.nccn.org/professionals/physician_gls/pdf/breast-screening.pdf Sessa C, Balmaña J, de Azambuja E, Sonke GS, Paluch-Shimon S, Cardoso F et al (2023) Risk reduction and screening of cancer in hereditary breast–ovarian cancer syndromes: ESMO clinical practice guideline. Ann Oncol 34(1):33–47. 10.1016/j.annonc.2022.10.004 https:// -detail?category=2&id=1545&utm_source Gaba F, Piek J, Manchanda R, Dyer R, Smrkolj Š, Sarid Mogilevsky S et al (2023) Breast cancer risk and breast-cancer-specific mortality following risk-reducing salpingo-oophorectomy in BRCA carriers: A systematic review and meta-analysis. Cancers (Basel) 15(5):1625. 10.3390/cancers15051625 Metcalfe K, Eisen A, Senter L, Armel S, Bordeleau L, Meschino WS et al (2019) International trends in the uptake of cancer risk reduction strategies in women with a BRCA1 or BRCA2 mutation. Br J Cancer 121(1):15–21 Willert CB, Mellemkjær L, Tolver A, Gerdes A-MA, Rosthøj S, Wadt K et al (2025) Time trends, uptake, and oncological effects of risk-reducing surgeries in 3067 Danish BRCA1/2 carriers: a population-based study with matched controls. Breast Cancer Res Treat. [Epub ahead of print] 10.1007/s10549-025-07821-4 Hyldebrandt HK, Stormorken AT, Vitelli V, Mæhle L, Schlichting E, Grindedal EM (2025) Risk reducing mastectomy in Norwegian BRCA1/2 carriers. Eur J Surg Oncol 51(3):109571. 10.1016/j.ejso.2024.109571 Evans DGR, Howell A, Ward D, Prestwich F, Betterton J, Duffy SW et al (2021) Twenty-year experience of breast-cancer risk management in the U.K. familial-risk program. J Med Genet 58(5):329–336. 10.1136/jmedgenet-2020-107387 Zimovjanova M, Skapa P, Fedorova L, Horak J, Brandejsova J, Foretova L (2023) Uptake and effectiveness of risk-reducing surgeries in unaffected female BRCA1 and BRCA2 carriers: A single institution experience in the Czech Republic. Cancers (Basel) 15(4):1072. 10.3390/cancers15041072 Simões Corrêa Galendi JS, Kautz-Freimuth S, Stock S, Müller D (2022) Uptake rates of risk-reducing surgeries for women at increased risk of hereditary breast and ovarian cancer applied to cost-effectiveness analyses: a scoping systematic review. Cancers (Basel) 14(7):1786. 10.3390/cancers14071786 Segerer R, Steinke-Lange V, Kurz C, Dworniczak B, Rahner N, Hinterberger-Fischer M et al (2020) Factors impacting on decision-making towards prophylactic surgeries in BRCA mutation carriers and women with familial predisposition. Breast Care (Basel) 15(3):253–259. 10.1159/000503370 Park S, Kim Y, Kim S (2020) Factors associated with the decision to undergo risk-reducing salpingo-oophorectomy among women at high risk for hereditary breast and ovarian cancer: a systematic review. Korean J Women Health Nurs 26(4):285–299. 10.4069/kjwhn.2020.11.19 Isselhard A, Niels T, Antoniadis A, Becker K, Kohls E, Nothacker J et al (2023) Psychological distress and decision-making factors for prophylactic bilateral mastectomy in cancer-unaffected BRCA1/2 pathogenic variant carriers. Psychooncology 32(4):640–648. 10.1002/pon.6111 Chavarri-Guerra Y, Villarreal-Garza C, Lazcano-Ponce E, Banegas MP, Flores-Luna L, Komenaka I et al (2024) Uptake of risk-reducing surgeries in an international real-world cohort of Hispanic women. JCO Glob Oncol 10:e2400097. 10.1200/GO.24.00097.​ McGarrigle SA, Prizeman G, Spillane C, Byrne N, Drury A et al (2024) Decision aids for female BRCA mutation carriers: a scoping review. BMJ Open 14(6):e076876. 10.1136/bmjopen-2023-076876 Laitman Y, Feng B, Zamir IM, Levi R, Friedman E, Kaufman B et al (2014) Rates of risk-reducing surgery in Israeli BRCA1 and BRCA2 mutation carriers. Clin Genet 85(1):68–71. 10.1111/cge.12149 Kram V, Peretz T, Sagi M, Levy-Lahad E, Friedman E (2006) Acceptance of preventive surgeries by Israeli women who had undergone BRCA testing. Fam Cancer 5(4):327–335. 10.1007/s10689-006-0002-z Nahshon C, Segev Y, Schmidt M, Lavie O (2024) Attitude of BRCA1/2 mutation carriers towards surgical risk reduction for breast, ovarian and uterine cancer: still much to be done. Int J Gynecol Cancer 34(2):260–266. 10.1136/ijgc-2023-004801 Mesa-Chavez F, Chavarri-Guerra Y, Aguilar-Y-Mendez D, Becerril-Gaitan A, Vaca-Cartagena BF, Carrillo-Bedoya A et al (2024) Uptake of Risk-Reducing Measures, Cascade Testing, and Related Challenges Among Carriers of Breast Cancer-Associated Germline Pathogenic Variants in Mexico. JCO Glob Oncol 10:e2300417. 10.1200/GO.23.00417 Morgan J, Lugg-Widger F, Rylance A, Rice C, Lewis K, Edwards A et al (2024) Psychosocial outcomes after varying risk management strategies in women at increased familial breast cancer risk: A mixed methods study of patient and partner outcomes. Ann R Coll Surg Engl 106(1):78–91. 10.1308/rcsann.2023.0042 Modaffari P, Ponzone R, Ferrari A, Cipullo I, Liberale V, D'Alonzo M, Maggiorotto F, Biglia N (2019) Concerns and Expectations of Risk-Reducing Surgery in Women with Hereditary Breast and Ovarian Cancer Syndrome. J Clin Med 8(3):313. 10.3390/jcm8030313 Mann HB, Whitney DR (1947) On a test of whether one of two random variables is stochastically larger than the other. Ann Math Stat 18(1):50–60 Hochberg Y, Benjamini Y (1990) More powerful procedures for multiple significance testing. Stat Med 9(7):811–818. 10.1002/sim.4780090710 Norman G (2010) Likert scales, levels of measurement and the laws of statistics. Adv Health Sci Educ 15(5):625–632 Akoglu H (2018) User's guide to correlation coefficients. Turk J Emerg Med 18(3):91–93. 10.1016/j.tjem.2018.08.001 Dick J, Ablasser G, Ehlers M, Steinemann N, Schulze S, Preisler-Adams S et al (2022) Psychological factors and the uptake of preventative measures in BRCA1/2 pathogenic variant carriers: Results of a prospective cohort study. Hered Cancer Clin Pract 20(1):38. 10.1186/s13053-022-00244-y Portnoy DB, Loud JT, Han PKJ, Mai PL, Greene MH (2015) Effects of false-positive cancer screenings and cancer worry on risk-reducing surgery among BRCA1/2 mutation carriers. Health Psychol 34(7):709–717. 10.1037/hea0000156 Padamsee TJ, Wills CE, Yee LD, Paskett ED (2017) Decision making for breast cancer prevention among women at elevated risk. Breast Cancer Res 19(1):34. 10.1186/s13058-017-0826-5 Gilbert E, Zabor EC, Stempel M, Mangino DA, Kellick MG, Morrow M et al (2017) Differences among a modern cohort of BRCA mutation carriers choosing bilateral prophylactic mastectomies compared to breast surveillance. Ann Surg Oncol 24(10):3048–3054. 10.1245/s10434-017-5976-2 Singh K, Lester J, Karlan B, Bresee C, Geva T, Gordon O (2013) Impact of family history on choosing risk-reducing surgery among BRCA mutation carriers. Am J Obstet Gynecol 208(4):329. .e1-6 Dean M (2016) It’s not if I get cancer, it’s when I get cancer: BRCA-positive patients’ (un)certain health experiences regarding hereditary breast and ovarian cancer risk. Soc Sci Med 163:21–27. 10.1016/j.socscimed.2016.06.039 Dean M, Fisher CL (2019) Uncertainty and previvors’ cancer risk management: understanding the decision-making process. J Appl Commun Res 47(4). 10.1080/00909882.2019.1657236 Hoskins LM, Greene MH (2012) Anticipatory loss and early mastectomy for young female BRCA1/2 mutation carriers. Qual Health Res 22(12):1633–1646. 10.1177/1049732312458182 Torrisi C, Wareg NK, Brandt Anbari A (2024) Decision-making for bilateral risk-reducing mastectomy for an increased lifetime breast cancer risk: a qualitative metasynthesis. Psychooncology 33(3):e6311. 10.1002/pon.6311 Bertonazzi B, Bellati F, Ricciardi E, Capriglione S, Perrone E, Di Meglio A et al (2022) Outcomes of support groups for carriers of BRCA1/2. Fam Cancer 21(1):51–61 Dibble KE, Donorfio LKM, Britner PA, Bellizzi KM (2022) Perceptions and care Recommendations from Previvors: Qualitative analysis of female BRCA1/2 mutation Carriers' experience with genetic testing and counseling. Gynecol Oncol Rep 41:100989. 10.1016/j.gore.2022.100989 Gaba F, Manchanda R, Smrkolj S, Sarid Mogilevsky S, Seckl MJ, McCluggage WG et al (2021) Surgical decision-making in premenopausal BRCA carriers: The influence of online support forums. Breast J 27(2):179–188 Puski A, Hovick S, Senter L, Toland AE (2018) Involvement and Influence of Healthcare Providers, Family Members, and Other Mutation Carriers in the Cancer Risk Management Decision-Making Process of BRCA1 and BRCA2 Mutation Carriers. J Genet Couns 27(5):1291–1301. 10.1007/s10897-018-0254-4 Graham R, Owens M, Priest H, Hutton S (2018) Constructions of Decision Making for Risk-Reducing Mastectomy. Qual Health Res 28(10):1595–1609. 10.1177/1049732318785372 Hesse-Biber S, An C (2016) Genetic testing and post-testing decision making among BRCA-positive mutation women: A psychosocial approach. J Genet Couns 25(5):978–992. 10.1007/s10897-015-9929-2 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 23 Apr, 2026 Reviews received at journal 23 Mar, 2026 Reviewers agreed at journal 23 Mar, 2026 Reviewers agreed at journal 10 Mar, 2026 Reviewers agreed at journal 05 Feb, 2026 Reviewers agreed at journal 03 Feb, 2026 Reviewers invited by journal 21 Jan, 2026 Editor assigned by journal 13 Jan, 2026 Submission checks completed at journal 13 Jan, 2026 First submitted to journal 05 Jan, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {\"props\":{\"pageProps\":{\"initialData\":{\"identity\":\"rs-8523281\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":false,\"archivedVersions\":[],\"articleType\":\"Research Article\",\"associatedPublications\":[],\"authors\":[{\"id\":578133346,\"identity\":\"b86a0130-89d5-4826-8424-8c4af7a178a5\",\"order_by\":0,\"name\":\"Yael Laitman\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Assuta Medical Center\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Yael\",\"middleName\":\"\",\"lastName\":\"Laitman\",\"suffix\":\"\"},{\"id\":578133359,\"identity\":\"00eeee68-3b54-4bd7-8c05-2ff2a67a633b\",\"order_by\":1,\"name\":\"Karin Aharon\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Good Genes NGO\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Karin\",\"middleName\":\"\",\"lastName\":\"Aharon\",\"suffix\":\"\"},{\"id\":578133363,\"identity\":\"d4263bc2-7cca-47da-a5ba-7cb3aa9dd400\",\"order_by\":2,\"name\":\"Talia Schloss\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Good Genes NGO\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Talia\",\"middleName\":\"\",\"lastName\":\"Schloss\",\"suffix\":\"\"},{\"id\":578133367,\"identity\":\"66decf2b-2852-44bf-8e46-467172e4627c\",\"order_by\":3,\"name\":\"Libby Margolin\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Good Genes NGO\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Libby\",\"middleName\":\"\",\"lastName\":\"Margolin\",\"suffix\":\"\"},{\"id\":578133368,\"identity\":\"d7bb8c91-65d2-4f9f-8258-ee6a724b85b1\",\"order_by\":4,\"name\":\"Eitan Friedman\",\"email\":\"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA9ElEQVRIiWNgGAWjYBAC9gbGBiBlgyacUIBbC88BxkagnjQJqFKYFgN8WhhA1hxG08KATwt7c/uDnzvO1/HPSD4mwfjDLrGB/fADhgf4tPAcbGzsPXNbQuJGWrIBQ0JyYgNPmgFeh9lLJDY28LbdlmC4kWP4gCGBObGBIYeAX+QfNjb+bTsnIX8j/8MBhoT6xAb+NwS0SDA2NvO2HZAwuJHDCLTlcGKDBCFbeBIbZ8u2JUtuPPPM2CAh7bhxm8QzgwN4tbAff/DxbZsdv9zx5GcSH2yqZfv5kx8+/FGBWwsqSABiNiA+QKyGUTAKRsEoGAXYAQDnk09dOjmuKAAAAABJRU5ErkJggg==\",\"orcid\":\"\",\"institution\":\"Tel Aviv University\",\"correspondingAuthor\":true,\"prefix\":\"\",\"firstName\":\"Eitan\",\"middleName\":\"\",\"lastName\":\"Friedman\",\"suffix\":\"\"}],\"badges\":[],\"createdAt\":\"2026-01-05 16:09:51\",\"currentVersionCode\":1,\"declarations\":\"\",\"doi\":\"10.21203/rs.3.rs-8523281/v1\",\"doiUrl\":\"https://doi.org/10.21203/rs.3.rs-8523281/v1\",\"draftVersion\":[],\"editorialEvents\":[],\"editorialNote\":\"\",\"failedWorkflow\":false,\"files\":[{\"id\":100972914,\"identity\":\"6f165c4b-ceee-4430-8c90-b08ed7f391c0\",\"added_by\":\"auto\",\"created_at\":\"2026-01-23 10:27:45\",\"extension\":\"docx\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"acdc-reference\",\"size\":98149,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"RRMGOODGENESFamilialCancerfINAL012026.docx\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-8523281/v1/bcd926874ff101f9c5c8aade.docx\"},{\"id\":100972847,\"identity\":\"cf9a91bd-6dc9-443b-84dc-51c1204d8d0b\",\"added_by\":\"auto\",\"created_at\":\"2026-01-23 10:27:31\",\"extension\":\"json\",\"order_by\":1,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"acdc-reference\",\"size\":6845,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"33383b938650420aa10f39e5ea2289ba.json\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-8523281/v1/e2bf30e1ad948457eae2478a.json\"},{\"id\":100972890,\"identity\":\"dbd722f6-b476-4aa2-896a-eb4804bc9cc1\",\"added_by\":\"auto\",\"created_at\":\"2026-01-23 10:27:34\",\"extension\":\"xml\",\"order_by\":2,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"acdc-reference\",\"size\":116996,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"33383b938650420aa10f39e5ea2289ba1enriched.xml\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-8523281/v1/0e359f128c53b40dace4f9d8.xml\"},{\"id\":100972898,\"identity\":\"871ae8f8-6608-4e8a-a6fd-109f88b2dfe7\",\"added_by\":\"auto\",\"created_at\":\"2026-01-23 10:27:35\",\"extension\":\"png\",\"order_by\":4,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"acdc-reference\",\"size\":115449,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"Onlinefloatimage1.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-8523281/v1/469bb3877e6c14cf724d3100.png\"},{\"id\":100972913,\"identity\":\"2446611a-0820-44cf-b628-3ee4cd95fc8f\",\"added_by\":\"auto\",\"created_at\":\"2026-01-23 10:27:43\",\"extension\":\"xml\",\"order_by\":5,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"acdc-reference\",\"size\":113302,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"33383b938650420aa10f39e5ea2289ba1structuring.xml\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-8523281/v1/62c6577409305ff11c41ea93.xml\"},{\"id\":100972838,\"identity\":\"531ee658-16f8-4f77-866a-4841cbe87da7\",\"added_by\":\"auto\",\"created_at\":\"2026-01-23 10:27:27\",\"extension\":\"html\",\"order_by\":6,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"acdc-reference\",\"size\":127728,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"earlyproof.html\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-8523281/v1/c050969892a4c8e4dc652e61.html\"},{\"id\":100972896,\"identity\":\"3a8af1fb-40fe-4655-be8f-3db043f18618\",\"added_by\":\"auto\",\"created_at\":\"2026-01-23 10:27:35\",\"extension\":\"jpeg\",\"order_by\":1,\"title\":\"Figure 1\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":286180,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003ePredicted probability of RRM by age at \\u003cem\\u003eBRCA\\u003c/em\\u003e carrier diagnosis and early-onset family history among \\u003cem\\u003eBRCA1\\u003c/em\\u003e carriers. Curves represent model-based predicted probabilities of undergoing RRM (y‑axis) across age at \\u003cem\\u003eBRCA\\u003c/em\\u003ecarrier diagnosis (x‑axis). The solid black line represents women with no FDR with BC diagnosed before age 45. The dashed black line represents women with at least one FDR with BC diagnosed before age 45. The grey shaded area highlights the absolute difference in predicted probability of RRM between those with and without early-onset BC in FDRs at each age.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"floatimage1.jpeg\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-8523281/v1/63350e30b4688611eae9493f.jpeg\"},{\"id\":100972916,\"identity\":\"24da7510-3057-49a5-9863-39b4cb9b77c4\",\"added_by\":\"auto\",\"created_at\":\"2026-01-23 10:27:53\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":939318,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-8523281/v1/da81574e-44fc-43c8-9f00-cd14d48d571d.pdf\"}],\"financialInterests\":\"No competing interests reported.\",\"formattedTitle\":\"Factors influencing uptake of risk-reducing mastectomy among unaffected Israeli BRCA1/BRCA2 pathogenic variant carriers\",\"fulltext\":[{\"header\":\"Introduction\",\"content\":\"\\u003cp\\u003eWomen harboring pathogenic variants (PVs) in the \\u003cem\\u003eBRCA1\\u003c/em\\u003e or \\u003cem\\u003eBRCA2\\u003c/em\\u003e genes (=\\u0026thinsp;\\u003cem\\u003eBRCA\\u003c/em\\u003e) are at a substantially high lifetime risks for developing breast (BC) and ovarian cancer (OvC): for BC these risks are 69\\u0026ndash;72% and for OvC 17\\u0026ndash;44% by age 80 years [\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e]. Female \\u003cem\\u003eBRCA\\u003c/em\\u003e carriers are offered an intensified early surveillance scheme aimed at early detection of BC starting at age 25\\u0026ndash;30 years that include biannual clinical breast exam and breast imaging (MRI alternating with mammograms) [\\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e]. For active BC/ OvC risk reduction the only options are risk reducing surgeries \\u0026ndash; mastectomy (RRM) and salpingo-oophorectomy (RRSO) [\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e]. RRM has been shown to reduce BC incidence by up to 90\\u0026ndash;95% in \\u003cem\\u003eBRCA\\u003c/em\\u003e PV carriers [\\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e]. Thus, RRM is an option that should be discussed during oncogenetic counselling of cancer-free carriers. However, the decision to undergo RRM is complex, irreversible, and involves trade-offs including surgical risks, psychosocial and body‐image consequences, and implications for breast feeding or childbearing timing, especially among young women. Despite the proven effect of RRM on active BC risk reduction, uptake of RRM among unaffected \\u003cem\\u003eBRCA\\u003c/em\\u003e carriers appears to vary widely across countries and over time. Country-level analyses of more than 6,000 \\u003cem\\u003eBRCA\\u003c/em\\u003e carriers demonstrated striking international heterogeneity in the uptake of RRM. In the multinational study by Metcalfe et al. [\\u003cspan citationid=\\\"CR7\\\" class=\\\"CitationRef\\\"\\u003e7\\u003c/span\\u003e], RRM was chosen by 49.9% of U.S. carriers, approximately 40% of U.K. carriers, and only 4.5% of Polish carriers, representing the lowest rate among the ten participating countries. Comparable figures have been reported in large national cohorts: the Danish population-based registry of 3,067 \\u003cem\\u003eBRCA\\u003c/em\\u003e PV carriers showed 45\\u0026ndash;55% uptake of RRM [\\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e], with similar rates reported by a Norwegian national series [\\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e]. UK prospective data from Evans et al. [\\u003cspan citationid=\\\"CR10\\\" class=\\\"CitationRef\\\"\\u003e10\\u003c/span\\u003e] confirmed a 47.7% twenty-year uptake of RRM in \\u003cem\\u003eBRCA\\u003c/em\\u003e carriers. A Czech Republic retrospective cohort [\\u003cspan citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e] of 496 healthy \\u003cem\\u003eBRCA\\u003c/em\\u003e PV carriers from a surveillance program (2000\\u0026ndash;2020) found RRM uptake of ~\\u0026thinsp;31.5% with a significant increase after 2013 (12% in 2005\\u0026ndash;12 vs 31.6% in 2013\\u0026ndash;20). A recent review of 58 studies involving more than 30,000 high-risk women also confirmed wide inter-country variation [\\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e].\\u003c/p\\u003e \\u003cp\\u003eFactors affecting the decision to undergo RRM have been reported to include a wide range of variables: reproductive issues, psychosocial parameters, number of previous breast biopsies, family cancer history and age at cancer diagnosis in relatives, medical and genetic counselling involvement, spouse and family support, and system-level factors (e.g., physician guidance, availability of breast reconstruction, insurance coverage of the procedure) [\\u003cspan citationid=\\\"CR7\\\" class=\\\"CitationRef\\\"\\u003e7\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e, \\u003cspan additionalcitationids=\\\"CR14 CR15 CR16\\\" citationid=\\\"CR13\\\" class=\\\"CitationRef\\\"\\u003e13\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR17\\\" class=\\\"CitationRef\\\"\\u003e17\\u003c/span\\u003e]. Understanding why unaffected carriers elect or decline RRM is essential for optimizing genetic counselling, patient-centered risk communication, and shared decision-making.\\u003c/p\\u003e \\u003cp\\u003eSpecifically in Israel, data on RRM uptake and the factors that guide this decision are sparse. A questionnaire-based, single high-risk clinic study conducted by Laitman et al [\\u003cspan citationid=\\\"CR18\\\" class=\\\"CitationRef\\\"\\u003e18\\u003c/span\\u003e] among 170 cancer-free \\u003cem\\u003eBRCA\\u003c/em\\u003e PV carriers reported RRM uptake of 13% (22/170) at follow-up \\u0026ge;\\u0026thinsp;18 months. A prior Israeli survey (2004\\u0026ndash;06) of 99 women (43% carriers) reported\\u0026thinsp;~\\u0026thinsp;19% of carriers underwent RRM, and ~\\u0026thinsp;25% had positively considered it [\\u003cspan citationid=\\\"CR19\\\" class=\\\"CitationRef\\\"\\u003e19\\u003c/span\\u003e]. In this manuscript we explored the factors affecting the decision to undergo RRM in cancer free Israeli \\u003cem\\u003eBRCA\\u003c/em\\u003e PV carriers using a questionnaire-based data collection scheme.\\u003c/p\\u003e\"},{\"header\":\"Methods\",\"content\":\"\\u003cp\\u003e\\u003cb\\u003eParticipants-\\u003c/b\\u003e Israeli women who were all \\u003cem\\u003eBRCA\\u003c/em\\u003e PV carriers and members of the Good Genes nonprofit organization (\\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003ehttps://goodbrcagenes.org/\\u003c/span\\u003e\\u003cspan address=\\\"https://goodbrcagenes.org/\\\" targettype=\\\"URL\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e) were eligible for participation. The Good Genes NGO includes carriers from diverse geographic, religious, and socioeconomic backgrounds across Israel, mitigating concerns regarding single-clinic referral bias. After an initial notification of the objectives of the study and explaining the de-identified manner of data collection and analysis, a request for consent to participate was made and obtained. Each consenting participant was sent the questionnaire and returned the filled questionnaire via a secure link. The study protocol was approved by the local Ethics committee (SMC 1492-14).\\u003c/p\\u003e \\u003cp\\u003e \\u003cb\\u003eInstrument-\\u003c/b\\u003e Participants completed a structured questionnaire designed to assess factors influencing decisions regarding RRM in \\u003cem\\u003eBRCA\\u003c/em\\u003e PV carriers. The questionnaire integrated validated domains from prior surveys addressing attitudes toward surgical risk-reduction and preventive strategies in hereditary breast\\u0026ndash;ovarian cancer syndromes [e.g., 9, 20, 21]. The parameters evaluated included: age at genotyping, mutated gene, reason for genotyping, personal and family cancer history, reproductive variables, perceived cancer risk, body-image concerns, and psychological distress [\\u003cspan citationid=\\\"CR15\\\" class=\\\"CitationRef\\\"\\u003e15\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR22\\\" class=\\\"CitationRef\\\"\\u003e22\\u003c/span\\u003e]. Additional items explored were information sources, cultural and familial influences, medical professionals\\u0026rsquo; recommendations, and religious beliefs and practices [\\u003cspan citationid=\\\"CR14\\\" class=\\\"CitationRef\\\"\\u003e14\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR23\\\" class=\\\"CitationRef\\\"\\u003e23\\u003c/span\\u003e]. Responses were recorded using 5-point Likert scales (1 = \\u0026ldquo;strongly disagree\\u0026rdquo; to 5 = \\u0026ldquo;strongly agree\\u0026rdquo;) with free-text fields for qualitative insights. The questionnaire was pilot tested in a subset of 25 carriers for clarity and internal consistency before dissemination to the full cohort.\\u003c/p\\u003e \\u003cdiv id=\\\"Sec3\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eStatistical methods\\u003c/h2\\u003e \\u003cp\\u003eAnalyses were restricted to women with PVs in \\u003cem\\u003eBRCA1/BRCA2\\u003c/em\\u003e who were cancer-free at the time of management decision. The primary comparison was between women choosing RRM and those opting to be managed with surveillance. Age at \\u003cem\\u003eBRCA\\u003c/em\\u003e carrier diagnosis was treated as a continuous variable. Because age distributions were not assumed to be normal, we used the Mann\\u0026ndash;Whitney U test to compare age between RRM and surveillance groups [\\u003cspan citationid=\\\"CR24\\\" class=\\\"CitationRef\\\"\\u003e24\\u003c/span\\u003e]. Extreme outliers in age within the surveillance group were identified using the interquartile range (IQR) method (values\\u0026thinsp;\\u0026lt;\\u0026thinsp;Q1\\u0026thinsp;\\u0026minus;\\u0026thinsp;1.5\\u0026times;IQR or \\u0026gt;\\u0026thinsp;Q3\\u0026thinsp;+\\u0026thinsp;1.5\\u0026times;IQR) and excluded for age-specific descriptive statistics and the age comparison.\\u003c/p\\u003e \\u003cp\\u003eFamily history variables were summarized as both binary indicators (any affected first- or second-degree relative; any first-degree relative with BC or OvC; any first-degree relative with BC\\u0026thinsp;\\u0026lt;\\u0026thinsp;45 years) and counts of affected relatives. Between-group differences in binary family history variables were evaluated using Pearson\\u0026rsquo;s chi-square tests. For count variables (number of affected first- or second-degree relatives), we reported means, standard deviations, and medians by management group; where formal comparisons were performed, non-parametric tests were preferred given skewed distributions. To account for multiple comparisons across family history variables, p-values from univariate tests were adjusted using the Benjamini\\u0026ndash;Hochberg false discovery rate (FDR) procedure, and we report both raw p-values and FDR-adjusted q-values [\\u003cspan citationid=\\\"CR25\\\" class=\\\"CitationRef\\\"\\u003e25\\u003c/span\\u003e]. All tests were two-sided, and statistical significance was a priori defined as q\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.05. Analyses were additionally stratified by gene (\\u003cem\\u003eBRCA1\\u003c/em\\u003e vs \\u003cem\\u003eBRCA2\\u003c/em\\u003e) to explore whether patterns of age and family history differed by genotype.\\u003c/p\\u003e \\u003cp\\u003eWe used multivariable logistic regression to estimate adjusted odds ratios for undergoing RRM Vs. surveillance, including age at \\u003cem\\u003eBRCA\\u003c/em\\u003e carrier diagnosis, \\u003cem\\u003eBRCA1\\u003c/em\\u003e versus \\u003cem\\u003eBRCA2\\u003c/em\\u003e status, and the presence of at least one first-degree relative with BC diagnosed before age 45 years as predictors. Odds ratios were obtained by exponentiating the logistic regression coefficients, providing adjusted effect estimates for each predictor on the likelihood of choosing RRM.\\u003c/p\\u003e \\u003cp\\u003eParticipants rated the influence of multiple decision-related factors on a 1\\u0026ndash;5 Likert scale (1\\u0026thinsp;=\\u0026thinsp;not at all important, 5\\u0026thinsp;=\\u0026thinsp;extremely important) [\\u003cspan citationid=\\\"CR26\\\" class=\\\"CitationRef\\\"\\u003e26\\u003c/span\\u003e], when choosing between RRM and continued surveillance. Items were grouped conceptually into five domains: (1) risk-perception factors (e.g. active BC risk reduction, fear of developing cancer, family history), (2) family-oriented factors (e.g. worrying about the children, not wanting to become a burden on the family), (3) treatment-burden/side-effect concerns (e.g. fear of surgical complications, fear of recovery from surgery, reducing the need for frequent surveillance, preventing frequent biopsies, worry about body image), (4) information-source factors (e.g. information from clinical teams, general internet sources, support group), and (5) religious/spiritual factors (e.g. personal religious beliefs, guidance from a spiritual leader - a rabbi). For each item, we calculated the mean and standard deviation; we then computed domain-level averages to compare the relative influence of these broader constructs.\\u003c/p\\u003e \\u003c/div\\u003e\"},{\"header\":\"Results\",\"content\":\"\\u003cp\\u003eA total of 512 single \\u003cem\\u003eBRCA\\u003c/em\\u003e PV carriers agreed to participate and filled the questionnaire: 308 (60%) were \\u003cem\\u003eBRCA1\\u003c/em\\u003e PV carriers and 204 (40%)\\u0026ndash; \\u003cem\\u003eBRCA2\\u003c/em\\u003e PV carriers. Mean age (\\u003cspan type=\\\"Underline\\\" class=\\\"Underline\\\" name=\\\"Emphasis\\\"\\u003e\\u0026plusmn;\\u003c/span\\u003e\\u0026thinsp;SD) at data collection was 45.5\\u0026thinsp;\\u003cspan type=\\\"Underline\\\" class=\\\"Underline\\\" name=\\\"Emphasis\\\"\\u003e\\u0026plusmn;\\u003c/span\\u003e\\u0026thinsp;10.8 years (range 29\\u0026ndash;77; median 44 years) and mean\\u0026thinsp;\\u003cspan type=\\\"Underline\\\" class=\\\"Underline\\\" name=\\\"Emphasis\\\"\\u003e\\u0026plusmn;\\u003c/span\\u003e\\u0026thinsp;SD at genotyping and \\u003cem\\u003eBRCA\\u003c/em\\u003e carriership disclosure 37.9\\u0026thinsp;\\u003cspan type=\\\"Underline\\\" class=\\\"Underline\\\" name=\\\"Emphasis\\\"\\u003e\\u0026plusmn;\\u003c/span\\u003e\\u0026thinsp;10.6 (range 25\\u0026ndash;70; median 37 years). Of participants, 121 were diagnosed with cancer \\u0026ndash; 102 (84.3%) with BC. Mean age at BC diagnosis 43.5\\u0026thinsp;\\u003cspan type=\\\"Underline\\\" class=\\\"Underline\\\" name=\\\"Emphasis\\\"\\u003e\\u0026plusmn;\\u003c/span\\u003e\\u0026thinsp;11.3 years (range 24\\u0026ndash;68; median 41 years).\\u003c/p\\u003e \\u003cp\\u003eAmong cancer-free \\u003cem\\u003eBRCA\\u003c/em\\u003e PV carriers, 119 (30%) elected RRM and 272 (70%) chose surveillance. The mean time from genetic test results disclosure to actual RRM was 4.27\\u0026thinsp;\\u003cspan type=\\\"Underline\\\" class=\\\"Underline\\\" name=\\\"Emphasis\\\"\\u003e\\u0026plusmn;\\u003c/span\\u003e\\u0026thinsp;4.7 years (range 0\\u0026ndash;19; median 2 years). Women undergoing RRM were slightly older at \\u003cem\\u003eBRCA\\u003c/em\\u003e carrier diagnosis than those managed with surveillance (mean 37.6\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;8.7 vs 35.6\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;9.8 years; Mann\\u0026ndash;Whitney U p\\u0026thinsp;=\\u0026thinsp;0.017, q\\u0026thinsp;=\\u0026thinsp;0.259), after exclusion of age outliers in the surveillance group. Median age at \\u003cem\\u003eBRCA\\u003c/em\\u003e carrier diagnosis was slightly lower for \\u003cem\\u003eBRCA1\\u003c/em\\u003e PV carriers (32 years) than \\u003cem\\u003eBRCA2\\u003c/em\\u003e PV carriers (37 years) in the surveillance arm, but these differences were modest and did not translate into large shifts in the relative uptake of RRM versus surveillance by gene. Family history of BC and OvC was highly prevalent in both groups, with no statistically significant differences after multiple-testing correction: ~61% of women in both RRM and surveillance groups had at least one affected first-degree relative (FDR) with BC or OvC, and ~\\u0026thinsp;38% had an affected FDR with BC. The proportion with an affected FDR with BC before age 45 was numerically higher in the RRM group (about one in five) compared with surveillance, but the difference did not retain statistical significance after FDR correction (q\\u0026thinsp;\\u0026ge;\\u0026thinsp;0.05), although effect sizes were directionally consistent. Patterns for second-degree relatives (SDR) were similar, with overlapping distributions of the number of affected relatives in both management groups. When stratified by gene, \\u003cem\\u003eBRCA1\\u003c/em\\u003e and \\u003cem\\u003eBRCA2\\u003c/em\\u003e carriers showed broadly comparable family history profiles within each management strategy.\\u003c/p\\u003e \\u003cp\\u003eMultivariable logistic regression including age at \\u003cem\\u003eBRCA\\u003c/em\\u003e carrier diagnosis, mutated \\u003cem\\u003eBRCA\\u003c/em\\u003e gene, family history variables, global family history measure (any affected FDR, any affected SDR, or the number of affected relatives) was independently associated with undergoing RRM versus surveillance. However, the presence of at least one FDR with BC diagnosed\\u0026thinsp;\\u003cspan type=\\\"Underline\\\" class=\\\"Underline\\\" name=\\\"Emphasis\\\"\\u003e\\u0026le;\\u003c/span\\u003e\\u0026thinsp;45 years of age showed the largest effect size, with higher odds of choosing RRM compared with surveillance. Among \\u003cem\\u003eBRCA1\\u003c/em\\u003e PV carriers (n\\u0026thinsp;=\\u0026thinsp;218), approximately one-third (32%) underwent RRM. RRM uptake was strongly associated with early-onset family history: only about one-third (32%) of \\u003cem\\u003eBRCA1\\u003c/em\\u003e carriers with no FDR diagnosed with BC\\u0026thinsp;\\u0026lt;\\u0026thinsp;45 years chose RRM, compared with one-half (52%) of those with at least one FDR with BC diagnosed\\u0026thinsp;\\u0026lt;\\u0026thinsp;45 years of age. The corresponding logistic regression model showed higher predicted probabilities of RRM at younger ages and consistently higher probabilities across age for women with early-onset family history (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e).\\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003cp\\u003eAmong \\u003cem\\u003eBRCA2\\u003c/em\\u003e carriers (n\\u0026thinsp;=\\u0026thinsp;174), overall RRM uptake was slightly lower, at about one-quarter (26%). As in \\u003cem\\u003eBRCA1\\u003c/em\\u003e, early-onset family history was associated with more frequent RRM: only about 25% of \\u003cem\\u003eBRCA2\\u003c/em\\u003e PV carriers without an FDR with BC\\u0026thinsp;\\u0026lt;\\u0026thinsp;45 years underwent RRM, compared with approximately 47% of those with \\u0026ge;\\u0026thinsp;1 early-onset BC in FDR. The fitted model for \\u003cem\\u003eBRCA2\\u003c/em\\u003e showed the same directional pattern, with higher predicted probabilities of RRM for women with early-onset family history across the age range, although the absolute differences between groups were smaller than in \\u003cem\\u003eBRCA1\\u003c/em\\u003e PV carriers.\\u003c/p\\u003e \\u003cp\\u003eWomen opting for RRM had a different distribution of referral reasons \\u0026mdash; particularly more \\u0026ldquo;family history of cancer\\u0026rdquo; and less \\u0026ldquo;not recorded\\u0026rdquo; than the non-RRM group. This pattern strongly suggests that those choosing RRM were genotyped with clearer and more targeted indications. \\u003cem\\u003eBRCA1\\u003c/em\\u003e PV carriers were more likely to undergo RRM compared with \\u003cem\\u003eBRCA2\\u003c/em\\u003e PV carriers. This is clinically expected: \\u003cem\\u003eBRCA1\\u003c/em\\u003e is associated with higher and earlier BC risk. Women in the RRM group were more likely to have children than those in the non-RRM group. However, the level of effect (as determined by V Cramer) was small-moderate (0.124\\u0026ndash;0.216) [\\u003cspan citationid=\\\"CR27\\\" class=\\\"CitationRef\\\"\\u003e27\\u003c/span\\u003e], meaning that these differences had very limited clinical implications or significance. Marital status, level of religious beliefs and practices, and parental origin of the mutation, did not differ significantly between the RRM vs surveillance groups (Table\\u0026nbsp;\\u003cspan refid=\\\"Tab1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e).\\u003c/p\\u003e \\u003cp\\u003e \\u003cdiv class=\\\"gridtable\\\"\\u003e\\u003ctable float=\\\"Yes\\\" id=\\\"Tab1\\\" border=\\\"1\\\"\\u003e \\u003ccaption language=\\\"En\\\"\\u003e \\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 1\\u003c/div\\u003e \\u003cdiv class=\\\"CaptionContent\\\"\\u003e \\u003cp\\u003eComparison of relevant features in RRM Vs surveillance opting groups.\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/caption\\u003e \\u003ccolgroup cols=\\\"5\\\"\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c1\\\" colnum=\\\"1\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c2\\\" colnum=\\\"2\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c3\\\" colnum=\\\"3\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c4\\\" colnum=\\\"4\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c5\\\" colnum=\\\"5\\\"\\u003e\\u003c/div\\u003e \\u003cthead\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eVariable\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eRRM (n\\u0026thinsp;=\\u0026thinsp;119)\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003eNon-RRM (n\\u0026thinsp;=\\u0026thinsp;272)\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003ep-value\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003eCramer\\u0026rsquo;s V\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003c/thead\\u003e \\u003ctbody\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eAge at genotyping\\u003c/b\\u003e,\\u003c/p\\u003e \\u003cp\\u003e\\u003cb\\u003emean\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;SD (years)\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e37.6\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;8.7\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e35.6\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;9.8\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003e0.045\\u003c/b\\u003eᵃ\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e\\u0026mdash;\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eReason for genotyping\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003e0.0004\\u003c/b\\u003eᵇ\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003e0.216\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eScreening\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e24\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e54\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eMutation in family\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e42\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e129\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eFamily history of cancer\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e52\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e69\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eNot recorded\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e1\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e20\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eMarital status\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.505ᵇ\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.059\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eMarried\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e103\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e224\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eSeparated/divorced\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e8\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e28\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eSingle\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e8\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e20\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eOffspring\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003e0.0145\\u003c/b\\u003eᵇ\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003e0.124\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eYes\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e108\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e218\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eNo\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e11\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e54\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eReligious status\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.497ᵇ\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.060\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eOrthodox\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e3\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e9\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eConservative\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e18\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e53\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eSecular\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e99\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e210\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eMutated gene\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003e0.011\\u003c/b\\u003eᵇ\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003e0.128\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eBRCA1\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e78\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e139\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eBRCA2\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e41\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e133\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eParental origin of PV\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.313ᵇ\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.077\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eMaternal\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e51\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e97\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003ePaternal\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e55\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e134\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eUnknown\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e13\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e41\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e \\u003c/tr\\u003e \\u003c/tbody\\u003e \\u003c/colgroup\\u003e \\u003ctfoot\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"5\\\"\\u003e\\u003cb\\u003eFootnotes\\u003c/b\\u003e:\\u003c/td\\u003e\\u003c/tr\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"5\\\"\\u003eᵃ Welch\\u0026rsquo;s t-test.\\u003c/td\\u003e\\u003c/tr\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"5\\\"\\u003eᵇ χ\\u0026sup2; test of independence.\\u003c/td\\u003e\\u003c/tr\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"5\\\"\\u003eBold p-values indicate statistical significance at α\\u0026thinsp;=\\u0026thinsp;0.05.\\u003c/td\\u003e\\u003c/tr\\u003e \\u003c/tfoot\\u003e \\u003c/table\\u003e\\u003c/div\\u003e \\u003c/p\\u003e \\u003cp\\u003eDecision-related factors were rated on a 1\\u0026ndash;5 Likert scale, with higher scores indicating greater influence. When focusing on RRM, the most influential determinants were active BC risk reduction and fear of developing cancer, both with mean scores (4.96\\u0026thinsp;\\u003cspan type=\\\"Underline\\\" class=\\\"Underline\\\" name=\\\"Emphasis\\\"\\u003e\\u0026plusmn;\\u003c/span\\u003e\\u0026thinsp;0.23 and 4.86\\u0026thinsp;\\u003cspan type=\\\"Underline\\\" class=\\\"Underline\\\" name=\\\"Emphasis\\\"\\u003e\\u0026plusmn;\\u003c/span\\u003e\\u0026thinsp;0.50, respectively). Family-related motivations were also strong: \\u0026ldquo;worrying about my kids\\u0026rdquo; and \\u0026ldquo;not to become a burden on my family\\u0026rdquo; had means of 4.61\\u0026thinsp;\\u003cspan type=\\\"Underline\\\" class=\\\"Underline\\\" name=\\\"Emphasis\\\"\\u003e\\u0026plusmn;\\u003c/span\\u003e\\u0026thinsp;1.04 and 4.08\\u0026thinsp;\\u003cspan type=\\\"Underline\\\" class=\\\"Underline\\\" name=\\\"Emphasis\\\"\\u003e\\u0026plusmn;\\u003c/span\\u003e\\u0026thinsp;1.32, respectively, indicating that protecting children and avoiding future caregiving burden are major drivers of the choice for RRM. Additional pro-RRM factors with more than moderate influence included efforts to prevent frequent biopsies, and the wish to reduce the need for ongoing surveillance, (ranging between 3.75\\u0026ndash;3.77). Information from medical teams also contributed meaningfully, with average influence scores in the moderate-to-high range (3.67\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;1.25).\\u003c/p\\u003e \\u003cp\\u003eFactors that tended to support continued surveillance rather than RRM were weaker in magnitude. The most prominent surveillance-leaning factors were fear of surgical complications (3.77\\u0026thinsp;\\u003cspan type=\\\"Underline\\\" class=\\\"Underline\\\" name=\\\"Emphasis\\\"\\u003e\\u0026plusmn;\\u003c/span\\u003e\\u0026thinsp;1.3), fear of recovery from surgery (3.73\\u0026thinsp;\\u003cspan type=\\\"Underline\\\" class=\\\"Underline\\\" name=\\\"Emphasis\\\"\\u003e\\u0026plusmn;\\u003c/span\\u003e\\u0026thinsp;1.36), and worry about body image (3.50\\u0026thinsp;\\u003cspan type=\\\"Underline\\\" class=\\\"Underline\\\" name=\\\"Emphasis\\\"\\u003e\\u0026plusmn;\\u003c/span\\u003e\\u0026thinsp;1.39), all of which represent concerns about the immediate and long-term consequences of major surgery. Internet-based and social media information had moderate average influence (means around 3.3), but with large variability between women. The views of family and friends about surgery played a smaller, though non-negligible, role (mean\\u0026thinsp;\\u0026asymp;\\u0026thinsp;2.4). Religious beliefs and guidance from a spiritual leader (rabbi) showed consistently low mean scores (around 1.2). Overall, domain-level analyses show that risk perception and family-oriented motivations dominate the decision landscape, with treatment-burden concerns and information sources exerting moderate influence and religious/spiritual considerations contributing little on average.\\u003c/p\\u003e \\u003cp\\u003eNotably, women opting for RRM would make the same decision (4.76\\u0026thinsp;\\u003cspan type=\\\"Underline\\\" class=\\\"Underline\\\" name=\\\"Emphasis\\\"\\u003e\\u0026plusmn;\\u003c/span\\u003e\\u0026thinsp;0.65), and would recommend other \\u003cem\\u003eBRCA\\u003c/em\\u003e PV carriers to undergo the same risk reducing surgery (4.55\\u0026thinsp;\\u003cspan type=\\\"Underline\\\" class=\\\"Underline\\\" name=\\\"Emphasis\\\"\\u003e\\u0026plusmn;\\u003c/span\\u003e\\u0026thinsp;0.79). Most women opting for surveillance state that they adhere to the recommended scheme (4.69\\u0026thinsp;\\u003cspan type=\\\"Underline\\\" class=\\\"Underline\\\" name=\\\"Emphasis\\\"\\u003e\\u0026plusmn;\\u003c/span\\u003e\\u0026thinsp;0.78).\\u003c/p\\u003e\"},{\"header\":\"Discussion\",\"content\":\"\\u003cp\\u003eIn the current study, the major determinants for opting to undergo RRM in Israeli cancer-free \\u003cem\\u003eBRCA\\u003c/em\\u003e PV carriers were active BC risk reduction, fear of developing BC, and the wish not to become a burden on the family in case cancer does develop. Additionally, family history of cancer, especially any relative diagnosed with BC\\u0026thinsp;\\u0026lt;\\u0026thinsp;45 years, primarily in \\u003cem\\u003eBRCA1\\u003c/em\\u003e PV carriers genotyped in the 30\\u0026ndash;50 year age group were more likely to opt for RRM. Notably, the effect of family physician and spiritual leaders \\u0026ndash; were minimal at best.\\u003c/p\\u003e \\u003cp\\u003eThe findings reported herein from a sizeable cohort of cancer-free Israeli \\u003cem\\u003eBRCA\\u003c/em\\u003e PV carriers reinforce several well-established determinants previously reported, while adding novel granularity\\u0026mdash;particularly around family-history sub-patterns, and the minimal influence of primary-care physicians or religious leaders. Prospective psychological evaluations and mixed-methods analyses demonstrate that fear of BC, persistent cancer-related worry, and the perception that RRM provides the most definitive form of risk reduction repeatedly predict surgical decision-making. Isselhard et al., [\\u003cspan citationid=\\\"CR15\\\" class=\\\"CitationRef\\\"\\u003e15\\u003c/span\\u003e] and Morgan et al., [\\u003cspan citationid=\\\"CR22\\\" class=\\\"CitationRef\\\"\\u003e22\\u003c/span\\u003e] describe substantial emotional relief following RRM, a contrast to the ongoing anxiety reported by women opting for surveillance. These findings are in line with our data, where BC risk reduction was the highest-ranked motivator and quantitatively measured cancer worry was significantly elevated among women choosing RRM. Similar patterns have been reported in two German prospective cohorts [\\u003cspan citationid=\\\"CR15\\\" class=\\\"CitationRef\\\"\\u003e15\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR28\\\" class=\\\"CitationRef\\\"\\u003e28\\u003c/span\\u003e], higher baseline anxiety, health concerns, and cancer-related distress were independently associated with opting for RRM over intensified surveillance. In a U.S. NCI cohort, Portnoy and coworkers [\\u003cspan citationid=\\\"CR29\\\" class=\\\"CitationRef\\\"\\u003e29\\u003c/span\\u003e] showed that elevated cancer worry\\u0026mdash;amplified by false-positive screening experiences\\u0026mdash;predicted subsequent RRM among \\u003cem\\u003eBRCA\\u003c/em\\u003e PV carriers, while Padamsee et al., [\\u003cspan citationid=\\\"CR30\\\" class=\\\"CitationRef\\\"\\u003e30\\u003c/span\\u003e] described that high-risk U.S. women explicitly prioritizing \\u0026ldquo;maximal risk reduction\\u0026rdquo; and \\u0026ldquo;relief from cancer fear\\u0026rdquo; when choosing RRM over chemoprevention or surveillance. Taken together, data from Germany, the United States, and now Israel, indicate that prevention-driven and fear-driven motivations for RRM are remarkably consistent across differing cultural and health-system contexts.\\u003c/p\\u003e \\u003cp\\u003eFamily-history intensity, both in terms of number of affected first-degree relatives and the age at cancer onset has repeatedly been linked with RRM. Gilbert et al. [\\u003cspan citationid=\\\"CR31\\\" class=\\\"CitationRef\\\"\\u003e31\\u003c/span\\u003e] reported that RRM was more common among women with multiple BCs in FDR and especially when OvC occurred in an FDR before age 40. Singh et al., [\\u003cspan citationid=\\\"CR32\\\" class=\\\"CitationRef\\\"\\u003e32\\u003c/span\\u003e] similarly showed that having relatives who died of BC significantly influenced the decision for RRM or RRSO. In Dean\\u0026rsquo;s qualitative study of BRCA-positive women [\\u003cspan citationid=\\\"CR33\\\" class=\\\"CitationRef\\\"\\u003e33\\u003c/span\\u003e], \\u0026ldquo;traumatic family cancer memories\\u0026rdquo; (e.g., watching a mother or aunt die young) were a central source of familial uncertainty and a powerful driver of RRM. Dean and Fisher\\u0026rsquo;s later work [\\u003cspan citationid=\\\"CR34\\\" class=\\\"CitationRef\\\"\\u003e34\\u003c/span\\u003e] with 46 previvors showed that women who appraise their risk as a \\u0026ldquo;looming danger\\u0026rdquo;\\u0026mdash; manifesting in vivid memories of early, severe family cancers\\u0026mdash;are much more likely to choose risk reducing surgery over surveillance as an uncertainty-management strategy. Hoskins and Greene\\u0026rsquo;s study [\\u003cspan citationid=\\\"CR35\\\" class=\\\"CitationRef\\\"\\u003e35\\u003c/span\\u003e] of young \\u003cem\\u003eBRCA\\u003c/em\\u003e PV carriers who elected early RRM found that many participants explicitly described surgery as a way to sidestep repeating relatives\\u0026rsquo; less favorable clinical outcomes and to spare partners and children the experience of \\u0026ldquo;going through cancer again.\\u0026rdquo; These themes are synthesized in Torrisi et al., study [\\u003cspan citationid=\\\"CR36\\\" class=\\\"CitationRef\\\"\\u003e36\\u003c/span\\u003e] of decision-making for RRM, which highlights family cancer narratives and early losses as core, cross-study motivators for choosing RRM among high-risk women. Our dataset adds further resolution to these previous studies: having an FDR with BC diagnosed\\u0026thinsp;\\u0026lt;\\u0026thinsp;45 years was particularly pronounced among \\u003cem\\u003eBRCA1\\u003c/em\\u003e PV carriers opting for RRM.\\u003c/p\\u003e \\u003cp\\u003eThe rising role of online support groups and \\u003cem\\u003eBRCA\\u003c/em\\u003e \\u0026ldquo;previvor\\u0026rdquo; communities is also noteworthy. In several cohorts, women who participated in in-person or online \\u003cem\\u003eBRCA\\u003c/em\\u003e-carrier communities described that exposure to RRM-positive stories\\u0026mdash;particularly from peers who had already undergone RRM\\u0026mdash;helped reframe the surgery as acceptable, achievable, and even expected. In a support group evaluation study by Bertonazzi et al.,[\\u003cspan citationid=\\\"CR37\\\" class=\\\"CitationRef\\\"\\u003e37\\u003c/span\\u003e] many carriers explicitly stated that hearing others\\u0026rsquo; experiences \\u0026lsquo;helped [them] decide to do a double mastectomy\\u0026rsquo;. Similarly, Dibble et al., [\\u003cspan citationid=\\\"CR38\\\" class=\\\"CitationRef\\\"\\u003e38\\u003c/span\\u003e] found that online support-group engagement provided emotional validation and decisional reinforcement, with RRM-positive discussions lowering psychological resistance and promoting surgery as a normative step for high-risk women. These findings were also outlined by Gaba et al., [\\u003cspan citationid=\\\"CR39\\\" class=\\\"CitationRef\\\"\\u003e39\\u003c/span\\u003e] who reported that pre-menopausal \\u003cem\\u003eBRCA\\u003c/em\\u003e PV carriers frequently relied on online \\u003cem\\u003eBRCA\\u003c/em\\u003e forums, where posts from women satisfied with RRM created a strong social endorsement effect. Morgan and coworkers [\\u003cspan citationid=\\\"CR22\\\" class=\\\"CitationRef\\\"\\u003e22\\u003c/span\\u003e] further demonstrated that support-group use was significantly more common among women who chose RRM than among those who opted for surveillance, highlighting that peer-network engagement is not merely descriptive but selectively clustered around women inclined toward surgery. Together, these studies support the interpretation that peer narratives\\u0026mdash;both digital and in-person\\u0026mdash;can normalize, encourage, and emotionally support the decision to pursue RRM.\\u003c/p\\u003e \\u003cp\\u003eIn our cohort, the influence of family physicians and religious leaders on RRM uptake was uniformly minimal. This pattern is highly consistent with contemporary evidence from other similarly focused studies. Segerer et al., [\\u003cspan citationid=\\\"CR13\\\" class=\\\"CitationRef\\\"\\u003e13\\u003c/span\\u003e] found no independent association between cultural or religious background and the choice of risk reducing surgery among \\u003cem\\u003eBRCA\\u003c/em\\u003e carriers. Similarly, Puski et al., [\\u003cspan citationid=\\\"CR40\\\" class=\\\"CitationRef\\\"\\u003e40\\u003c/span\\u003e] demonstrated that \\u003cem\\u003eBRCA\\u003c/em\\u003e carriers overwhelmingly identified genetics specialists and close family members\\u0026mdash;rather than primary-care or other non-specialist clinicians\\u0026mdash;as the meaningful influencers in risk-management decisions. Qualitative research further supports these findings: Graham et al., [\\u003cspan citationid=\\\"CR41\\\" class=\\\"CitationRef\\\"\\u003e41\\u003c/span\\u003e] showed that women perceive RRM as a personally owned, self-directed act of controlling hereditary cancer risk, with health professionals operating primarily as information providers rather than decisional authorities. Hesse-Biber and An [\\u003cspan citationid=\\\"CR42\\\" class=\\\"CitationRef\\\"\\u003e42\\u003c/span\\u003e] likewise reported that women\\u0026rsquo;s post-testing decisions are shaped predominantly by personal risk perceptions, family cancer narratives, and social-network experiences, with minimal impact from spiritual leaders or non-specialist clinicians. From a familial-cancer perspective, our findings underscore that decisions regarding RRM are embedded within lived family cancer narratives rather than being driven primarily by formal medical authority. This observation reinforces the importance of incorporating family history context, peer support exposure, and cancer-related worry into genetic counselling frameworks for \\u003cem\\u003eBRCA\\u003c/em\\u003e carriers.\\u003c/p\\u003e \\u003cp\\u003eWhile the current study combined with previous research that focused on RRM Vs. non-surgical options provide some insights, several gaps need to be addressed to facilitate future studies: focus only on cancer free \\u003cem\\u003eBRCA\\u003c/em\\u003e carriers (exclude those who were already diagnosed with BC electing for contralateral risk reducing mastectomy); a longitudinal, multiple time contact points, prospective study is urgently needed; expand such RRM decision affecting factors studies to culturally divergent populations; unified, validated RRM focused questionnaires with identical parameters collected to enable a more precise comparison between diverse populations; deeper qualitative and mixed-methods research may help elucidate the variety of psychological, body-image, partner/family influence, decisional conflict and regret over time. In this context, although the cohort reported herein was NGO-based, uptake rates and decision patterns were comparable to those reported in population-based European cohorts, supporting external validity.\\u003c/p\\u003e \\u003cp\\u003eIn conclusion, our data reinforces a multifactorial model of RRM decision-making: one in which perceived risk, lived family experience, emotional burden, and support networks are more important in RRM decision than external authority non professional figures. Future prospective studies in ethnically diverse populations are needed to implement these results in order to improve genetic counselling, individualized risk communication, and patient-centered decision-support tools.\\u003c/p\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003eAcknowledgements\\u003c/strong\\u003e\\u003cbr\\u003e\\u0026nbsp;The authors thank all Good Genes NGO members for their participation in this study.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eFunding statement\\u003c/strong\\u003e\\u003cbr\\u003e\\u0026nbsp;This research received no specific grant from any funding agency in the public, commercial, or not‑for‑profit sectors.”\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAuthor contributions\\u003c/strong\\u003e\\u003cbr\\u003e\\u0026nbsp;KA, LM and EF conceived and designed the study. KA, TS and LM coordinated data collection and participant recruitment. YL and EF performed the statistical analyses and interpreted the data. YL drafted the first version of the manuscript. KA, TS, LM and EF critically reviewed and revised the manuscript for important intellectual content. All authors read and approved the final manuscript.”\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConflict of interest / Competing interests\\u003c/strong\\u003e\\u003cbr\\u003e\\u0026nbsp;The authors declare that they have no conflicts of interest.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eEthics approval and consent\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe study was approved by the local ethics committee (SMC 1492-14), and all participants consented for participation prior to completing the questionnaire, as implied by consent completion, in compliance with the IRB approved protocol.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eData availability\\u003c/strong\\u003e\\u003cbr\\u003e\\u0026nbsp;De-identified data that support the findings of this study are available from the corresponding author upon reasonable request.\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\u003cli\\u003e\\u003cspan\\u003eKuchenbaecker KB, Hopper JL, Barnes DR, Phillips KA, Mooij TM, Roos-Blom MJ et al (2017) Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers. JAMA 317(23):2402\\u0026ndash;2416\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eKatsika L, Boureka E, Kalogiannidis I, Tsakiridis I, Tirodimos I, Lallas K, Tsimtsiou Z, Dagklis T (2024) Screening for Breast Cancer: A Comparative Review of Guidelines. Life (Basel) 14(6):777. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.3390/life14060777\\u003c/span\\u003e\\u003cspan address=\\\"10.3390/life14060777\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eNCCN guidelines - \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003ehttps://www.nccn.org/professionals/physician_gls/pdf/breast-screening.pdf\\u003c/span\\u003e\\u003cspan address=\\\"https://www.nccn.org/professionals/physician_gls/pdf/breast-screening.pdf\\\" targettype=\\\"URL\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eSessa C, Balma\\u0026ntilde;a J, de Azambuja E, Sonke GS, Paluch-Shimon S, Cardoso F et al (2023) Risk reduction and screening of cancer in hereditary breast\\u0026ndash;ovarian cancer syndromes: ESMO clinical practice guideline. Ann Oncol 34(1):33\\u0026ndash;47. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1016/j.annonc.2022.10.004\\u003c/span\\u003e\\u003cspan address=\\\"10.1016/j.annonc.2022.10.004\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003ehttps://\\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e\\u003c/span\\u003e\\u003cspan address=\\\"http://www.nccn.org/guidelines/guidelines\\\" targettype=\\\"URL\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e-detail?category=2\\u0026amp;id=1545\\u0026amp;utm_source\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eGaba F, Piek J, Manchanda R, Dyer R, Smrkolj Š, Sarid Mogilevsky S et al (2023) Breast cancer risk and breast-cancer-specific mortality following risk-reducing salpingo-oophorectomy in BRCA carriers: A systematic review and meta-analysis. Cancers (Basel) 15(5):1625. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.3390/cancers15051625\\u003c/span\\u003e\\u003cspan address=\\\"10.3390/cancers15051625\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eMetcalfe K, Eisen A, Senter L, Armel S, Bordeleau L, Meschino WS et al (2019) International trends in the uptake of cancer risk reduction strategies in women with a BRCA1 or BRCA2 mutation. Br J Cancer 121(1):15\\u0026ndash;21\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eWillert CB, Mellemkj\\u0026aelig;r L, Tolver A, Gerdes A-MA, Rosth\\u0026oslash;j S, Wadt K et al (2025) Time trends, uptake, and oncological effects of risk-reducing surgeries in 3067 Danish BRCA1/2 carriers: a population-based study with matched controls. Breast Cancer Res Treat. [Epub ahead of print] \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1007/s10549-025-07821-4\\u003c/span\\u003e\\u003cspan address=\\\"10.1007/s10549-025-07821-4\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eHyldebrandt HK, Stormorken AT, Vitelli V, M\\u0026aelig;hle L, Schlichting E, Grindedal EM (2025) Risk reducing mastectomy in Norwegian BRCA1/2 carriers. Eur J Surg Oncol 51(3):109571. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1016/j.ejso.2024.109571\\u003c/span\\u003e\\u003cspan address=\\\"10.1016/j.ejso.2024.109571\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eEvans DGR, Howell A, Ward D, Prestwich F, Betterton J, Duffy SW et al (2021) Twenty-year experience of breast-cancer risk management in the U.K. familial-risk program. J Med Genet 58(5):329\\u0026ndash;336. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1136/jmedgenet-2020-107387\\u003c/span\\u003e\\u003cspan address=\\\"10.1136/jmedgenet-2020-107387\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eZimovjanova M, Skapa P, Fedorova L, Horak J, Brandejsova J, Foretova L (2023) Uptake and effectiveness of risk-reducing surgeries in unaffected female BRCA1 and BRCA2 carriers: A single institution experience in the Czech Republic. Cancers (Basel) 15(4):1072. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.3390/cancers15041072\\u003c/span\\u003e\\u003cspan address=\\\"10.3390/cancers15041072\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eSim\\u0026otilde;es Corr\\u0026ecirc;a Galendi JS, Kautz-Freimuth S, Stock S, M\\u0026uuml;ller D (2022) Uptake rates of risk-reducing surgeries for women at increased risk of hereditary breast and ovarian cancer applied to cost-effectiveness analyses: a scoping systematic review. Cancers (Basel) 14(7):1786. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.3390/cancers14071786\\u003c/span\\u003e\\u003cspan address=\\\"10.3390/cancers14071786\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eSegerer R, Steinke-Lange V, Kurz C, Dworniczak B, Rahner N, Hinterberger-Fischer M et al (2020) Factors impacting on decision-making towards prophylactic surgeries in BRCA mutation carriers and women with familial predisposition. Breast Care (Basel) 15(3):253\\u0026ndash;259. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1159/000503370\\u003c/span\\u003e\\u003cspan address=\\\"10.1159/000503370\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003ePark S, Kim Y, Kim S (2020) Factors associated with the decision to undergo risk-reducing salpingo-oophorectomy among women at high risk for hereditary breast and ovarian cancer: a systematic review. Korean J Women Health Nurs 26(4):285\\u0026ndash;299. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.4069/kjwhn.2020.11.19\\u003c/span\\u003e\\u003cspan address=\\\"10.4069/kjwhn.2020.11.19\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eIsselhard A, Niels T, Antoniadis A, Becker K, Kohls E, Nothacker J et al (2023) Psychological distress and decision-making factors for prophylactic bilateral mastectomy in cancer-unaffected BRCA1/2 pathogenic variant carriers. Psychooncology 32(4):640\\u0026ndash;648. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1002/pon.6111\\u003c/span\\u003e\\u003cspan address=\\\"10.1002/pon.6111\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eChavarri-Guerra Y, Villarreal-Garza C, Lazcano-Ponce E, Banegas MP, Flores-Luna L, Komenaka I et al (2024) Uptake of risk-reducing surgeries in an international real-world cohort of Hispanic women. JCO Glob Oncol 10:e2400097. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1200/GO.24.00097.​\\u003c/span\\u003e\\u003cspan address=\\\"10.1200/GO.24.00097.​\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eMcGarrigle SA, Prizeman G, Spillane C, Byrne N, Drury A et al (2024) Decision aids for female \\u003cem\\u003eBRCA\\u003c/em\\u003e mutation carriers: a scoping review. BMJ Open 14(6):e076876. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1136/bmjopen-2023-076876\\u003c/span\\u003e\\u003cspan address=\\\"10.1136/bmjopen-2023-076876\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eLaitman Y, Feng B, Zamir IM, Levi R, Friedman E, Kaufman B et al (2014) Rates of risk-reducing surgery in Israeli BRCA1 and BRCA2 mutation carriers. Clin Genet 85(1):68\\u0026ndash;71. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1111/cge.12149\\u003c/span\\u003e\\u003cspan address=\\\"10.1111/cge.12149\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eKram V, Peretz T, Sagi M, Levy-Lahad E, Friedman E (2006) Acceptance of preventive surgeries by Israeli women who had undergone BRCA testing. Fam Cancer 5(4):327\\u0026ndash;335. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1007/s10689-006-0002-z\\u003c/span\\u003e\\u003cspan address=\\\"10.1007/s10689-006-0002-z\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eNahshon C, Segev Y, Schmidt M, Lavie O (2024) Attitude of BRCA1/2 mutation carriers towards surgical risk reduction for breast, ovarian and uterine cancer: still much to be done. Int J Gynecol Cancer 34(2):260\\u0026ndash;266. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1136/ijgc-2023-004801\\u003c/span\\u003e\\u003cspan address=\\\"10.1136/ijgc-2023-004801\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eMesa-Chavez F, Chavarri-Guerra Y, Aguilar-Y-Mendez D, Becerril-Gaitan A, Vaca-Cartagena BF, Carrillo-Bedoya A et al (2024) Uptake of Risk-Reducing Measures, Cascade Testing, and Related Challenges Among Carriers of Breast Cancer-Associated Germline Pathogenic Variants in Mexico. JCO Glob Oncol 10:e2300417. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1200/GO.23.00417\\u003c/span\\u003e\\u003cspan address=\\\"10.1200/GO.23.00417\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eMorgan J, Lugg-Widger F, Rylance A, Rice C, Lewis K, Edwards A et al (2024) Psychosocial outcomes after varying risk management strategies in women at increased familial breast cancer risk: A mixed methods study of patient and partner outcomes. Ann R Coll Surg Engl 106(1):78\\u0026ndash;91. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1308/rcsann.2023.0042\\u003c/span\\u003e\\u003cspan address=\\\"10.1308/rcsann.2023.0042\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eModaffari P, Ponzone R, Ferrari A, Cipullo I, Liberale V, D'Alonzo M, Maggiorotto F, Biglia N (2019) Concerns and Expectations of Risk-Reducing Surgery in Women with Hereditary Breast and Ovarian Cancer Syndrome. J Clin Med 8(3):313. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.3390/jcm8030313\\u003c/span\\u003e\\u003cspan address=\\\"10.3390/jcm8030313\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eMann HB, Whitney DR (1947) On a test of whether one of two random variables is stochastically larger than the other. Ann Math Stat 18(1):50\\u0026ndash;60\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eHochberg Y, Benjamini Y (1990) More powerful procedures for multiple significance testing. Stat Med 9(7):811\\u0026ndash;818. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1002/sim.4780090710\\u003c/span\\u003e\\u003cspan address=\\\"10.1002/sim.4780090710\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eNorman G (2010) Likert scales, levels of measurement and the laws of statistics. Adv Health Sci Educ 15(5):625\\u0026ndash;632\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eAkoglu H (2018) User's guide to correlation coefficients. Turk J Emerg Med 18(3):91\\u0026ndash;93. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1016/j.tjem.2018.08.001\\u003c/span\\u003e\\u003cspan address=\\\"10.1016/j.tjem.2018.08.001\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eDick J, Ablasser G, Ehlers M, Steinemann N, Schulze S, Preisler-Adams S et al (2022) Psychological factors and the uptake of preventative measures in BRCA1/2 pathogenic variant carriers: Results of a prospective cohort study. Hered Cancer Clin Pract 20(1):38. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1186/s13053-022-00244-y\\u003c/span\\u003e\\u003cspan address=\\\"10.1186/s13053-022-00244-y\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003ePortnoy DB, Loud JT, Han PKJ, Mai PL, Greene MH (2015) Effects of false-positive cancer screenings and cancer worry on risk-reducing surgery among BRCA1/2 mutation carriers. Health Psychol 34(7):709\\u0026ndash;717. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1037/hea0000156\\u003c/span\\u003e\\u003cspan address=\\\"10.1037/hea0000156\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003ePadamsee TJ, Wills CE, Yee LD, Paskett ED (2017) Decision making for breast cancer prevention among women at elevated risk. Breast Cancer Res 19(1):34. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1186/s13058-017-0826-5\\u003c/span\\u003e\\u003cspan address=\\\"10.1186/s13058-017-0826-5\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eGilbert E, Zabor EC, Stempel M, Mangino DA, Kellick MG, Morrow M et al (2017) Differences among a modern cohort of BRCA mutation carriers choosing bilateral prophylactic mastectomies compared to breast surveillance. Ann Surg Oncol 24(10):3048\\u0026ndash;3054. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1245/s10434-017-5976-2\\u003c/span\\u003e\\u003cspan address=\\\"10.1245/s10434-017-5976-2\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eSingh K, Lester J, Karlan B, Bresee C, Geva T, Gordon O (2013) Impact of family history on choosing risk-reducing surgery among BRCA mutation carriers. Am J Obstet Gynecol 208(4):329. .e1-6\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eDean M (2016) It\\u0026rsquo;s not if I get cancer, it\\u0026rsquo;s when I get cancer: BRCA-positive patients\\u0026rsquo; (un)certain health experiences regarding hereditary breast and ovarian cancer risk. Soc Sci Med 163:21\\u0026ndash;27. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1016/j.socscimed.2016.06.039\\u003c/span\\u003e\\u003cspan address=\\\"10.1016/j.socscimed.2016.06.039\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eDean M, Fisher CL (2019) Uncertainty and previvors\\u0026rsquo; cancer risk management: understanding the decision-making process. J Appl Commun Res 47(4). \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1080/00909882.2019.1657236\\u003c/span\\u003e\\u003cspan address=\\\"10.1080/00909882.2019.1657236\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eHoskins LM, Greene MH (2012) Anticipatory loss and early mastectomy for young female BRCA1/2 mutation carriers. Qual Health Res 22(12):1633\\u0026ndash;1646. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1177/1049732312458182\\u003c/span\\u003e\\u003cspan address=\\\"10.1177/1049732312458182\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eTorrisi C, Wareg NK, Brandt Anbari A (2024) Decision-making for bilateral risk-reducing mastectomy for an increased lifetime breast cancer risk: a qualitative metasynthesis. Psychooncology 33(3):e6311. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1002/pon.6311\\u003c/span\\u003e\\u003cspan address=\\\"10.1002/pon.6311\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eBertonazzi B, Bellati F, Ricciardi E, Capriglione S, Perrone E, Di Meglio A et al (2022) Outcomes of support groups for carriers of BRCA1/2. Fam Cancer 21(1):51\\u0026ndash;61\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eDibble KE, Donorfio LKM, Britner PA, Bellizzi KM (2022) Perceptions and care Recommendations from Previvors: Qualitative analysis of female BRCA1/2 mutation Carriers' experience with genetic testing and counseling. Gynecol Oncol Rep 41:100989. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1016/j.gore.2022.100989\\u003c/span\\u003e\\u003cspan address=\\\"10.1016/j.gore.2022.100989\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eGaba F, Manchanda R, Smrkolj S, Sarid Mogilevsky S, Seckl MJ, McCluggage WG et al (2021) Surgical decision-making in premenopausal BRCA carriers: The influence of online support forums. Breast J 27(2):179\\u0026ndash;188\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003ePuski A, Hovick S, Senter L, Toland AE (2018) Involvement and Influence of Healthcare Providers, Family Members, and Other Mutation Carriers in the Cancer Risk Management Decision-Making Process of BRCA1 and BRCA2 Mutation Carriers. J Genet Couns 27(5):1291\\u0026ndash;1301. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1007/s10897-018-0254-4\\u003c/span\\u003e\\u003cspan address=\\\"10.1007/s10897-018-0254-4\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eGraham R, Owens M, Priest H, Hutton S (2018) Constructions of Decision Making for Risk-Reducing Mastectomy. Qual Health Res 28(10):1595\\u0026ndash;1609. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1177/1049732318785372\\u003c/span\\u003e\\u003cspan address=\\\"10.1177/1049732318785372\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eHesse-Biber S, An C (2016) Genetic testing and post-testing decision making among BRCA-positive mutation women: A psychosocial approach. J Genet Couns 25(5):978\\u0026ndash;992. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003e10.1007/s10897-015-9929-2\\u003c/span\\u003e\\u003cspan address=\\\"10.1007/s10897-015-9929-2\\\" targettype=\\\"DOI\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/span\\u003e\\u003c/li\\u003e\\u003c/ol\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":true,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":false,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":true,\"isAuthorSuppliedPdf\":false,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":false,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"familial-cancer\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"fame\",\"sideBox\":\"Learn more about [Familial Cancer](http://link.springer.com/journal/10689)\",\"snPcode\":\"10689\",\"submissionUrl\":\"https://submission.nature.com/new-submission/10689/3\",\"title\":\"Familial Cancer\",\"twitterHandle\":\"\",\"acdcEnabled\":true,\"dfaEnabled\":true,\"editorialSystem\":\"em\",\"reportingPortfolio\":\"Springer Hybrid\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":false},\"keywords\":\"BRCA pathogenic variant carriers, breast cancer risk, risk reducing mastectomy, Surveillance decisions\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-8523281/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-8523281/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003cp\\u003eWomen harboring pathogenic variant (PV) in the \\u003cem\\u003eBRCA1\\u003c/em\\u003e or \\u003cem\\u003eBRCA2\\u003c/em\\u003e genes (=\\u0026thinsp;\\u003cem\\u003eBRCA\\u003c/em\\u003e) have an elevated lifetime risk for breast cancer (BC). One of the main options for active breast cancer risk reduction is bilateral risk-reducing mastectomy (RRM). Understanding the factors influencing that decision is important for genetic-counselling and risk mitigation strategy planning. A structured questionnaire was circulated to \\u003cem\\u003eBRCA\\u003c/em\\u003e carriers, members of the Good Genes NGO in Israel. Data on RRM uptake and timing, factors previously reported to be associated with decision to undergo RRM (e.g., psychosocial, family history, counselling/health-system factors) were obtained. Comparison between carriers who elected to undergo RRM with those who opted for early detection schemes were performed using logistic regression and chi square statistical analyses. Of cancer free women (n\\u0026thinsp;=\\u0026thinsp;391), 272 (69.6%) elected to adhere to the recommended surveillance scheme and 119 (30.4%) elected to undergo RRM. The major reasons for electing RRM over surveillance were active BC risk reduction (4.96\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.23), fear of developing BC (4.86\\u0026thinsp;\\u003cspan type=\\\"Underline\\\" class=\\\"Underline\\\" name=\\\"Emphasis\\\"\\u003e\\u0026plusmn;\\u003c/span\\u003e\\u0026thinsp;0.50), and having at least one relative with BC diagnosed under age 45 years. Support group discussions emerged as a stronger determinant of RRM uptake than primary care physician or religious guidance. In conclusion, among healthy Israeli \\u003cem\\u003eBRCA\\u003c/em\\u003e carriers the decision to undergo RRM was influenced by a complex interplay of factors \\u0026ndash; active BC risk reduction, fear of cancer diagnosis in the context of having one relative with early onset BC and support group discussions were the major drivers of RRM in Israeli \\u003cem\\u003eBRCA1\\u003c/em\\u003e carriers.\\u003c/p\\u003e\",\"manuscriptTitle\":\"Factors influencing uptake of risk-reducing mastectomy among unaffected Israeli BRCA1/BRCA2 pathogenic variant carriers\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2026-01-23 10:25:55\",\"doi\":\"10.21203/rs.3.rs-8523281/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0},{\"type\":\"decision\",\"content\":\"Revision requested\",\"date\":\"2026-04-23T10:14:49+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorInvitedReview\",\"content\":\"\",\"date\":\"2026-03-23T15:54:02+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewerAgreed\",\"content\":\"65565687455870349447523991307933034972\",\"date\":\"2026-03-23T15:35:18+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewerAgreed\",\"content\":\"125487285046602055404040459207536570495\",\"date\":\"2026-03-10T15:19:14+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewerAgreed\",\"content\":\"198557211949227092775014316098759521126\",\"date\":\"2026-02-05T07:46:55+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewerAgreed\",\"content\":\"174217071153982574598813296330593754261\",\"date\":\"2026-02-03T16:35:47+00:00\",\"index\":\"hide\",\"fulltext\":\"\"},{\"type\":\"reviewersInvited\",\"content\":\"\",\"date\":\"2026-01-21T12:43:48+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorAssigned\",\"content\":\"\",\"date\":\"2026-01-13T12:32:57+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"checksComplete\",\"content\":\"\",\"date\":\"2026-01-13T12:26:47+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"submitted\",\"content\":\"Familial Cancer\",\"date\":\"2026-01-05T15:51:13+00:00\",\"index\":\"\",\"fulltext\":\"\"}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"familial-cancer\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"fame\",\"sideBox\":\"Learn more about [Familial Cancer](http://link.springer.com/journal/10689)\",\"snPcode\":\"10689\",\"submissionUrl\":\"https://submission.nature.com/new-submission/10689/3\",\"title\":\"Familial Cancer\",\"twitterHandle\":\"\",\"acdcEnabled\":true,\"dfaEnabled\":true,\"editorialSystem\":\"em\",\"reportingPortfolio\":\"Springer Hybrid\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":false}}],\"origin\":\"\",\"ownerIdentity\":\"dcd9229a-1729-402d-b70c-02ed66ecde2e\",\"owner\":[],\"postedDate\":\"January 23rd, 2026\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"under-review\",\"subjectAreas\":[],\"tags\":[],\"updatedAt\":\"2026-05-01T07:39:59+00:00\",\"versionOfRecord\":[],\"versionCreatedAt\":\"2026-01-23 10:25:55\",\"video\":\"\",\"vorDoi\":\"\",\"vorDoiUrl\":\"\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-8523281\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-8523281\",\"identity\":\"rs-8523281\",\"version\":[\"v1\"]},\"buildId\":\"XKTyCvWXoU3ODBz1xrDgd\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}