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Objectives: Risk-reducing mastectomy (RRM) is one of key prevention strategies in female carriers of germline BRCA pathogenic/likely pathogenic variants (PV/LPV). We retrospectively investigated the rate, timing and longitudinal trends of bilateral RRM uptake and the incidence and types of cancers among unaffected BRCA carriers who underwent genetic counseling at the Institute of Oncology Ljubljana in Slovenia., Materials and Methods: Female BRCA carriers without personal history of cancer were included in the study. Clinical data on PV/LPV type, date of RRM, type of reconstructive procedure, occult carcinoma and histopathology results was collected and analyzed., Results: Of the 346 unaffected BRCA carriers (median age 43 years, 70% BRCA1, 30% BRCA2, median follow-up 46 months) who underwent genetic testing between October 1999 and December 2019, 25.1% had a RRM (range 35-50 years, median age at surgery 38 years). A significant difference in time to prophylactic surgery between women undergoing RRM only vs. women undergoing RRM combined with risk-reducing salpingo-oophorectomy was observed (22.6 vs 8.7 months, p = 0.0009). We observed an upward trend in the annual uptake in line with the previously observed Angelina Jolie effect. In 5.7% of cases, occult breast cancer was detected. No women developed breast cancer after RRM. Women who did not opt for surgical prevention developed BRCA1/2-related cancers (9.3%)., Conclusion: The uptake of RRM among unaffected BRCA carriers is 25.1% and is similar to our neighboring countries. No women developed breast cancer after RRM while women who did not opt for surgical prevention developed BRCA1/2 related cancers in 9.3% of cases. The reported data may provide meaningful aid for carriers when deciding on an optimal prevention strategy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

BRCA1/BRCA2 genes were discovered in early 1990s and clinical testing for these has been available since the mid-1990s. National Institute of Health and Care Excellence (NICE) and other international guidelines recommend genetic-testing at a ~10% probability threshold of carrying a BRCA-mutation. A detailed three generation family-history (FH) of cancer is used within complex mathematical models (e.g. BOADICEA, BRCAPRO, Manchester-Scoring-System) or through standardized clinical-criteria to identify individuals who fulfil this probability threshold and can be offered genetic-testing. Identification of unaffected carriers is important given the high risk of cancer in these women and the effective options available for clinical management which can reduce cancer risk, improve outcomes and minimise burden of disease. This article is protected by copyright. All rights reserved., (This article is protected by copyright. All rights reserved.)

The last 5 years have brought significant innovation and advancement in the genetics of breast cancer. This clinical opinion aims to summarize and update current approaches to the care of women at risk for a hereditary predisposition to breast cancer. Implications of the BRCA mutation and several other hereditary syndromes will be discussed. Risk assessment and criteria for referral to cancer genetic professionals as well as high-risk screening and prophylactic options will be reviewed. Finally, the newly available genetic cancer panels and implications of mutations in some of these lesser known genes will be discussed. As the field of cancer genetics continues to evolve, the education of medical students, residents, and faculty will be paramount to identify appropriate candidates for genetic counseling and testing in conjunction with cancer genetic professionals., (Copyright © 2015 Elsevier Inc. All rights reserved.)

There is a significant variation in the uptake of cancer risk reducing options by women with a BRCA1 or BRCA2 mutation. It is currently unclear why these differences exist and it is possible that recommendations vary between providers and these influence patient decisions. Eligible health care providers who provide genetic counseling for hereditary breast and ovarian cancer families in Canada were identified. Each provider was asked to complete a study specific questionnaire that included their opinion of various cancer risk reduction options and their recommendations for specific cases. Respondents recommended prophylactic oophorectomy more often than prophylactic mastectomy or tamoxifen for women with a BRCA1 or BRCA2 mutation (p < 0.0001). Fewer than half of the respondents agreed with the recommendation for prophylactic mastectomy, and a minority of the respondents supported the recommendation for tamoxifen for chemoprevention. The majority of Canadian genetics health care providers adhere to the National Comprehensive Cancer Network (NCCN) Guideline of recommending prophylactic oophorectomy to mutation carriers, however, the minority of genetics health care providers recommend either prophylactic mastectomy or tamoxifen., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The objective of this study was to describe the experience of genetic testing in Austrian women with a BRCA1 or BRCA2 mutation in terms of preventive measures taken and incident cancers diagnosed. We collected clinical information on 246 Austrian women with a BRCA1 or BRCA2 mutation tested between 1995 and 2012 and followed 182 of them for an average of 6.5 years. Of the 90 women who were cancer-free at baseline, 21.4% underwent preventive bilateral mastectomy, 46.1% had preventive bilateral salpingo-oophorectomy, and 1 took tamoxifen; 58.8% of the at-risk women underwent at least one screening breast magnetic resonance imaging (MRI). Of the 85 women with breast cancer, 69.4% had a unilateral mastectomy or lumpectomy and 30.6% had a contralateral mastectomy. In the follow-up period, 14 new invasive breast cancers (6 first primary and 8 contralateral), 1 ductal carcinoma in situ case, 2 incident ovarian cancer cases, and 1 peritoneal cancer were diagnosed. In Austria, the majority of healthy women with a BRCA1 or BRCA2 mutation opt for preventive oophorectomy and MRI screening to manage their breast cancer risk; few have preventive mastectomy or take tamoxifen., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The frequency of BRCA1 and BRCA2 mutations is higher in Israel than in almost all other countries. One strategy to reduce the burden of hereditary breast and ovarian cancers is to offer genetic testing followed by risk-reducing surgery (mastectomy and salpingo-oophorectomy) for mutation carriers. The extent to which Israeli women who carry mutations undergo these surgeries is not well characterized. Israeli women who are BRCA1 or BRCA2 mutation carriers and followed at a single high-risk clinic were asked to complete a questionnaire detailing their clinical histories at the time of genetic results disclosure and a follow-up questionnaire was completed 18 or more months thereafter. A total of 205 mutation carriers completed the questionnaires. Of 170 women with no cancer history, 84 (49%) had a risk-reducing bilateral salpingo-oophorectomy and 22 (13%) had a risk-reducing mastectomy. Five of 35 (14.3%) women with breast cancer opted for contralateral mastectomy. Approximately one half of Israeli women with a BRCA1 or BRCA2 mutation opt for risk-reducing oophorectomy, but the rate of risk-reducing mastectomy is only 13%., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To estimate the prevalence of the use of cancer risk-reducing measures among Australian BRCA1 and BRCA2 mutation carriers., Design, Setting and Participants: Prospective follow-up of female carriers of BRCA1 or BRCA2 mutations who had no personal history of cancer and were enrolled in a multiple-case breast cancer family cohort study (kConFab). Data, including cancer events and uptake of risk-reducing surgery and medication were collected by self-report at cohort entry and 3 yearly thereafter. Surgery was confirmed from pathology and medical records. Women were followed up from enrolment until cancer diagnosis, date of last follow-up, or death. Data were collected from 3 November 1997 to 21 May 2012., Main Outcome Measures: Uptake of risk-reducing surgery and/or medication., Results: Of 175 BRCA1 and 150 BRCA2 mutation carriers (median age, 37 years at cohort enrolment), 69 (21%) underwent risk-reducing mastectomy, 125 (38%) underwent risk-reducing bilateral salpingo-oophorectomy and nine (3%) participated in a clinical trial of risk-reducing medication, during 2447 person-years of follow-up (median follow-up, 9 years). Sixty-eight women (21%) reported incident cancers, including 52 breast cancers and nine ovarian cancers (defined in this article as high-grade serous cancers of the ovary, fallopian tube or peritoneum)., Conclusions: There is considerable scope to increase the uptake of cancer risk-reducing measures in Australian BRCA1 and BRCA2 mutation carriers. These findings should drive (i) future research into the factors contributing to low uptake in Australia and (ii) changes to policy and practice to help better translate genetic knowledge into reductions in cancer incidence.

Women afflicted by the hereditary breast and ovarian cancer syndrome face complex decisions regarding medical interventions aimed at reducing their risk of ovarian and breast cancer, interventions which in turn may interfere with their fertility and cause early menopause. This review addresses selected topics of importance and controversy in the management of the BRCA mutation carrier, such as psychological well-being and quality of life, breast and ovarian cancer screening, risk-reducing interventions for breast cancer and ovarian cancer, the issue of hysterectomy at the time of the risk-reducing salpingo-oophorectomy, health consequences of early surgical menopause, and safety of hormonal therapy after oophorectomy. The information presented is based on an extensive review of the literature on the selected topics and on the expertise of our multidisciplinary team.

Aims: Advances in genomics may eventually lead to genetic susceptibility screening of the general population, regardless of a personal or familial history of the disease in question. Yet, little is known about clinicians' attitudes toward such programs. We explored attitudes of family practitioners, medical geneticists and genetic counselors toward genetic screening of the general Ashkenazi-Jewish population for the common founder mutations in BRCA1/2 and LRRK2 genes (which increase the risk of hereditary breast/ovarian cancers and Parkinson's disease, respectively)., Methods: Participants (n = 204) completed a specially designed questionnaire, distributed by e-mail, regular mail or in-person., Results: Slightly more than half (52%) were in favor of BRCA screening, while the vast majority (86%) opposed to LRRK2 screening. About two-thirds (68%) of the respondents supported pre-test genetic counseling. Attitudes were largely independent of professional background and sociodemographic characteristics, though a correlation was found with personal interest in genetic self-testing for the above genes. Adverse psychological impact and discrimination in insurance and employment were the major concerns cited by respondents with regard to screening programs., Conclusion: Our findings suggest that the availability of measures for prevention and/or treatment is a major factor in the attitudes of healthcare providers toward population screening for late-onset conditions., (Copyright © 2013 S. Karger AG, Basel.)