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Background: The lifetime risk of pancreatic cancer in women with a germline mutation in BRCA1 and BRCA2 is not well established. In an international prospective cohort of female carriers of BRCA1 and BRCA2 mutations, the cumulative incidence of pancreatic cancer from age 40 until 80 years was estimated., Methods: A total of 8295 women with a BRCA1 or BRCA2 mutation were followed for new cases of pancreatic cancer. Subjects were followed from the date of baseline questionnaire or age 40 years (whichever came last) until a new diagnosis of pancreatic cancer, death from another cause, or date of last follow-up., Results: Thirty-four incident pancreatic cancer cases were identified in the cohort. The annual risk of pancreatic cancer between age 40 and 80 years was 0.04% for BRCA1 carriers and 0.09% for BRCA2 carriers. Via the Kaplan-Meier method, the cumulative incidence from age 40 to 80 years was 2.2% (95% CI, 1.1%-4.3%) for BRCA1 carriers and 2.7% (95% CI, 1.3%-5.4%) for BRCA2 carriers. Only two of the 34 cases reported a first-degree relative with pancreatic cancer (hazard ratio, 4.75; 95% CI, 1.13-19.9; p = .03). Risk factors for pancreatic cancer included alcohol intake and a history of diabetes. The 5-year survival rate for the 34 cases was 8.8%., Conclusions: The lifetime risk of pancreatic cancer is approximately 2% in women with a BRCA1 mutation and 3% for women with a BRCA2 mutation. The poor survival in hereditary pancreatic cancer underscores the need for novel antitumoral strategies., (© 2024 The Author(s). Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Using educational frameworks for learner assessment in genetic counseling (GC) training may help students and supervisors articulate developmentally appropriate clinical skills-based objectives and tasks that align with various stages of training as students work toward achieving entry-level competency. This professional issues case study describes how two GC programs adapted and implemented the RIME (Reporter-Interpreter-Manager-Educator) learner assessment framework, originally designed for medical education, to support and assess students' acquisition of practice-based competencies (PBCs) during clinical fieldwork placements. Each RIME level describes a different set of expectations regarding the skills students should be able to demonstrate based on the level of training they have achieved up to that point in time. In early training, students work mainly on gathering and reporting clinical information (Reporter level). In early to mid-training, students have learned what information to collect from clients and begin to apply the information to generate differential diagnoses (Interpreter level). When students reach the Manager level (typically by mid- to late-training), they can independently develop and implement case management plans tailored to individual cases. The Educator level, which may not be fully attained until after graduation, involves critically evaluating evidence and educating others about new evidence. The following paper describes our experiences incorporating the RIME framework into two GC graduate programs and explains the development of corresponding RIME-based assessment forms that align with the Accreditation Council of Genetic Counseling's 2023 PBCs. Overall, we find that using the RIME framework fosters a growth mindset by enabling students and supervisors to create developmentally appropriate goals and expectations, thereby facilitating assessment and guidance of trainee progress. Despite these perceived benefits, we acknowledge the need for research to evaluate the efficacy of the RIME framework or other learner assessment models in supporting student progression in achieving the GC PBCs., (© 2024 National Society of Genetic Counselors.)

Within the health professions education system, a significant proportion of teaching and learning occurs in the clinical setting. As such, the need to measure effective teaching for accreditation standards, faculty development, merit pay, academic promotion, and for monitoring the safety of the learning environment has led to numerous universities developing instruments to evaluate teaching effectiveness in this context. To date; however, these instruments typically focus on the student perspective, despite evidence demonstrating that student evaluations of teaching (SETs) lack correlation with learning outcomes and are not a true measure of teaching effectiveness. This issue is further exacerbated in small health professional training programs, such as genetic counseling, where clinical teachers may only supervise 1-3 students per year. As a result, not only are SETs more confounded due to small sample sizes, but a direct conflict exists between respecting learner anonymity and providing timely and relevant feedback to faculty. In such contexts, even using SETs to evaluate the nature of the learning environment may be unreliable due to student concerns about identifiability and fear of retaliation for unfavorable evaluation. This paper will review the literature regarding SETs, barriers to this process within the clinical setting, and the unintended downstream consequences. Options for addressing issues related to the use of SETs will be considered, with particular focus on the process of reflection and the use of teaching consultations or peer support groups as a means to improve teaching effectiveness in this learning environment., (© 2024 The Author(s). Journal of Genetic Counseling published by Wiley Periodicals LLC on behalf of National Society of Genetic Counselors.)

Lifelong learning is a term frequently referred to in the training and continuing professional development of genetic counselors. It implies the ability to continuously engage in self-motivated reflection to identify knowledge gaps and develop a learning plan to address identified needs or interests. In contrast to this definition, the path to continuing professional development for most genetic counselors involves attendance at conferences; yet much data suggest that other forms of learning are more effective at leading to practice change and improved patient or quality outcomes. These conflicting ideas beg the question: what is professional learning? A dialogue between two genetic counselor educators, both with advanced training in health professional education, shares personal beliefs regarding lifelong learning in the genetic counseling profession. This discourse represents an authentic conversation that was audio-recorded and transcribed with minimal editing to improve clarity and readability. The views presented in this dialogue are highly personal, yet grounded in educational theory. References are provided to those that desire further reading on the topics discussed. Several authentic learning strategies are described, including communities of practice, peer supervision, and personal learning projects. The authors consider ways to increase knowledge acquisition from conference attendance and discuss how learning on the job becomes embedded in practice. As a result of this discourse, the authors hope to inspire genetic counselors to reflect over their continuing professional development and consider their job as a learning environment that presents rich, ongoing, and unique opportunities for growth. The authors invite and challenge readers to identify learning needs and set goals for themselves to address those needs. For those with interest in education, it is hoped that the conversation sparks new or invigorated interest that will lead to novel or more effective learning opportunities with improved outcomes for patients, students, and colleagues alike., (© 2023 The Authors. Journal of Genetic Counseling published by Wiley Periodicals LLC on behalf of National Society of Genetic Counselors.)

In the general population, physical activity has been associated with a lower risk of several cancers; however, the evidence for ovarian cancer is not clear. It is suggested that early-life physical activity may differentially impact risk. Whether this is true among women at high risk due to a pathogenic variant (mutation) in the BRCA1 or BRCA2 genes has not been evaluated. Thus, we performed a matched case-control study to evaluate the association between adolescent and early-adulthood physical activity and ovarian cancer. BRCA mutation carriers who completed a research questionnaire on various exposures and incident disease and with data available on physical activity were eligible for inclusion. Self-reported activity at ages 12-13, 14-17, 18-22, 23-29, and 30-34 was used to calculate the average metabolic equivalent of task (MET)-hours/week for moderate, vigorous, and total physical activity during adolescence (ages 12-17) and early-adulthood (ages 18-34). Conditional logistic regression was used to estimate the OR and 95% confidence intervals (CI) of invasive ovarian cancer associated with physical activity. This study included 215 matched pairs (mean age = 57.3). There was no association between total physical activity during adolescence (ORhigh vs. low = 0.91; 95% CI: 0.61-1.36; Ptrend = 0.85), early-adulthood (ORhigh vs. low = 0.78; 95% CI: 0.51-1.20; Ptrend = 0.38) and overall (ORhigh vs. low = 0.81; 95% CI: 0.54-1.23; Ptrend = 0.56) and ovarian cancer. Findings were similar for moderate (Ptrend ≥ 0.25) and vigorous (Ptrend ≥ 0.57) activity. These findings do not provide evidence for an association between early-life physical activity and BRCA-ovarian cancer; however, physical activity should continue to be encouraged to promote overall health., Significance: In this matched case-control study, we observed no association between physical activity during adolescence or early-adulthood and subsequent risk of ovarian cancer. These findings do not provide evidence for an association between early-life physical activity and BRCA-ovarian cancer; however, being active remains important to promote overall health and well-being., (© 2023 The Authors; Published by the American Association for Cancer Research.)

Purpose: Chemoprevention with a selective estrogen receptor modulator (tamoxifen or raloxifene) is a non-surgical option offered to high-risk women to reduce the risk of breast cancer. The evidence for tamoxifen benefit is based on trials conducted among predominantly postmenopausal women from the general population and on studies of contralateral breast cancer in women with a pathogenic variant (mutation hereafter) in BRCA1 or BRCA2. Tamoxifen has not been assessed as a primary prevention agent in women with an inherited BRCA mutation., Methods: We conducted a prospective analysis of tamoxifen chemoprevention and the risk of breast cancer in women with a BRCA1 or BRCA2 mutation. Data on tamoxifen (and raloxifene) use was collected by questionnaire and updated biennially. Information on incident cancers was collected by self-report and was confirmed by medical record review. In a matched analysis, we estimated the hazard ratio (HR) and 95% confidence intervals (CI) for developing a first primary breast cancer associated with tamoxifen or raloxifene use, using Cox proportional hazards analysis., Results: There were 4578 unaffected women in the cohort, of whom 137 reported tamoxifen use (3%), 83 reported raloxifene use (2%) and 12 used both drugs (0.3%). Women who used tamoxifen or raloxifene were matched 1:3 with women who used neither drug on year of birth, country of residence, year of study entry and gene (BRCA1 or BRCA2). We generated 202 matched pairs. After a mean follow-up of 6.8 years, there were 22 incident breast cancers diagnosed among tamoxifen/raloxifene users (10.9% of users) and 71 cases diagnosed among non-users (14.3% of non-users; HR = 0.64; 95% CI 0.40-1.03; P = 0.07)., Conclusion: Chemoprevention may be an effective risk-reduction option for BRCA mutation carriers, but further studies with longer follow-up are necessary., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Secondary findings (SFs) identified through genomic sequencing (GS) can offer a wide range of health benefits to patients. Resource and capacity constraints pose a challenge to their clinical management; therefore, clinical workflows are needed to optimise the health benefits of SFs. In this paper, we describe a model we created for the return and referral of all clinically significant SFs, beyond medically actionable results, from GS. As part of a randomised controlled trial evaluating the outcomes and costs of disclosing all clinically significant SFs from GS, we consulted genetics and primary care experts to determine a feasible workflow to manage SFs. Consensus was sought to determine appropriate clinical recommendations for each category of SF and which clinician specialist would provide follow-up care. We developed a communication and referral plan for each category of SFs. This involved referrals to specialised clinics, such as an Adult Genetics clinic, for highly penetrant medically actionable findings. Common and non-urgent SFs, such as pharmacogenomics and carrier status results for non-family planning participants, were directed back to the family physician (FP). SF results and recommendations were communicated directly to participants to respect autonomy and to their FPs to support follow-up of SFs. We describe a model for the return and referral of all clinically significant SFs to facilitate the utility of GS and promote the health benefits of SFs. This may serve as a model for others returning GS results transitioning participants from research to clinical settings., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

The COVID-19 pandemic has led to the rapid adoption of virtual clinic processes and healthcare delivery. Herein, we examine the impact of virtualising genetics services at Canada's largest cancer centre. A retrospective review was conducted to evaluate relevant metrics during the 12 weeks prior to and during virtual care, including referral and clinic volumes, patient wait times and genetic testing uptake. The number of appointments and new patients seen were maintained during virtual care. Likewise, there was a significant increase in the number of patients offered testing during virtual care who did not provide a blood sample (176/180 (97.7%) vs 180/243 (74.1%); p<0.001), and a longer median time from the date of pretest genetic counselling to the date a sample was given (0 vs 11 days; p<0.001). Referral volumes significantly decreased during virtual care (35 vs 22; p<0.001), which was accompanied by a decreased median wait time for first appointment (55 days vs 30 days; p<0.001). The rapid virtualisation of cancer genetic services allowed the genetics clinic to navigate the COVID-19 pandemic without compromising clinical volumes or access to genetic testing. There was a decrease in referral volumes and uptake of genetic testing, which may be attributable to pandemic-related clinical restrictions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: It is not known whether the risk of breast cancer among BRCA1 and BRCA2 mutation carriers after age 60 is high enough to justify intensive screening or prophylactic surgery. Thus, we conducted a prospective analysis of breast cancer risk in BRCA1 and BRCA2 mutation carriers from age 60 until age 80., Methods: Subjects had no history of cancer and both breasts intact at age 60 (n = 699). Women were followed until a breast cancer diagnosis, prophylactic bilateral mastectomy or death. We calculated the annual cancer rate and cumulative incidence of breast cancer (invasive and in situ) from age 60 to age 80. We assessed the associations between hormone replacement therapy, family history of breast cancer and bilateral oophorectomy and breast cancer risk., Results: Over a mean follow-up of 7.9 years, 61 invasive and 20 in situ breast cancers were diagnosed in the cohort. The mean annual rate of invasive breast cancer was 1.8% for BRCA1 mutation carriers and 1.7% for BRCA2 mutation carriers. The cumulative risk of invasive breast cancer from age 60 to 80 was 20.1% for women with a BRCA1 mutation and was 17.3% for women with a BRCA2 mutation. Hormone replacement therapy, family history and oophorectomy were not associated with breast cancer risk., Conclusions: Findings from this large prospective study indicate that the risk of developing breast cancer remains high after age 60 in both BRCA1 and BRCA2 mutation carriers. These findings warrant further evaluation of the role of breast cancer screening in older mutation carriers.

Background: Exome and genome sequencing have been demonstrated to increase diagnostic yield in paediatric populations, improving treatment options and providing risk information for relatives. There are limited studies examining the clinical utility of these tests in adults, who currently have limited access to this technology., Methods: Patients from adult and cancer genetics clinics across Toronto, Ontario, Canada were recruited into a prospective cohort study evaluating the diagnostic utility of exome and genome sequencing in adults. Eligible patients were ≥18 years of age and suspected of having a hereditary disorder but had received previous uninformative genetic test results. In total, we examined the diagnostic utility of exome and genome sequencing in 47 probands and 34 of their relatives who consented to participate and underwent exome or genome sequencing., Results: Overall, 17% (8/47) of probands had a pathogenic or likely pathogenic variant identified in a gene associated with their primary indication for testing. The diagnostic yield for patients with a cancer history was similar to the yield for patients with a non-cancer history (4/18 (22%) vs 4/29 (14%)). An additional 24 probands (51%) had an inconclusive result. Secondary findings were identified in 10 patients (21%); three had medically actionable results., Conclusions: This study lends evidence to the diagnostic utility of exome or genome sequencing in an undiagnosed adult population. The significant increase in diagnostic yield warrants the use of this technology. The identification and communication of secondary findings may provide added value when using this testing modality as a first-line test., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)