Genetics Adviser: The development and usability testing of a new patient digital health application to support clinical genomic testing.

Purpose: Increasing demand for genomic testing coupled with genetics workforce shortages has placed unsustainable pressure on standard models of care. Digital tools can offer improved access, efficiency, and cost savings. We created a patient-facing digital health application to support genomic testing.

Opportunistic genomic screening has clinical utility: An interventional cohort study.

Purpose: Practice is shifting toward genome-first approaches, such as opportunistic screening for secondary findings (SFs). Analysis of SFs could be extended beyond medically actionable results to include non-medically actionable monogenic disease risks, carrier status, pharmacogenomic variants, and risk variants for common complex disease. However, evidence on the clinical utility of returning these results is lacking.

Incidence of peritoneal cancer after oophorectomy among BRCA1 and BRCA2 mutation carriers.

Background: To estimate the incidence of primary peritoneal cancer after preventive bilateral oophorectomy in women with a BRCA1 or BRCA2 mutation.

Methods: A total of 6310 women with a BRCA1 or BRCA2 mutation who underwent a preventive bilateral oophorectomy were followed for a mean of 7.8 years from oophorectomy.

The risk of skin cancer in women who carry BRCA1 or BRCA2 mutations.

Background: It has not been clearly established if skin cancer or melanoma are manifestations of BRCA1 or BRCA2 mutation carrier status. Estimating the risk of skin cancer is an important step towards developing screening recommendations.

Methods: We report the findings of a prospective cohort study of 6,207 women from North America who carry BRCA1 or BRCA2 mutations.

BRCA1 frameshift variants leading to extended incorrect protein C termini.

Carriers of BRCA1 germline pathogenic variants are at substantially higher risk of developing breast and ovarian cancer than the general population. Accurate identification of at-risk individuals is crucial for risk stratification and the implementation of targeted preventive and therapeutic interventions. Despite significant progress in variant classification efforts, a sizable portion of reported BRCA1 variants remain as variants of uncertain clinical significance (VUSs).

Theory-based behavior change intervention to increase uptake of risk-reducing salpingo-oophorectomy in women with a BRCA1 or BRCA2 pathogenic variant: The PREVENT randomized controlled trial.

Objective: To evaluate the effect of a theory-based behavioral intervention delivered by genetic counselors on the uptake of risk-reducing salpingo-oophorectomy (RRSO) at 12 and 24 months by women with a BRCA1 or BRCA2 pathogenic variant (PV) compared to women who received usual care.

Methods: In this two-arm, multi-site randomized controlled trial participants were randomized to receive a theoretically-guided behavioral telephone intervention or usual care. Outcome data were collected at 12 and 24 months.

Vitamin D and Calcium Supplement Use and High-Risk Breast Cancer: A Case-Control Study among and Mutation Carriers.

The role of vitamin D and calcium use in the development of breast cancer among women in the general population is not clear. Furthermore, whether vitamin D and calcium supplement use are associated with breast cancer in high-risk populations has not been evaluated. Thus, we evaluated the association between vitamin D and/or calcium supplement use and breast cancer among women with a pathogenic variant (mutation) in or .

A comprehensive genomic reporting structure for communicating all clinically significant primary and secondary findings.

Genomic sequencing (GS) can reveal secondary findings (SFs), findings unrelated to the reason for testing, that can be overwhelming to both patients and providers. An effective approach for communicating all clinically significant primary and secondary GS results is needed to effectively manage this large volume of results. The aim of this study was to develop a comprehensive approach to communicate all clinically significant primary and SF results.

Genetics Adviser: a protocol for a mixed-methods randomised controlled trial evaluating a digital platform for genetics service delivery.

Introduction: The high demand for genetic tests and limited supply of genetics professionals has created a need for alternative service delivery models. Digital tools are increasingly being used to support multiple points in the genetic testing journey; however, none are transferable across multiple clinical specialties and settings nor do they encompass the entire trajectory of the journey. We aim to evaluate the effectiveness of the Genetics Adviser, an interactive, patient-facing, online digital health tool that delivers pre-test counselling, provides support during the waiting period for results, and returns results with post-test counselling, encompassing the entire patient genetic testing journey.

Impact of rapid genetic testing for BRCA1 and BRCA2 at time of breast cancer diagnosis on psychosocial functioning.

Purpose: Many women are being offered rapid genetic testing (RGT) for cancer predisposition genes, at the time of breast cancer diagnosis prior to surgery. The goal of this study was to determine if psychosocial functioning was affected in women receiving RGT for BRCA1 and BRCA2 at the time of breast cancer diagnosis.

Methods: Participants were women with invasive breast cancer diagnosed between 2013 and 2018, at four centres in Toronto, Canada.

Weight Gain and the Risk of Ovarian Cancer in and Mutation Carriers.

Background: Weight gain and other anthropometric measures on the risk of ovarian cancer for women with mutations are not known. We conducted a prospective analysis of weight change since age 18, height, body mass index (BMI) at age 18, and current BMI and the risk of developing ovarian cancer among and mutation carriers.

Methods: In this prospective cohort study, height, weight, and weight at age 18 were collected at study enrollment.

Incidental findings from cancer next generation sequencing panels.

Next-generation sequencing (NGS) technologies have facilitated multi-gene panel (MGP) testing to detect germline DNA variants in hereditary cancer patients. This sensitive technique can uncover unexpected, non-germline incidental findings indicative of mosaicism, clonal hematopoiesis (CH), or hematologic malignancies. A retrospective chart review was conducted to identify cases of incidental findings from NGS-MGP testing.

An evaluation of memory and attention in BRCA mutation carriers using an online cognitive assessment tool.

Background: The objective of this study was to evaluate the impact of various surgical, hormonal, and lifestyle factors on memory and attention in women with a BRCA1 or BRCA2 mutation.

Methods: BRCA mutation carriers enrolled in a longitudinal study were invited to complete an online brain health assessment tool designed to screen for cognitive deficits. Four measures of memory and executive attention were assessed individually, and an overall score was compiled adjusting for age.

A Comparison of Patient-Reported Outcomes Following Consent for Genetic Testing Using an Oncologist- or Genetic Counselor-Mediated Model of Care.

This study compares knowledge, experience and understanding of genetic testing, and psychological outcomes among breast and ovarian cancer patients undergoing multi-gene panel testing via genetic counselor-mediated (GMT) or oncologist-mediated (OMT) testing models. A pragmatic, prospective survey of breast and ovarian cancer patients pursuing genetic testing between January 2017 and August 2019 was conducted at the Princess Margaret Cancer Centre in Toronto, Canada. A total of 120 (80 GMT; 40 OMT) individuals completed a survey administered one week following consent to genetic testing.

The Prevent Ovarian Cancer Program (POCP): Identification of women at risk for ovarian cancer using complementary recruitment approaches.

Background: Up to 20% of high-grade serous ovarian carcinomas (HGSOC) are hereditary; however, historical uptake of genetic testing is low. We used a unique combination of approaches to identify women in Ontario, Canada, with a first-degree relative (FDR) who died from HGSOC without prior genetic testing, and offer them multi-gene panel testing.

Methods: From May 2015-Sept 2019, genetic counseling and testing was provided to eligible participants.

Tumor surveillance for children and adolescents with cancer predisposition syndromes: The psychosocial impact reported by adolescents and caregivers.

Purpose: Individuals with cancer predisposition syndromes (CPS) are often followed in cancer screening programs, which aim to detect early stage tumors. While cancer surveillance has the potential to improve patient outcomes, its psychosocial impact is uncharacterized in the pediatric population. We examined the cancer surveillance experience from the perspectives of adolescents and parents of children at risk of developing cancer.

Risk and protective factors for intention of contraception use among women in Ghana.

The use of various forms of contraception in Ghana gained prominence after the government resorted to investing more in family planning programs when maternal mortality was declared an emergency in the country. In Ghana, the intention to use and actual usage of contraceptives is influenced by many factors, which may lead to non-usage or discontinuation. This quantitative study was conducted to determine risk and protective factors impacting on the intention and usage of contraceptives.

The relationship between the predicted risk of death and psychosocial functioning among women with early-stage breast cancer.

Purpose: Many women with early-onset breast cancer experience adverse psychological sequelae which impact on their quality of life. We sought to correlate levels of anxiety and cancer-related distress in women with breast cancer shortly after surgery and one year after treatment with the estimated risk of death.

Methods: We studied 596 women with Stage I to III breast cancer.

Setting a baseline: A 7-year review of referral rates and outcomes for serous ovarian cancer prior to implementation of oncologist mediated genetic testing.

Objective: Despite guidelines recommending that all women with invasive serous ovarian cancer (SOC) are offered genetic testing, published referral and testing rates have been poor. Many centers have implemented novel genetic counseling service delivery models to increase testing rates. In light of increased awareness and implementation of small process changes at our center, this study aims to establish baseline referral rates and testing outcomes prior to diverging from the traditional model of care.

Health outcomes, utility and costs of returning incidental results from genomic sequencing in a Canadian cancer population: protocol for a mixed-methods randomised controlled trial.

Introduction: Genomic sequencing has rapidly transitioned into clinical practice, improving diagnosis and treatment options for patients with hereditary disorders. However, large-scale implementation of genomic sequencing faces challenges, especially with regard to the return of incidental results, which refer to genetic variants uncovered during testing that are unrelated to the primary disease under investigation, but of potential clinical significance. High-quality evidence evaluating health outcomes and costs of receiving incidental results is critical for the adoption of genomic sequencing into clinical care and to understand the unintended consequences of adoption of genomic sequencing.

International trends in the uptake of cancer risk reduction strategies in women with a BRCA1 or BRCA2 mutation.

Background: Women with a BRCA1 or BRCA2 mutation face high risks of breast and ovarian cancer. In the current study, we report on uptake of cancer screening and risk-reduction options in a cohort of BRCA mutation carriers from ten countries over two time periods (1995 to 2008 and 2009 to 2017).

Methods: Eligible subjects were identified from an international database of female BRCA mutation carriers and included women from 59 centres from ten countries.

Oophorectomy and risk of contralateral breast cancer among BRCA1 and BRCA2 mutation carriers.

Purpose: Following a diagnosis of breast cancer, BRCA mutation carriers face an increased risk of developing a second (contralateral) cancer in the unaffected breast. It is important to identify predictors of contralateral cancer in order to make informed decisions about bilateral mastectomy. The impact of bilateral salpingo-oophorectomy (i.

Folic acid supplement use and breast cancer risk in BRCA1 and BRCA2 mutation carriers: a case-control study.

Purpose: Supplemental folic acid (the more bioavailable and synthetic form of folate) and breast cancer risk in BRCA mutation carriers have not been studied. We evaluated folic acid, vitamin B6 and vitamin B12 supplement use, and breast cancer risk among BRCA mutation carriers.

Methods: In this case-control study, dietary supplement use was collected from BRCA mutation carriers living in Canada.