Personalized early detection and prevention of breast cancer: ENVISION consensus statement

Abstract: The European Collaborative on Personalized Early Detection and Prevention of Breast Cancer (ENVISION) brings together several international research consortia working on different aspects of the personalized early detection and prevention of breast cancer. In a consensus conference held in 2019, the members of this network identified research areas requiring development to enable evidence-based personalized interventions that might improve the benefits and reduce the harms of existing breast cancer screening and prevention programmes. The priority areas identified were: 1) breast cancer subtype-specific risk assessment tools applicable to women of all ancestries; 2) intermediate surrogate markers of response to preventive measures; 3) novel non-surgical preventive measures to reduce the incidence of breast cancer of poor prognosis; and 4) hybrid effectiveness–implementation research combined with modelling studies to evaluate the long-term population outcomes of risk-based early detection strategies. The implementation of such programmes would require health-care systems to be open to learning and adapting, the engagement of a diverse range of stakeholders and tailoring to societal norms and values, while also addressing the ethical and legal issues. In this Consensus Statement, we discuss the current state of breast cancer risk prediction, risk-stratified prevention and early detection strategies, and their implementation. Throughout, we highlight priorities for advancing each of these areas

Is there evidence that we should screen the general population for Lynch syndrome with genetic testing? A systematic review

Anya E R Prince,1 R Jean Cadigan,1,2 Gail E Henderson,1,2 James P Evans,1,3–6 Michael Adams,1,3 Emmanuel Coker-Schwimmer,7 Dolly C Penn,2 Marcia Van Riper,1,8 Giselle Corbie-Smith,1,2,6 Daniel E Jonas1,6,7 1Center for Genomics and Society, 2Department of Social Medicine, 3Department of Genetics, 4Carolina Center for Genome Sciences, 5Lineberger Comprehensive Cancer Center, 6Department of Medicine, 7Cecil G. Sheps Center for Health Services Research, 8School of Nursing, The University of North Carolina-Chapel Hill, Chapel Hill, NC, USA Background: The emerging dual imperatives of personalized medicine and technologic advances make population screening for preventable conditions resulting from genetic alterations a realistic possibility. Lynch syndrome is a potential screening target due to its prevalence, penetrance, and the availability of well-established, preventive interventions. However, while population screening may lower incidence of preventable conditions, implementation without evidence may lead to unintentional harms. We examined the literature to determine whether evidence exists that screening for Lynch-associated mismatch repair (MMR) gene mutations leads to improved overall survival, cancer-specific survival, or quality of life. Documenting evidence and gaps is critical to implementing genomic approaches in public health and guiding future research.Materials and methods: Our 2014–2015 systematic review identified studies comparing screening with no screening in the general population, and controlled studies assessing analytic validity of targeted next-generation sequencing, and benefits or harms of interventions or screening. We conducted meta-analyses for the association between early or more frequent colonoscopies and health outcomes.Results: Twelve studies met our eligibility criteria. No adequate evidence directly addressed the main question or the harms of screening in the general population. Meta-analyses found relative reductions of 68% for colorectal cancer incidence (relative risk: 0.32, 95% confidence interval: 0.23–0.43, three cohort studies, 590 participants) and 78% for all-cause mortality (relative risk: 0.22, 95% confidence interval: 0.09–0.56, three cohort studies, 590 participants) for early or more frequent colonoscopies among family members of people with cancer who also had an associated MMR gene mutation.Conclusion: Inadequate evidence exists examining harms and benefits of population-based screening for Lynch syndrome. Lack of evidence highlights the need for data that directly compare benefits and harms. Keywords: Lynch syndrome, systematic review, targeted next-generation sequencing, genetic screening, general populatio

Addressing underrepresentation in genomics research through community engagement.

The vision of the American Society of Human Genetics (ASHG) is that people everywhere will realize the benefits of human genetics and genomics. Implicit in that vision is the importance of ensuring that the benefits of human genetics and genomics research are realized in ways that minimize harms and maximize benefits, a goal that can only be achieved through focused efforts to address health inequities and increase the representation of underrepresented communities in genetics and genomics research. This guidance is intended to advance community engagement as an approach that can be used across the research lifecycle. Community engagement uniquely offers researchers in human genetics and genomics an opportunity to pursue that vision successfully, including by addressing underrepresentation in genomics research

The Genetic Discrimination Observatory: confronting novel issues in genetic discrimination

Genetic discrimination (GD) is the differential or unfair profiling of an individual on the basis of genetic data. This article summarizes the actions of the Genetic Discrimination Observatory (GDO) in addressing GD and recent developments in GD since late 2020. It shows how GD can take many forms in today's rapidly evolving society