Population Based Testing for Primary Prevention: A Systematic Review

Abstract

The current clinical model for genetic testing is based on clinical-criteria/family-history (FH) and a pre-defined mutation probability threshold. It requires people to develop cancer before identifying unaffected individuals in the family to target prevention. This process is inefficient, resource intensive and misses >50% of individuals or mutation carriers at risk. Population genetic-testing can overcome these limitations. It is technically feasible to test populations on a large scale; genetic-testing costs are falling and acceptability and awareness are rising. MEDLINE, EMBASE, Pubmed, CINAHL and PsychINFO databases were searched using free-text and MeSH terms; retrieved reference lists of publications were screened; additionally, web-based platforms, Google, and clinical-trial registries were searched. Quality of studies was evaluated using appropriate check-lists. A number of studies have evaluated population-based BRCA-testing in the Jewish population. This has been found to be acceptable, feasible, clinically-effective, safe, associated with high satisfaction rates and extremely cost-effective. Data support change in guidelines for population-based BRCA-testing in the Jewish population. Population panel testing for BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 gene mutations is the most cost-effective genetic-testing strategy in general-population women and can prevent thousands more breast and ovarian cancers than current clinical-criteria based approaches. A few ongoing studies are evaluating population-based genetic-testing for multiple cancer susceptibility genes in the general population but more implementation studies are needed. A future population-testing programme could also target other chronic diseases.

Healthcare Utilization and Costs after Receiving a Positive BRCA1/2 Result from a Genomic Screening Program

“…An important role of BRCA1/2 testing is to identify high-risk variant carriers before they develop breast or ovarian cancer, so they may start cancer screening and preventive interventions to reduce cancer risk. However, evidence shows that current clinical genetic testing practice, which is primarily based on family history criteria and a predefined mutation probability threshold, is inefficient, resource-intensive, and misses >50% of individuals or mutation carriers at risk [1,14,30]. In a 2018 systematic review of population-based testing, the authors concluded that large scale general population-based screening can overcome these limitations as genetic-testing costs are falling and acceptability and awareness are increasing, yet there are few large-scale programs for unaffected women and a lack of evidence for their costs and consequences [14].…”

“…However, evidence shows that current clinical genetic testing practice, which is primarily based on family history criteria and a predefined mutation probability threshold, is inefficient, resource-intensive, and misses >50% of individuals or mutation carriers at risk [1,14,30]. In a 2018 systematic review of population-based testing, the authors concluded that large scale general population-based screening can overcome these limitations as genetic-testing costs are falling and acceptability and awareness are increasing, yet there are few large-scale programs for unaffected women and a lack of evidence for their costs and consequences [14]. Despite the positive trend in rates of BRCA1/2 testing, [31] the majority of at-risk women do not get a referral for genetic counseling and testing, and a large majority of BRCA1/2 variant carriers in the US have not been identified [32].…”

“…This study focused on one of the most prevalent and actionable conditions-HBOC, for which there is the support that genomic screening programs may better identify patients at high risk [1,14] compared to current guideline-based methods used to identify BRCA1/2 carriers [7,15,16]. Screening for pathogenic/likely pathogenic (P/LP) variants in HBOC susceptibility genes in unselected individuals can be used to assess risk and guide decision-making about surveillance (MRI/mammogram) and prophylaxis (surgical and chemopreventive) for prevention and early detection of breast and ovarian cancer [17].…”

Hereditary Breast and Ovarian Cancer in Families from Southern Italy (Sicily)—Prevalence and Geographic Distribution of Pathogenic Variants in BRCA1/2 Genes

“…Currently, the most used population model for studying the feasibility and efficacy of the population-based BRCA testing is represented by Jewish population; however, implementation studies are needed for testing multiple cancer susceptibility genes in the general population [29]. Therefore, the current guidelines for genetic testing, based on clinical criteria and family history, could be replaced by new approaches able to detect the 50% more BRCA carriers than those identified by conventional criteria [33,34].…”

Germline <b><i>BRCA</i></b> Mutation Rates in Latina Women Presenting for Gynecologic Oncology Care

“…The presence of a mutation in BRCA1 or BRCA2 increases a woman's breast cancer risk by 6-7-fold; for ovarian cancer, the risk is upward of 30 or 10-fold over baseline, respectively [6][7][8][9][10][11][12][13][14]. Currently, most of genetic testing is carried out based on patient's personal history of cancer or high-risk family history [15]. Populationbased studies have been carried out in the Ashkenazi Jewish/Jewish populations [16][17][18], demonstrating potential feasibility and benefit.…”