No abstract

Cascade screening is the process of contacting relatives of people who have been diagnosed with certain hereditary conditions. Its purpose is to identify, inform, and manage those who are also at risk. We conducted a scoping review to obtain a broad overview of cascade screening interventions, facilitators and barriers to their use, relevant policy considerations, and future research needs. We searched for relevant peer-reviewed literature in the period 1990-2017 and reviewed 122 studies. Finally, we described 45 statutes and regulations related to the use and release of genetic information across the fifty states. We sought standardized best practices for optimizing cascade screening across various geographic and policy contexts, but we found none. Studies in which trained providers contacted relatives directly, rather than through probands (index patients), showed greater cascade screening uptake; however, policies in some states might limit this approach. Major barriers to cascade screening delivery include suboptimal communication between the proband and family and geographic barriers to obtaining genetic services. Few US studies examined interventions for cascade screening or used rigorous study designs such as randomized controlled trials. Moving forward, there remains an urgent need to conduct rigorous intervention studies on cascade screening in diverse US populations, while accounting for state policy considerations.

Although genomic discovery provides the potential for population health benefit, the current knowledge base around implementation to turn this promise into a reality is severely limited. Current gaps in the literature demonstrate a need to apply implementation science principles to genomic medicine in order to deliver on the promise of precision medicine.Genet Med advance online publication 12 January 2017.

We examined the current literature to understand factors that influence endocrine therapy (ET) adherence among racial/ethnic and socioeconomic subpopulations of breast cancer patients. We searched PubMed and PsycINFO databases for studies from January 1, 1978, to June 20, 2014, and January 1, 1991, to June 20, 2014, respectively, and hand-searched articles from relevant literature reviews. We abstracted and synthesized results within a social ecological framework. Fourteen articles met all inclusion criteria. The majority of included articles reported significant underuse of ET among minority and low-income women. Modifiable intrapersonal, interpersonal, and community-level factors are associated with ET use, and these factors vary across subgroups. Both race/ethnicity and socioeconomic status are associated with ET use in most settings. Variation in factors associated with ET use across subgroups indicates the need for more nuanced research and targeted interventions among breast cancer patients.

Over the past decade, genome-wide association studies have identified genetic variation associated with a wide range of human diseases and traits. These findings are now commonly aggregated into polygenic risk scores, which can bridge the gap between the initial discovery efforts and clinical applications for disease risk estimation. However, there is remarkable heterogeneity in the reporting of these risk scores due to a lack of accepted standards for the development, reporting, and application of PRS. This lack of rigorous standards hinders the translation of PRS into clinical care. The ClinGen Complex Disease Working Group, in a collaboration with the Polygenic Score (PGS) Catalog, have developed a novel PRS Reporting Statement (PRS-RS), updating previous standards to the current state of the field. Drawing upon experts in epidemiology, statistics, disease-specific applications, implementation, and policy, this 33-item reporting framework defines the minimal information needed to interpret and evaluate a PRS, especially with respect to any downstream clinical applications. Items span detailed descriptions of the study population (recruitment method, key demographics, inclusion/exclusion criteria, and phenotype definition), statistical methods for both PRS development and validation, and considerations for potential limitations of the published risk score and downstream clinical utility. Additionally, emphasis has been placed on data availability and transparency to facilitate reproducibility and benchmarking against other PRS, such as deposition in the publicly available PGS Catalog. By providing these criteria in a structured format that borrows from existing standards and ontologies, the use of this framework in publishing PRS will facilitate PRS translation into clinical care and progress towards defining best practices.

Overall, 5-year BCSS is excellent for patients with RS < 18 and micrometastases, one or two positive lymph nodes, and worsens with additionally involved lymph nodes. Further analyses should account for treatment variables, and longitudinal updates will be important to better characterize utilization of Oncotype DX testing and long-term survival outcomes.

Novel phase I oncology trial designs may attract patients with less constrained treatment options, but the inclusion of targeted drugs and combinations including standard chemotherapies is likely to complicate understanding of safety and dosing objectives and likelihood of personal benefit for purposes of informed consent.

Purpose Oncotype DX (ODX) is a tumor gene-profiling test that aids in adjuvant chemotherapy decision-making. ODX has the potential to improve quality of care; however, if not equally accessible across racial groups, disparities in cancer care quality may persist or worsen. We examined racial disparities in ODX testing uptake. Methods We used data from the Carolina Breast Cancer Study, phase III, a longitudinal, population-based study of 2,998 North Carolina women who received a diagnosis of breast cancer between 2008 and 2014. Our primary analysis used modified Poisson regression to determine the association between race and whether ODX testing was ordered among two strata: node-negative and node-positive breast cancer. Results A total of 1,468 women with estrogen receptor–positive, human epidermal growth factor receptor-2–negative, stage I or II breast cancer met inclusion criteria. Black patients had higher-grade and larger tumors, more comorbidities, younger age at diagnosis, and lower socioeconomic status than non-black women. Overall, 42% of women had ODX test results in their pathology reports. Compared with those who did not receive ODX testing, women who received ODX testing tended to be younger and have medium tumor size and grade. Our regression analyses indicated no racial disparities in ODX uptake among node-negative patients. However, racial differences were detected among node-positive patients, with black patients being 46% less likely to receive ODX testing than non-black women (adjusted relative risk, 0.54; 95% CI, 0.35 to 0.84; P = .006). Conclusion We did not find racial disparities in ODX testing for node-negative patients for whom ODX testing is guideline recommended and widely covered by insurers. However, our findings suggest that a newer, non–guideline-concordant application of ODX testing for node-positive breast cancer was accessed less by black women than by non-black women, reflecting more guideline concordant care among black women.