Early cancer diagnoses through BRCA1/2 screening of unselected adult biobank participants

Abstract

PurposeThe clinical utility of screening unselected individuals for pathogenic BRCA1/2 variants has not been established. Data on cancer risk management behaviors and diagnoses of BRCA1/2-associated cancers can help inform assessments of clinical utility.MethodsWhole-exome sequences of participants in the MyCode Community Health Initiative were reviewed for pathogenic/likely pathogenic BRCA1/2 variants. Clinically confirmed variants were disclosed to patient–participants and their clinicians. We queried patient–participants’ electronic health records for BRCA1/2-associated cancer diagnoses and risk management that occurred within 12 months after results disclosure, and calculated the percentage of patient–participants of eligible age who had begun risk management.ResultsThirty-seven MyCode patient–participants were unaware of their pathogenic/likely pathogenic BRCA1/2 variant, had not had a BRCA1/2-associated cancer, and had 12 months of follow-up. Of the 33 who were of an age to begin BRCA1/2-associated risk management, 26 (79%) had performed at least one such procedure. Three were diagnosed with an early-stage, BRCA1/2-associated cancer—including a stage 1C fallopian tube cancer—via these procedures.ConclusionScreening for pathogenic BRCA1/2 variants among unselected individuals can lead to occult cancer detection shortly after disclosure. Comprehensive outcomes data generated within our learning healthcare system will aid in determining whether population-wide BRCA1/2 genomic screening programs offer clinical utility.

Whole exome sequencing and characterization of coding variation in 49,960 individuals in the UK Biobank

“…As an example, we evaluated the risk of cancer in individuals carrying pathogenic variants in BRCA1 or BRCA2 (Figure 3b) to compare across five previously implicated BRCA1/2 associated cancers 23 as well as to explore whether risk was conferred for other cancers. While BRCA1 and BRCA2 have differences in mechanism and risk among cancer subtypes, due to low sample sizes, we analyzed summed counts in 114 males and 110 females with BRCA1/2 reported pathogenic and likely pathogenic variants.…”

Personalized Medicine and the Power of Electronic Health Records

“…Genomic results are clinically confirmed and then deposited into the EHR. By returning genomic results to MyCode participants and following their outcomes, investigators are gaining knowledge about the clinical utility of performing population genomic screening for preventive health (Buchanan et al, 2018). The opportunity for a single test to screen for many diseases at once poses challenges for evaluating its appropriate clinical utility and cost effectiveness.…”

Genome‐wide association studies and polygenic risk scores for skin cancer: clinically useful yet?

“…PRS have been employed across a wide variety of diseases for clinical applications including screening, diagnosis, prognosis and treatment response. Translation of PRS to the clinical setting is being facilitated by large biobanking efforts and large population‐based genotyping, and PRS for breast and prostate cancer have demonstrated clinical utility. While PRS are not currently clinically available for cutaneous carcinomas, research has significantly increased our understanding of genetic susceptibility to cutaneous cancers.…”