@article{54986535067f4feba409c9502173645b,
title = "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.",
keywords = "BRCA1, BRCA2, Hereditary Breast and Ovarian Cancer Syndrome, Whole Exome sequencing, biobank",
author = "Buchanan, {Adam H.} and Kandamurugu Manickam and Meyer, {Michelle N.} and Wagner, {Jennifer K.} and Hallquist, {Miranda L.G.} and Williams, {Janet L.} and Rahm, {Alanna Kulchak} and Williams, {Marc S.} and Chen, {Zong Ming E.} and Shah, {Chaitali K.} and Garg, {Tullika K.} and Lazzeri, {Amanda L.} and Schwartz, {Marci L.B.} and Lindbuchler, {D'andra M.} and Fan, {Audrey L.} and Rosemary Leeming and Servano, {Pedro O.} and Smith, {Ashlee L.} and Vogel, {Victor G.} and Abul-Husn, {Noura S.} and Dewey, {Frederick E.} and Lebo, {Matthew S.} and Mason-Suares, {Heather M.} and Ritchie, {Marylyn D.} and {Daniel Davis}, F. and Carey, {David J.} and Feinberg, {David T.} and {Andrew Faucett}, W. and Ledbetter, {David H.} and Murray, {Michael F.}",
note = "Funding Information: The genomic screening program described here was funded by institutional support from GHS and grants from the Horace W. Goldsmith Foundation, the Mericle Foundation, the Robert Wood Johnson Foundation, and the Commonwealth of Pennsylvania— Department of Community and Economic Development. These funders had no role in study design, collection or analysis of data, or the decision to publish. We are grateful to the more than 150,000 MyCode participants for their participation in this research and, in particular, to the three patient–participants described here for their willingness to share their information. We thank the MyCode leadership, including Carroll Flansburg and Ann Mooney, and the many MyCode consenters, for their thorough patient engagement. We are grateful for the rigor and responsiveness exhibited by bioinformatics colleagues at the Laboratory for Molecular Medicine, particularly Christina Austin-Tse and Heidi Rehm, and at GHS, particularly Raghu Metpally and Thomas Person. Finally, we thank the staff of Geisinger Clinical Genomics and the Inherited Risk Breast Clinic for helping to coordinate care for individuals with a genomic result. Publisher Copyright: {\textcopyright} American College of Medical Genetics and Genomics.",
year = "2018",
month = apr,
day = "1",
doi = "10.1038/gim.2017.145",
language = "English",
volume = "20",
pages = "554--558",
journal = "Genetics in Medicine",
issn = "1098-3600",
publisher = "Elsevier BV",
number = "5",
}