Errors in Germline Biomarker Testing

Purpose: Germline biomarker testing to assess inherited risk for developing malignancy has evolved quickly from testing for 1 or 2 genes from a few laboratories to ordering panels of 80 or more genes available from multiple laboratories. Many health professionals did not receive foundational information in training yet are expected to identify and manage care for individuals and families with germline risk. Errors in testing do occur and can have significant adverse consequences including missed opportunities for prevention and detection for the patient and family, unnecessary risk-reducing surgery, and even death. By better understanding these errors and underlying causes, as well as the potential negative consequences due to these errors, strategies can be developed to help prevent future harm to patients. Methods: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting system a literature review was completed to identify case reports of errors in germline testing for hereditary cancer. Ovid MEDLINE, Scopus, and EBSCOHOST CINAHL, were searched from January 2009 through February 2025. Reference lists were reviewed to identify additional case reports. Each case report was abstracted to identify error(s), consequence(s), and potential error(s) prevented. Results: A total of 106 cases were identified from the search of the databases and 1 case using archival methods. Sixty-six (61%) cases described more than one error and 61 (44%) described more than one negative consequence. In 48 (45%) cases one or more additional errors were prevented when a genetics professional was consulted. The most common errors were misinterpretation of data, failure to take a full family history and review previous test results, not recognizing a syndrome, and selecting the wrong test or wrong laboratory for testing. Negative consequences included missed opportunities for prevention and detection for the patient and potentially other family members, one or more unnecessary risk-reducing surgeries in 10 patients, late detection of malignancy in 8 patients, and 7 patient deaths. Discussion: Although germline testing seems to be a simple laboratory test, many errors occur that have avoidable adverse consequences for both the patient and family. Errors may occur because of a lack of foundational knowledge in comprehensive risk assessment and on how to order the best test in a laboratory capable of detecting a pathogenic variant as well as how to interpret germline testing results. Increasing the number of genetics professionals, implementing new delivery models, and increasing educational efforts in nongenetics professionals could prevent and decrease errors.