Clinical Utility of Universal Germline Genetic Testing for Patients With Breast Cancer

Abstract

ImportanceNational Comprehensive Cancer Network guidelines currently recommend germline testing for high-risk genes in selected patients with breast cancer. The clinical utility of recommending testing all patients with breast cancer with multigene panels is currently under consideration.ObjectiveTo examine the implications of universal testing of patients with breast cancer with respect to clinical decision-making.Design, Setting, and ParticipantsPatients from a previously reported cohort were assessed as in-criteria or out-of-criteria according to the 2017 guidelines and underwent testing with a multigene germline panel between 2017 to 2018. Patients were women and men aged 18 to 90 years, with a new and/or previous diagnosis of breast cancer who had not undergone either single or multigene testing. Clinicians from 20 community and academic sites documented patient clinical information and changes to clinical recommendations made according to test findings. Association between prevalence of pathogenic or likely pathogenic germline variants and previously unreported clinical features, including scores generated by the BRCAPRO statistical model, was determined. Data were analyzed from April 2020 to May 2022.ExposureNew and/or previous diagnosis of breast cancer.Main Outcomes and MeasuresDisease management recommendations that were changed as a result of genetic testing results are reported.ResultsClinicians were asked to assess changes to clinical management as a result of germline genetic testing for 952 patients. Informative clinician-reported recommendations were provided for 939 (467 in-criteria and 472 out-of-criteria) of the patients with breast cancer (936 [99.7%] female; 702 [74.8%] White; mean [SD] age at initial diagnosis, 57.6 [11.5] years). One or more changes were reported for 31 of 37 (83.8%) in-criteria patients and 23 of 34 (67.6%) out-of-criteria patients with a pathogenic or likely pathogenic variant. Recommendations were changed as a result of testing results for 14 of 22 (63.6%) out-of-criteria patients who had a variant in a breast cancer predisposition gene. Clinicians considered testing beneficial for two-thirds of patients with pathogenic or likely pathogenic variants and for one-third of patients with either negative results or variants of uncertain significance. There was no difference in variant rate between patients meeting the BRCAPRO threshold (≥10%) and those who did not (P = .86, Fisher exact test). No changes to clinical recommendations were made for most patients with negative results (345 of 349 patients [98.9%]) or variants of uncertain significance (492 of 509 patients [96.7%]).Conclusions and RelevanceIn this cohort study, germline genetic testing was used by clinicians to direct treatment for most out-of-criteria patients with breast cancer with pathogenic or likely pathogenic germline variants, including those with moderate-risk variants. Universal germline testing informs clinical decision-making and provides access to targeted treatments and clinical trials for all patients with breast cancer.

Universal Germline and Tumor Genomic Testing Needed to Win the War Against Cancer: Genomics Is the Diagnosis

“…In fact, a study showed that testing all patients with breast cancer (versus guideline-based testing) doubles the number of patients identified as having an actionable germline genetic result, 3 consistent with a report suggesting that restrictive testing may deny data-informed clinical management to patients with breast cancer. 4 Even in other cancers with clear testing guidelines such as ovarian, pancreatic, and metastatic prostate cancers, there is significant testing underutilization, perhaps because of the complexity of guidelines between cancers. 5 There is ample evidence that broad-based reflex testing of germline (providing the patient agrees) is necessary for individuals with a cancer diagnosis.…”

Universal genetic testing for women with newly diagnosed breast cancer in the context of multidisciplinary team care

“…In other models, the test result is always delivered by the genetics team 9,10 . However, it has been reported that many people carrying pathogenic variants might be missed were selection for testing to rely solely on the threshold in the current guidelines 11,12 …”

“…9,10 However, it has been reported that many people carrying pathogenic variants might be missed were selection for testing to rely solely on the threshold in the current guidelines. 11,12 Significantly reduced DNA sequencing costs and increased testing capacity raises the possibility of universal germline testing of women with newly diagnosed breast cancer. 11 However, more rapid delivery of results would be required to incorporate them into management.…”

The Evolution of Genetic Testing from Focused Testing to Panel Testing and from Patient Focused to Population Testing: Are We There Yet?

“…21 A large multistate trial of 952 breast cancer patients found that 68.3% of patients who met criteria and 57.5% of those who did not meet criteria who had PGVs had positively impacted health outcomes related to a change in clinical management. 22…”