Mutations in BRCA1/2 and Other Panel Genes in Patients With Metastatic Breast Cancer -Association With Patient and Disease Characteristics and Effect on Prognosis

Fasching P, Yadav S, Hu C, Wunderle M, Häberle L, Hart SN, Rübner M, Polley EC, Lee KY, Gnanaolivu RD, Hadji P, Hübner H, Tesch H, Ettl J, Overkamp F, Lux MP, Ekici AB, Volz B, Uhrig S, Lüftner D, Wallwiener M, Müller V, Belleville E, Untch M, Kolberg HC, Beckmann M, Reis A, Hartmann A, Janni W, Wimberger P, Taran FA, Fehm TN, Wallwiener D, Brucker SY, Schneeweiss A, Hartkopf AD, Couch FJ (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Book Volume: 39

Pages Range: 1619-1630

Journal Issue: 15

DOI: 10.1200/JCO.20.01200

Abstract

PURPOSE: Among patients with metastatic breast cancer (mBC), the frequency of germline mutations in cancer susceptibility genes and the clinical relevance of these mutations are unclear. In this study, a prospective cohort of patients with mBC was used to determine mutation rates for breast cancer (BC) predisposition genes, to evaluate the clinical characteristics of patients with mutations, and to assess the influence of mutations on patient outcome. PATIENTS AND METHODS: Germline DNA from 2,595 patients with mBC enrolled in the prospective PRAEGNANT registry was evaluated for mutations in cancer predisposition genes. The frequencies of mutations in known BC predisposition genes were compared with results from a prospective registry of patients with nonmetastatic BC sequenced using the same QIAseq method and with public reference controls. Associations between mutation status and tumor characteristics, progression-free survival, and overall survival were assessed. RESULTS: Germline mutations in 12 established BC predisposition genes (including BRCA1 and BRCA2) were detected in 271 (10.4%) patients. A mutation in BRCA1 or BRCA2 was seen in 129 patients (5.0%). BRCA1 mutation carriers had a higher proportion of brain metastasis (27.1%) compared with nonmutation carriers (12.8%). Mutations were significantly enriched in PRAEGNANT patients with mBC compared with patients with nonmetastatic BC (10.4% v 6.6%, P < .01). Mutations did not significantly modify progression-free survival or overall survival for patients with mBC. CONCLUSION: Multigene panel testing may be considered in all patients with mBC because of the high frequency of germline mutations in BRCA1/2 and other BC predisposition genes. Although the prognosis of mutation carriers and nonmutation carriers with mBC was similar, differences observed in tumor characteristics have implications for treatment and for future studies of targeted therapies.

Authors with CRIS profile

Involved external institutions

Mayo Clinic United States (USA) (US) St. Josefs-Krankenhaus Salzkotten Germany (DE) Frankfurter Hormon und Osteoporosezentrum Germany (DE) Agaplesion Markus Krankenhaus Germany (DE) Klinikum rechts der Isar Germany (DE) Oncologianova GmbH Germany (DE) Hochschule Ansbach Germany (DE) Charité - Universitätsmedizin Berlin Germany (DE) Ruprecht-Karls-Universität Heidelberg Germany (DE) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) ClinSol GmbH & Co.KG Germany (DE) Marienhospital Bottrop Germany (DE) Universitätsklinikum Ulm Germany (DE) Universitätsklinikum Carl Gustav Carus Dresden Germany (DE) Universitätsklinikum Freiburg Germany (DE) Universitätsklinikum Düsseldorf Germany (DE) Eberhard Karls Universität Tübingen Germany (DE) Universitätsklinikum Heidelberg Germany (DE)

How to cite

APA:

Fasching, P., Yadav, S., Hu, C., Wunderle, M., Häberle, L., Hart, S.N.,... Couch, F.J. (2021). Mutations in BRCA1/2 and Other Panel Genes in Patients With Metastatic Breast Cancer -Association With Patient and Disease Characteristics and Effect on Prognosis. Journal of Clinical Oncology, 39(15), 1619-1630. https://dx.doi.org/10.1200/JCO.20.01200

MLA:

Fasching, Peter, et al. "Mutations in BRCA1/2 and Other Panel Genes in Patients With Metastatic Breast Cancer -Association With Patient and Disease Characteristics and Effect on Prognosis." Journal of Clinical Oncology 39.15 (2021): 1619-1630.

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