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

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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, Peter A; Yadav, Siddhartha; Hu, Chunling; Wunderle, Marius; Häberle, Lothar; Hart, Steven N; Rübner, Matthias; Polley, Eric C; Lee, Kun Y; Gnanaolivu, Rohan D; Hadji, Peyman; Hübner, Hanna; Tesch, Hans; Ettl, Johannes; Overkamp, Friedrich; Lux, Michael P; Ekici, Arif B; Volz, Bernhard; Uhrig, Sabrina; Lüftner, Diana; Wallwiener, Markus; Müller, Volkmar; Belleville, Erik; Untch, Michael; Kolberg, Hans-Christian; Beckmann, Matthias W; Reis, André; Hartmann, Arndt; Janni, Wolfgang; Wimberger, Pauline; Taran, Florin-Andrei; Fehm, Tanja N; Wallwiener, Diethelm; Brucker, Sara Y; Schneeweiss, Andreas; Hartkopf, Andreas D; Couch, Fergus J.

In: J CLIN ONCOL, Vol. 39, No. 15, 20.05.2021, p. 1619-1630.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Fasching, PA, 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, H-C, Beckmann, MW, Reis, A, Hartmann, A, Janni, W, Wimberger, P, Taran, F-A, Fehm, TN, Wallwiener, D, Brucker, SY, Schneeweiss, A, Hartkopf, AD & Couch, FJ 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', J CLIN ONCOL, vol. 39, no. 15, pp. 1619-1630. https://doi.org/10.1200/JCO.20.01200

APA

Fasching, P. A., Yadav, S., Hu, C., Wunderle, M., Häberle, L., Hart, S. N., Rübner, M., Polley, E. C., Lee, K. Y., Gnanaolivu, R. D., Hadji, P., Hübner, H., Tesch, H., Ettl, J., Overkamp, F., Lux, M. P., Ekici, A. B., Volz, B., Uhrig, S., ... 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. J CLIN ONCOL, 39(15), 1619-1630. https://doi.org/10.1200/JCO.20.01200

Vancouver

Fasching PA, Yadav S, Hu C, Wunderle M, Häberle L, Hart SN 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. J CLIN ONCOL. 2021 May 20;39(15):1619-1630. https://doi.org/10.1200/JCO.20.01200

Bibtex

@article{563cbd5fe3fd4675a99501bb87050408,
title = "Mutations in BRCA1/2 and Other Panel Genes in Patients With Metastatic Breast Cancer - Association With Patient and Disease Characteristics and Effect on Prognosis",
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.",
author = "Fasching, {Peter A} and Siddhartha Yadav and Chunling Hu and Marius Wunderle and Lothar H{\"a}berle and Hart, {Steven N} and Matthias R{\"u}bner and Polley, {Eric C} and Lee, {Kun Y} and Gnanaolivu, {Rohan D} and Peyman Hadji and Hanna H{\"u}bner and Hans Tesch and Johannes Ettl and Friedrich Overkamp and Lux, {Michael P} and Ekici, {Arif B} and Bernhard Volz and Sabrina Uhrig and Diana L{\"u}ftner and Markus Wallwiener and Volkmar M{\"u}ller and Erik Belleville and Michael Untch and Hans-Christian Kolberg and Beckmann, {Matthias W} and Andr{\'e} Reis and Arndt Hartmann and Wolfgang Janni and Pauline Wimberger and Florin-Andrei Taran and Fehm, {Tanja N} and Diethelm Wallwiener and Brucker, {Sara Y} and Andreas Schneeweiss and Hartkopf, {Andreas D} and Couch, {Fergus J}",
year = "2021",
month = may,
day = "20",
doi = "10.1200/JCO.20.01200",
language = "English",
volume = "39",
pages = "1619--1630",
journal = "J CLIN ONCOL",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "15",

}

RIS

TY - JOUR

T1 - Mutations in BRCA1/2 and Other Panel Genes in Patients With Metastatic Breast Cancer - Association With Patient and Disease Characteristics and Effect on Prognosis

AU - Fasching, Peter A

AU - Yadav, Siddhartha

AU - Hu, Chunling

AU - Wunderle, Marius

AU - Häberle, Lothar

AU - Hart, Steven N

AU - Rübner, Matthias

AU - Polley, Eric C

AU - Lee, Kun Y

AU - Gnanaolivu, Rohan D

AU - Hadji, Peyman

AU - Hübner, Hanna

AU - Tesch, Hans

AU - Ettl, Johannes

AU - Overkamp, Friedrich

AU - Lux, Michael P

AU - Ekici, Arif B

AU - Volz, Bernhard

AU - Uhrig, Sabrina

AU - Lüftner, Diana

AU - Wallwiener, Markus

AU - Müller, Volkmar

AU - Belleville, Erik

AU - Untch, Michael

AU - Kolberg, Hans-Christian

AU - Beckmann, Matthias W

AU - Reis, André

AU - Hartmann, Arndt

AU - Janni, Wolfgang

AU - Wimberger, Pauline

AU - Taran, Florin-Andrei

AU - Fehm, Tanja N

AU - Wallwiener, Diethelm

AU - Brucker, Sara Y

AU - Schneeweiss, Andreas

AU - Hartkopf, Andreas D

AU - Couch, Fergus J

PY - 2021/5/20

Y1 - 2021/5/20

N2 - 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.

AB - 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.

U2 - 10.1200/JCO.20.01200

DO - 10.1200/JCO.20.01200

M3 - SCORING: Journal article

C2 - 33780288

VL - 39

SP - 1619

EP - 1630

JO - J CLIN ONCOL

JF - J CLIN ONCOL

SN - 0732-183X

IS - 15

ER -