Susceptibility gene mutations in germline and tumors of patients with HER2-negative advanced breast cancer

  1. Fasching, Peter A. ORCID logo
  2. Hu, Chunling
  3. Hart, Steven ORCID logo
  4. Ruebner, Matthias
  5. Polley, Eric C.
  6. Gnanaolivu, Rohan D.
  7. Hartkopf, Andreas D.
  8. Huebner, Hanna ORCID logo
  9. Janni, Wolfgang
  10. Hadji, Peyman
  11. Tesch, Hans
  12. Uhrig, Sabrina
  13. Ettl, Johannes
  14. Lux, Michael P.
  15. Lüftner, Diana
  16. Wallwiener, Markus
  17. Wurmthaler, Lena A.
  18. Goossens, Chloë
  19. Müller, Volkmar
  20. Beckmann, Matthias W.
  21. Hein, Alexander ORCID logo
  22. Anetsberger, Daniel
  23. Belleville, Erik
  24. Wimberger, Pauline
  25. Untch, Michael
  26. Ekici, Arif ORCID logo
  27. Kolberg, Hans-Christian
  28. Hartmann, Arndt
  29. Taran, Florin-Andrei
  30. neubauer, hans ORCID logo
  31. Wallwiener, Diethelm
  32. Brucker, Sara Y.
  33. Schneeweiss, Andreas
  34. Häberle, Lothar
  35. Couch, Fergus J.

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1000 Titel
  • Susceptibility gene mutations in germline and tumors of patients with HER2-negative advanced breast cancer
1000 Autor/in
  1. Fasching, Peter A. |
  2. Hu, Chunling |
  3. Hart, Steven |
  4. Ruebner, Matthias |
  5. Polley, Eric C. |
  6. Gnanaolivu, Rohan D. |
  7. Hartkopf, Andreas D. |
  8. Huebner, Hanna |
  9. Janni, Wolfgang |
  10. Hadji, Peyman |
  11. Tesch, Hans |
  12. Uhrig, Sabrina |
  13. Ettl, Johannes |
  14. Lux, Michael P. |
  15. Lüftner, Diana |
  16. Wallwiener, Markus |
  17. Wurmthaler, Lena A. |
  18. Goossens, Chloë |
  19. Müller, Volkmar |
  20. Beckmann, Matthias W. |
  21. Hein, Alexander |
  22. Anetsberger, Daniel |
  23. Belleville, Erik |
  24. Wimberger, Pauline |
  25. Untch, Michael |
  26. Ekici, Arif |
  27. Kolberg, Hans-Christian |
  28. Hartmann, Arndt |
  29. Taran, Florin-Andrei |
  30. neubauer, hans |
  31. Wallwiener, Diethelm |
  32. Brucker, Sara Y. |
  33. Schneeweiss, Andreas |
  34. Häberle, Lothar |
  35. Couch, Fergus J. |
1000 Verlag Nature Publishing Group UK
1000 Erscheinungsjahr 2024
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2024-07-13
1000 Erschienen in
1000 Quellenangabe
  • 10(1):57
1000 Copyrightjahr
  • 2024
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1038/s41523-024-00667-x |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11246424/ |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • <jats:title>Abstract</jats:title><jats:p>Germline mutations in <jats:italic>BRCA1</jats:italic> and <jats:italic>BRCA2</jats:italic> (g<jats:italic>BRCA1/2</jats:italic>) are required for a PARP inhibitor therapy in patients with HER2-negative (HER2−) advanced breast cancer (aBC). However, little is known about the prognostic impact of <jats:italic>gBRCA1/2</jats:italic> mutations in aBC patients treated with chemotherapy. This study aimed to investigate the frequencies and prognosis of germline and somatic <jats:italic>BRCA1/2</jats:italic> mutations in HER2- aBC patients receiving the first chemotherapy in the advanced setting. Patients receiving their first chemotherapy for HER2- aBC were retrospectively selected from the prospective PRAEGNANT registry (NCT02338167). Genotyping of 26 cancer predisposition genes was performed with germline DNA of 471 patients and somatic tumor DNA of 94 patients. Mutation frequencies, progression-free and overall survival (PFS, OS) according to germline mutation status were assessed. g<jats:italic>BRCA1/2</jats:italic> mutations were present in 23 patients (4.9%), and 33 patients (7.0%) had mutations in other cancer risk genes. Patients with a g<jats:italic>BRCA1/2</jats:italic> mutation had a better OS compared to non-mutation carriers (HR: 0.38; 95%CI: 0.17–0.86). PFS comparison was not statistically significant. Mutations in other risk genes did not affect prognosis. Two somatic <jats:italic>BRCA2</jats:italic> mutations were found in 94 patients without <jats:italic>gBRCA1/2</jats:italic> mutations. Most frequently somatic mutated genes were <jats:italic>TP53</jats:italic> (44.7%), <jats:italic>CDH1</jats:italic> (10.6%) and <jats:italic>PTEN</jats:italic> (6.4%). In conclusion, aBC patients with g<jats:italic>BRCA1/2</jats:italic> mutations had a more favorable prognosis under chemotherapy compared to non-mutation carriers. The mutation frequency of ~5% with g<jats:italic>BRCA1/2</jats:italic> mutations together with improved outcome indicates that germline genotyping of all metastatic patients for whom a PARP inhibitor therapy is indicated should be considered.</jats:p>
1000 Sacherschließung
lokal Article
lokal /692/4028/67/1347
lokal article
lokal /692/4028/67/68
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://orcid.org/0000-0003-4885-8471|https://frl.publisso.de/adhoc/uri/SHUsIENodW5saW5n|https://orcid.org/0000-0001-7714-2734|https://frl.publisso.de/adhoc/uri/UnVlYm5lciwgTWF0dGhpYXM=|https://frl.publisso.de/adhoc/uri/UG9sbGV5LCBFcmljIEMu|https://frl.publisso.de/adhoc/uri/R25hbmFvbGl2dSwgUm9oYW4gRC4=|https://frl.publisso.de/adhoc/uri/SGFydGtvcGYsIEFuZHJlYXMgRC4=|https://orcid.org/0000-0001-6889-1493|https://frl.publisso.de/adhoc/uri/SmFubmksIFdvbGZnYW5n|https://frl.publisso.de/adhoc/uri/SGFkamksIFBleW1hbg==|https://frl.publisso.de/adhoc/uri/VGVzY2gsIEhhbnM=|https://frl.publisso.de/adhoc/uri/VWhyaWcsIFNhYnJpbmE=|https://frl.publisso.de/adhoc/uri/RXR0bCwgSm9oYW5uZXM=|https://frl.publisso.de/adhoc/uri/THV4LCBNaWNoYWVsIFAu|https://frl.publisso.de/adhoc/uri/TMO8ZnRuZXIsIERpYW5h|https://frl.publisso.de/adhoc/uri/V2FsbHdpZW5lciwgTWFya3Vz|https://frl.publisso.de/adhoc/uri/V3VybXRoYWxlciwgTGVuYSBBLg==|https://frl.publisso.de/adhoc/uri/R29vc3NlbnMsIENobG-Dqw==|https://frl.publisso.de/adhoc/uri/TcO8bGxlciwgVm9sa21hcg==|https://frl.publisso.de/adhoc/uri/QmVja21hbm4sIE1hdHRoaWFzIFcu|https://orcid.org/0000-0003-2601-3398|https://frl.publisso.de/adhoc/uri/QW5ldHNiZXJnZXIsIERhbmllbA==|https://frl.publisso.de/adhoc/uri/QmVsbGV2aWxsZSwgRXJpaw==|https://frl.publisso.de/adhoc/uri/V2ltYmVyZ2VyLCBQYXVsaW5l|https://frl.publisso.de/adhoc/uri/VW50Y2gsIE1pY2hhZWw=|https://orcid.org/0000-0001-6099-7066|https://frl.publisso.de/adhoc/uri/S29sYmVyZywgSGFucy1DaHJpc3RpYW4=|https://frl.publisso.de/adhoc/uri/SGFydG1hbm4sIEFybmR0|https://frl.publisso.de/adhoc/uri/VGFyYW4sIEZsb3Jpbi1BbmRyZWk=|https://orcid.org/0000-0002-3467-4105|https://frl.publisso.de/adhoc/uri/V2FsbHdpZW5lciwgRGlldGhlbG0=|https://frl.publisso.de/adhoc/uri/QnJ1Y2tlciwgU2FyYSBZLg==|https://frl.publisso.de/adhoc/uri/U2NobmVld2Vpc3MsIEFuZHJlYXM=|https://frl.publisso.de/adhoc/uri/SMOkYmVybGUsIExvdGhhcg==|https://frl.publisso.de/adhoc/uri/Q291Y2gsIEZlcmd1cyBKLg==
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1000 Erstellt am 2025-07-05T08:23:29.434+0200
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