Molekulare Testungen zu therapeutischen Zwecken bei Brustkrebs – Hilfe für die klinische Praxis

Brustkrebs ist gekennzeichnet durch genetische Heterogenität, die durch erbliche und erworbene Faktoren geprägt ist. Molekulare Marker zu identifizieren, kann heutzutage individualisierte, zielgerichtete Therapien ermöglichen.
Trotz wachsenden Bewusstseins für die Bedeutung hierfür werden einfach verfügbare molekulargenetische Testungen oft nicht genutzt – somit bleibt ein relevanter Teil an Therapieoptionen für Patientinnen unzugänglich.

• Literatur

• 1 Berger MF, Mardis ER. The emerging clinical relevance of genomics in cancer medicine. Nat Rev Clin Oncol 2018; 15: 353-365
• 2 Sun L, Wu A, Bean GR. et al. Molecular Testing in Breast Cancer: Current Status and Future Directions. J Mol Diagn 2021; 23: 1422-1432
• 3 Tutt ANJ, Garber JE, Kaufman B. et al. Adjuvant Olaparib for Patients with BRCA1- or BRCA2-Mutated Breast Cancer. N Engl J Med 2021; 384: 2394-2405
• 4 Geyer jr. CE, Garber JE, Gelber RD. et al. Overall survival in the OlympiA phase III trial of adjuvant olaparib in patients with germline pathogenic variants in BRCA1/2 and high-risk, early breast cancer. Ann Oncol 2022; 33: 1250-1268
• 5 Robson ME, Tung N, Conte P. et al. OlympiAD final overall survival and tolerability results: Olaparib versus chemotherapy treatment of physician’s choice in patients with a germline BRCA mutation and HER2-negative metastatic breast cancer. Ann Oncol 2019; 30: 558-566
• 6 Robson ME, Im SA, Senkus E. et al. OlympiAD extended follow-up for overall survival and safety: Olaparib versus chemotherapy treatment of physician’s choice in patients with a germline BRCA mutation and HER2-negative metastatic breast cancer. Eur J Cancer 2023; 184: 39-47
• 7 Litton JK, Rugo HS, Ettl J. et al. Talazoparib in Patients with Advanced Breast Cancer and a Germline BRCA Mutation. N Engl J Med 2018; 379: 753-763
• 8 Bidard FC, Kaklamani VG, Neven P. et al. Elacestrant (oral selective estrogen receptor degrader) Versus Standard Endocrine Therapy for Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Results From the Randomized Phase III EMERALD Trial. J Clin Oncol 2022; 40: 3246-3256
• 9 Turner NC, Im SA, Saura C. et al. Inavolisib-Based Therapy in PIK3CA-Mutated Advanced Breast Cancer. N Engl J Med 2024; 391: 1584-1596
• 10 Turner NC, Oliveira M, Howell SJ. et al. Capivasertib in Hormone Receptor-Positive Advanced Breast Cancer. N Engl J Med 2023; 388: 2058-2070
• 11 Ahn HK, Kim JH, Koh SJ. et al. Prevalence of germline BRCA1/2 pathogenic variants in unselected Korean patients with HER2-negative metastatic breast cancer: a nationwide prospective study (KCSG BR19–10). Lancet Reg Health West Pac 2025; 60: 101622
• 12 Rhiem K, Zachariae S, Waha A. et al. Prevalence of Pathogenic Germline Variants in Women with Non-Familial Unilateral Triple-Negative Breast Cancer. Breast Care (Basel) 2023; 18: 106-112
• 13 Rhiem K, Bucker-Nott HJ, Hellmich M. et al. Benchmarking of a checklist for the identification of familial risk for breast and ovarian cancers in a prospective cohort. Breast J 2019; 25: 455-460
• 14 Engel C, Rhiem K, Hahnen E. et al. Prevalence of pathogenic BRCA1/2 germline mutations among 802 women with unilateral triple-negative breast cancer without family cancer history. BMC Cancer 2018; 18: 265
• 15 Anderson EJ, Mollon LE, Dean JL. et al. A Systematic Review of the Prevalence and Diagnostic Workup of PIK3CA Mutations in HR+/HER2− Metastatic Breast Cancer. Int J Breast Cancer 2020; 2020: 3759179
• 16 Armstrong N, Ryder S, Forbes C. et al. A systematic review of the international prevalence of BRCA mutation in breast cancer. Clin Epidemiol 2019; 11: 543-561
• 17 Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature 2012; 490: 61-70
• 18 Hu C, Polley EC, Yadav S. et al. The Contribution of Germline Predisposition Gene Mutations to Clinical Subtypes of Invasive Breast Cancer From a Clinical Genetic Testing Cohort. J Natl Cancer Inst 2020; 112: 1231-1241
• 19 Shimelis H, LaDuca H, Hu C. et al. Triple-Negative Breast Cancer Risk Genes Identified by Multigene Hereditary Cancer Panel Testing. J Natl Cancer Inst 2018; 110: 855-862
• 20 Shi Y, Jin J, Ji W. et al. Therapeutic landscape in mutational triple negative breast cancer. Mol Cancer 2018; 17: 99
• 21 Dent RA, Curigliano G, Hu X. et al. Exploratory biomarker analysis of trastuzumab deruxtecan (T-DXd) vs physician’s choice of chemotherapy (TPC) in HER2-low/ultralow, hormone receptor–positive (HR+) metastatic breast cancer (mBC) in DESTINY-Breast06 (DB-06). J Clin Oncol 2025; 43 (Suppl. 16) 1013-1013
• 22 Tung NM, Robson ME, Ventz S. et al. TBCRC 048: Phase II Study of Olaparib for Metastatic Breast Cancer and Mutations in Homologous Recombination-Related Genes. J Clin Oncol 2020; 38: 4274-4282
• 23 Jhaveri KL, Neven P, Casalnuovo ML. et al. Imlunestrant with or without Abemaciclib in Advanced Breast Cancer. N Engl J Med 2025; 392: 1189-1202
• 24 Jhaveri KL, Im SA, Saura C. et al. Overall Survival with Inavolisib in PIK3CA-Mutated Advanced Breast Cancer. N Engl J Med 2025; 393: 151-161
• 25 F. Hoffmann-La Roche Ltd.. European Commission approves Roche’s Itovebi for people with ER-positive, HER2-negative, advanced breast cancer with a PIK3CA mutation. Basel, Switzerland 2025 Zugriff am 28. Juli 2025 unter: https://www.roche.com/media/releases/med-cor-2025-07-23
• 26 Yadav S, Couch FJ, Hillman S. et al. Real-World Germline BRCA Testing, Poly(ADP-ribose) Polymerase Inhibitor Utilization, and Survival Outcomes in Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer. JCO Precis Oncol 2025; 9: e2400814
• 27 [Anonym]. Gendiagnostikgesetz vom 31. Juli 2009 (BGBl. I S. 2529, 3672), das zuletzt durch Artikel 15 Absatz 4 des Gesetzes vom 4. Mai 2021 (BGBl. I S. 882) geändert worden ist. Zugriff am 28. Juli 2025 unter: https://www.gesetze-im-internet.de/gendg/BJNR252900009.html
• 28 Hu C, Hart SN, Gnanaolivu R. et al. A Population-Based Study of Genes Previously Implicated in Breast Cancer. N Engl J Med 2021; 384: 440-451
• 29 Fasching PA, Yadav S, Hu C. 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; 39: 1619-1630
• 30 Hauke J, Horvath J, Gross E. et al. Gene panel testing of 5589 BRCA1/2-negative index patients with breast cancer in a routine diagnostic setting: results of the German Consortium for Hereditary Breast and Ovarian Cancer. Cancer Med 2018; 7: 1349-1358
• 31 Deutsche Krebsgesellschaft e. V.. Checkliste zur Erfassung der erblichen Belastung für Brust- oder Eierstockkrebs. Zugriff am 28. Juli 2025 unter: https://www.krebsgesellschaft.de/unsere-themen/zertifizierung/erhebungsboegen-und-dokumente?file=files/content/unsere-themen/zertifizierung/erhebungsboegen-und-dokumente/zentren-fuer-familiaeren-brust-und-eierstockkrebs/aktuell/checkliste_erbliche_belastung_brust_gyn-250219-1.xlsx
• 32 Deutsches Konsortium Familiärer Brust- und Eierstockkrebs. Curriculum Familiärer Brust- und Eierstockkrebs. Zugriff am 28. Juli 2025 unter: https://www.konsortium-familiaerer-brustkrebs.de/das-konsortium/curriculum-familiaerer-brust-und-eierstockkrebs/
• 33 Nagahashi M, Shimada Y, Ichikawa H. et al. Next generation sequencing-based gene panel tests for the management of solid tumors. Cancer Sci 2019; 110: 6-15
• 34 Popova L, Carabetta VJ. The use of next-generation sequencing in personalized medicine. ArXiv 2024;
• 35 Koboldt DC, Fulton RS, McLellan MD. et al. Comprehensive molecular portraits of human breast tumours. Nature 2012; 490: 61-70
• 36 Mosele MF, Westphalen CB, Stenzinger A. et al. Recommendations for the use of next-generation sequencing (NGS) for patients with advanced cancer in 2024: a report from the ESMO Precision Medicine Working Group. Ann Oncol 2024; 35: 588-606
• 37 Turner NC, Mayer EL, Park YH. et al. Camizestrant + CDK4/6 inhibitor (CDK4/6i) for the treatment of emergent ESR1 mutations during first-line (1L) endocrine-based therapy (ET) and ahead of disease progression in patients (pts) with HR+/HER2– advanced breast cancer (ABC): Phase 3, double-blind ctDNA-guided SERENA-6 trial. J Clin Oncol 2025; 43 (Suppl. 17) LBA4-LBA4
• 38 KBV. Praxisinfo: Humangenetik nach EBM. 2016
• 39 (KBV) KB. Praxisinformation: Genehmigungspflicht Humangenetik – EBM-Update (Teil A & B). 2021
• 40 (KBV) KB. Genetische Untersuchungen in der vertragsärztlichen Versorgung – Hinweise für veranlassende Ärztinnen und Ärzte. 2024 Zugriff am 28. Juli 2025 unter: https://www.kbv.de/documents/infothek/publikationen/praxisinfo/praxisinfospezial-genetik.pdf