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Erschienen in:

28.08.2023 | Pathologie

Personalisierte Medizin – von der Translation zur Klinik

verfasst von: Prof. Dr. Marcus Schmidt, Prof. Dr. Carsten Denkert, Prof. Dr. Kerstin Rhiem, Prof. Dr. Thomas Decker, Prof. Dr. Sibylle Loibl

Erschienen in: Wiener klinisches Magazin | Ausgabe 4/2023

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Zusammenfassung

Hintergrund

Mutationsanalysen spielen eine zunehmende Rolle bei der Therapie des fortgeschrittenen Mammakarzinoms.

Ziel der Arbeit

Darstellung der Evidenz für eine personalisierte Therapie beim Mammakarzinom.

Material und Methode

Die vorliegende Evidenz und standardisierte Einteilungen zur Therapierelevanz werden erläutert.

Ergebnisse

Die Therapierelevanz genomischer Alterationen wird von Fachgesellschaften wie der European Society for Medical Oncology (ESMO), der American Society for Medical Oncology (ASCO) und der Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) beurteilt. Metastasierte Mammakarzinompatientinnen, die mittels zielgerichteten Therapien der ESMO Scale of Clinical Actionability for molecular Targets (ESCAT) Stufe I und II behandelt worden waren, haben ein signifikant verbessertes progressionsfreies Überleben.

Schlussfolgerung

Evidenzbasierte personalisierte Medizin kann die Therapie des fortgeschrittenen Mammakarzinoms verbessern.

Vorheriger Artikel Klinisch relevante molekularpathologische Diagnostik beim Mammakarzinom

Wahida A, Buschhorn L, Fröhling S, Jost PJ, Schneeweiss A, Lichter P, Kurzrock R (2023) The coming decade in precision oncology: six riddles. Nat Rev Cancer 23(1):43–54. https://doi.org/10.1038/s41568-022-00529-3CrossRefPubMed

Mateo J, Chakravarty D, Dienstmann R, Jezdic S, Gonzalez-Perez A, Lopez-Bigas N, Ng CKY, Bedard PL, Tortora G, Douillard J‑Y, van Allen EM, Schultz N, Swanton C, André F, Pusztai L (2018) A framework to rank genomic alterations as targets for cancer precision medicine: the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT). Ann Oncol 29(9):1895–1902. https://doi.org/10.1093/annonc/mdy263CrossRefPubMedPubMedCentral

Litton JK, Rugo HS, Ettl J, Hurvitz SA, Goncalves A, Lee K‑H, Fehrenbacher L, Yerushalmi R, Mina LA, Martin M, Roche H, Im Y‑H, Quek RGW, Markova D, Tudor IC, Hannah AL, Eiermann W, Blum JL (2018) Talazoparib in patients with advanced breast cancer and a germline BRCA mutation. N Engl J Med. https://doi.org/10.1056/NEJMoa1802905CrossRefPubMed

Robson M, Im S‑A, Senkus E, Xu B, Domchek SM, Masuda N, Delaloge S, Li W, Tung N, Armstrong A, Wu W, Goessl C, Runswick S, Conte P (2017) Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med 377(6):523–533. https://doi.org/10.1056/NEJMoa1706450CrossRefPubMed

Robson ME, Tung N, Conte P, Im S‑A, Senkus E, Xu B, Masuda N, Delaloge S, Li W, Armstrong A, Wu W, Goessl C, Runswick S, Domchek SM (2019) 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 30(4):558–566. https://doi.org/10.1093/annonc/mdz012CrossRefPubMedPubMedCentral

Tung NM, Robson ME, Ventz S, Santa-Maria CA, Nanda R, Marcom PK, Shah PD, Ballinger TJ, Yang ES, Vinayak S, Melisko M, Brufsky A, DeMeo M, Jenkins C, Domchek S, D’Andrea A, Lin NU, Hughes ME, Carey LA, Wagle N, Wulf GM, Krop IE, Wolff AC, Winer EP, Garber JE (2020) TBCRC 048: phase II study of olaparib for metastatic breast cancer and mutations in homologous recombination-related genes. J Clin Oncol 38(36):4274–4282. https://doi.org/10.1200/JCO.20.02151CrossRefPubMed

Araya CL, Cenik C, Reuter JA, Kiss G, Pande VS, Snyder MP, Greenleaf WJ (2016) Identification of significantly mutated regions across cancer types highlights a rich landscape of functional molecular alterations. Nat Genet 48(2):117–125. https://doi.org/10.1038/ng.3471CrossRefPubMed

Lawrence MS, Stojanov P, Polak P et al (2013) Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature 499(7457):214–218. https://doi.org/10.1038/nature12213CrossRefPubMedPubMedCentral

Lawrence MS, Stojanov P, Mermel CH, Robinson JT, Garraway LA, Golub TR, Meyerson M, Gabriel SB, Lander ES, Getz G (2014) Discovery and saturation analysis of cancer genes across 21 tumour types. Nature 505(7484):495–501. https://doi.org/10.1038/nature12912CrossRefPubMedPubMedCentral

10.

Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA, Kinzler KW (2013) Cancer genome landscapes. Science 339(6127):1546–1558. https://doi.org/10.1126/science.1235122CrossRefPubMedPubMedCentral

11.

André F, Ciruelos E, Rubovszky G, Campone M, Loibl S, Rugo HS, Iwata H, Conte P, Mayer IA, Kaufman B, Yamashita T, Lu Y‑S, Inoue K, Takahashi M, Pápai Z, Longin A‑S, Mills D, Wilke C, Hirawat S, Juric D (2019) Alpelisib for PIK3CA-mutated, hormone receptor-positive advanced breast cancer. N Engl J Med 380(20):1929–1940. https://doi.org/10.1056/NEJMoa1813904CrossRefPubMed

12.

Howell SJ, Casbard A, Carucci M, Ingarfield K, Butler R, Morgan S, Meissner M, Bale C, Bezecny P, Moon S, Twelves C, Venkitaraman R, Waters S, de Bruin EC, Schiavon G, Foxley A, Jones RH (2022) Fulvestrant plus capivasertib versus placebo after relapse or progression on an aromatase inhibitor in metastatic, oestrogen receptor-positive, HER2-negative breast cancer (FAKTION): overall survival, updated progression-free survival, and expanded biomarker analysis from a randomised, phase 2 trial. Lancet Oncol 23(7):851–864. https://doi.org/10.1016/S1470-2045(22)00284-4CrossRefPubMedPubMedCentral

13.

Schmid P, Abraham J, Chan S, Wheatley D, Brunt AM, Nemsadze G, Baird RD, Park YH, Hall PS, Perren T, Stein RC, Mangel L, Ferrero J‑M, Phillips M, Conibear J, Cortes J, Foxley A, de Bruin EC, McEwen R, Stetson D, Dougherty B, Sarker S‑J, Prendergast A, McLaughlin-Callan M, Burgess M, Lawrence C, Cartwright H, Mousa K, Turner NC (2020) Capivasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer: the PAKT trial. J Clin Oncol 38(5):423–433. https://doi.org/10.1200/JCO.19.00368CrossRefPubMed

14.

Fribbens C, O’Leary B, Kilburn L, Hrebien S, Garcia-Murillas I, Beaney M, Cristofanilli M, Andre F, Loi S, Loibl S, Jiang J, Bartlett CH, Koehler M, Dowsett M, Bliss JM, Johnston SRD, Turner NC (2016) Plasma ESR1 mutations and the treatment of estrogen receptor-positive advanced breast cancer. J Clin Oncol 34(25):2961–2968. https://doi.org/10.1200/JCO.2016.67.3061CrossRefPubMed

15.

Turner NC, Swift C, Kilburn L, Fribbens C, Beaney M, Garcia-Murillas I, Budzar AU, Robertson JFR, Gradishar W, Piccart M, Schiavon G, Bliss JM, Dowsett M, Johnston SRD, Chia SK (2020) ESR1 mutations and overall survival on fulvestrant versus exemestane in advanced hormone receptor-positive breast cancer: a combined analysis of the phase III soFEA and EFECT trials. Clin Cancer Res 26(19):5172–5177. https://doi.org/10.1158/1078-0432.CCR-20-0224CrossRefPubMed

16.

Bidard F‑C, Hardy-Bessard A‑C, Dalenc F et al (2022) Switch to fulvestrant and palbociclib versus no switch in advanced breast cancer with rising ESR1 mutation during aromatase inhibitor and palbociclib therapy (PADA-1): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol 23(11):1367–1377. https://doi.org/10.1016/S1470-2045(22)00555-1CrossRefPubMed

17.

Bidard F‑C, Kaklamani VG, Neven P, Streich G, Montero AJ, Forget F, Mouret-Reynier M‑A, Sohn JH, Taylor D, Harnden KK, Khong H, Kocsis J, Dalenc F, Dillon PM, Babu S, Waters S, Deleu I, García Sáenz JA, Bria E, Cazzaniga M, Lu J, Aftimos P, Cortés J, Liu S, Tonini G, Laurent D, Habboubi N, Conlan MG, Bardia A (2022) 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 40(28):3246–3256. https://doi.org/10.1200/JCO.22.00338CrossRefPubMedPubMedCentral

18.

Ma CX, Bose R, Gao F, Freedman RA, Telli ML, Kimmick G, Winer E, Naughton M, Goetz MP, Russell C, Tripathy D, Cobleigh M, Forero A, Pluard TJ, Anders C, Niravath PA, Thomas S, Anderson J, Bumb C, Banks KC, Lanman RB, Bryce R, Lalani AS, Pfeifer J, Hayes DF, Pegram M, Blackwell K, Bedard PL, Al-Kateb H, Ellis MJ (2017) Neratinib efficacy and circulating tumor DNA detection of HER2 mutations in HER2 nonamplified metastatic breast cancer. Clin Cancer Res 23(19):5687–5695. https://doi.org/10.1158/1078-0432.CCR-17-0900CrossRefPubMedPubMedCentral

19.

Nayar U, Cohen O, Kapstad C, Cuoco MS, Waks AG, Wander SA, Painter C, Freeman S, Persky NS, Marini L, Helvie K, Oliver N, Rozenblatt-Rosen O, Ma CX, Regev A, Winer EP, Lin NU, Wagle N (2019) Acquired HER2 mutations in ER+ metastatic breast cancer confer resistance to estrogen receptor-directed therapies. Nat Genet 51(2):207–216. https://doi.org/10.1038/s41588-018-0287-5CrossRefPubMed

20.

Remoué A, Conan-Charlet V, Bourhis A, Le Flahec G, Lambros L, Marcorelles P, Uguen A (2019) Non-secretory breast carcinomas lack NTRK rearrangements and TRK protein expression. Pathol Int 69(2):94–96. https://doi.org/10.1111/pin.12766CrossRefPubMed

21.

Dudley JC, Lin M‑T, Le DT, Eshleman JR (2016) Microsatellite instability as a biomarker for PD‑1 blockade. Clin Cancer Res 22(4):813–820. https://doi.org/10.1158/1078-0432.CCR-15-1678CrossRefPubMed

22.

Shao C, Li G, Huang L, Pruitt S, Castellanos E, Frampton G, Carson KR, Snow T, Singal G, Fabrizio D, Alexander BM, Jin F, Zhou W (2020) Prevalence of high tumor mutational burden and association with survival in patients with less common solid tumors. JAMA Netw Open 3(10):e2025109. https://doi.org/10.1001/jamanetworkopen.2020.25109CrossRefPubMedPubMedCentral

23.

Chakravarty D, Johnson A, Sklar J, Lindeman NI, Moore K, Ganesan S, Lovly CM, Perlmutter J, Gray SW, Hwang J, Lieu C, André F, Azad N, Borad M, Tafe L, Messersmith H, Robson M, Meric-Bernstam F (2022) Somatic genomic testing in patients with metastatic or advanced cancer: ASCO provisional clinical opinion. J Clin Oncol 40(11):1231–1258. https://doi.org/10.1200/JCO.21.02767CrossRefPubMed

24.

Condorelli R, Mosele F, Verret B, Bachelot T, Bedard PL, Cortes J, Hyman DM, Juric D, Krop I, Bieche I, Saura C, Sotiriou C, Cardoso F, Loibl S, Andre F, Turner NC (2019) Genomic alterations in breast cancer: level of evidence for actionability according to ESMO Scale for Clinical Actionability of molecular Targets (ESCAT). Ann Oncol 30(3):365–373. https://doi.org/10.1093/annonc/mdz036CrossRefPubMed

25.

Mosele F, Remon J, Mateo J, Westphalen CB, Barlesi F, Lolkema MP, Normanno N, Scarpa A, Robson M, Meric-Bernstam F, Wagle N, Stenzinger A, Bonastre J, Bayle A, Michiels S, Bièche I, Rouleau E, Jezdic S, Douillard J‑Y, Reis-Filho JS, Dienstmann R, André F (2020) Recommendations for the use of next-generation sequencing (NGS) for patients with metastatic cancers: a report from the ESMO Precision Medicine Working Group. Ann Oncol 31(11):1491–1505. https://doi.org/10.1016/j.annonc.2020.07.014CrossRefPubMed

26.

Henry NL, Somerfield MR, Dayao Z, Elias A, Kalinsky K, McShane LM, Moy B, Park BH, Shanahan KM, Sharma P, Shatsky R, Stringer-Reasor E, Telli M, Turner NC, DeMichele A (2022) Biomarkers for systemic therapy in metastatic breast cancer: ASCO guideline update. J Clin Oncol 40(27):3205–3221. https://doi.org/10.1200/JCO.22.01063CrossRefPubMed

27.

Ditsch N, Wöcke A, Untch M et al (2022) AGO recommendations for the diagnosis and treatment of patients with early breast cancer: update 2022. Breast Care 17(4):403–420. https://doi.org/10.1159/000524879CrossRefPubMedPubMedCentral

28.

Thill M, Lüftner D, Kolberg-Liedtke C et al (2022) AGO recommendations for the diagnosis and treatment of patients with locally advanced and metastatic breast cancer: update 2022. Breast Care 17(4):421–429. https://doi.org/10.1159/000524789CrossRefPubMedPubMedCentral

29.

Andre F, Filleron T, Kamal M et al (2022) Genomics to select treatment for patients with metastatic breast cancer. Nature 610(7931):343–348. https://doi.org/10.1038/s41586-022-05068-3CrossRefPubMed

30.

Pixberg C, Zapatka M, Hlevnjak M et al (2022) COGNITION: a prospective precision oncology trial for patients with early breast cancer at high risk following neoadjuvant chemotherapy. ESMO Open 7(6):100637. https://doi.org/10.1016/j.esmoop.2022.100637CrossRefPubMedPubMedCentral

Titel: Personalisierte Medizin – von der Translation zur Klinik
verfasst von: Prof. Dr. Marcus Schmidt
Prof. Dr. Carsten Denkert
Prof. Dr. Kerstin Rhiem
Prof. Dr. Thomas Decker
Prof. Dr. Sibylle Loibl
Publikationsdatum: 28.08.2023
Verlag: Springer Vienna
Erschienen in: Wiener klinisches Magazin / Ausgabe 4/2023
Print ISSN: 1869-1757
Elektronische ISSN: 1613-7817
DOI: https://doi.org/10.1007/s00740-023-00502-2

Springer Medizin Österreich

Zusammenfassung

Hintergrund

Ziel der Arbeit

Material und Methode

Ergebnisse

Schlussfolgerung

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