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Erschienen in: Die Gynäkologie 3/2021

24.02.2021 | Mammakarzinom | Leitthema

NGS zur Selektion innovativer Therapien – Was bringt das?

verfasst von: Carla E. Schulmeyer, Simon Bader, Hanna Hübner, Matthias Rübner, Prof. Dr. Peter A. Fasching

Erschienen in: Die Gynäkologie | Ausgabe 3/2021

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Zusammenfassung

Next Generation Sequencing (NGS) beschreibt eine Technologie zur Sequenzierung des gesamten Genoms, Exoms und Transkriptoms und hat die genomische Forschung revolutioniert. Im Vergleich zur Sanger-Sequenzierung kann nun ein komplettes menschliches Genom binnen eines Tages sequenziert werden. Die Ergebnisse können mit menschlichen Referenzgenomen abgeglichen werden. Durch Fragmentation der DNA, Adaption mittels Adapter an die Bruchstücke und Amplifikation der Fragmente erfolgt eine bioinformatische Analyse, die in Form eines DNA-Chips gespeichert und sequenziert wird. NGS findet viele Anwendungsbereiche, vor allem in der genetischen, mikrobiologischen und onkologischen Forschung, und hat sich bisher noch nicht flächendeckend im klinischen Alltag etabliert. In der Gynäkologie wird NGS insbesondere in der nichtinvasiven Pränataldiagnostik (NIPT), in der Reproduktionsmedizin und in der Onkologie eingesetzt.
Literatur
1.
Zurück zum Zitat Watson JD, Crick FHC (1953) Molecular structure of nucleic acids: a structure for deoxyribose nucleic acid. Nature 171(4356):737–738PubMed Watson JD, Crick FHC (1953) Molecular structure of nucleic acids: a structure for deoxyribose nucleic acid. Nature 171(4356):737–738PubMed
2.
Zurück zum Zitat Hall JM et al (1990) Linkage of early-onset familial breast cancer to chromosome 17q21. Science 250(4988):1684–1689PubMed Hall JM et al (1990) Linkage of early-onset familial breast cancer to chromosome 17q21. Science 250(4988):1684–1689PubMed
3.
Zurück zum Zitat McPherson JD et al (2001) A physical map of the human genome. Nature 409(6822):934–941PubMed McPherson JD et al (2001) A physical map of the human genome. Nature 409(6822):934–941PubMed
4.
Zurück zum Zitat Venter JC et al (2001) The sequence of the human genome. Science 291(5507):1304–1351PubMed Venter JC et al (2001) The sequence of the human genome. Science 291(5507):1304–1351PubMed
5.
Zurück zum Zitat Hartkopf AD et al (2019) Update breast cancer 2019 part 1 - implementation of study results of novel study designs in clinical practice in patients with early breast cancer. Geburtshilfe Frauenheilkd 79(3):256–267PubMedPubMedCentral Hartkopf AD et al (2019) Update breast cancer 2019 part 1 - implementation of study results of novel study designs in clinical practice in patients with early breast cancer. Geburtshilfe Frauenheilkd 79(3):256–267PubMedPubMedCentral
6.
Zurück zum Zitat Janni W et al (2019) Update breast cancer 2019 part 2 - implementation of novel diagnostics and therapeutics in advanced breast cancer patients in clinical practice. Geburtshilfe Frauenheilkd 79(3):268–280PubMedPubMedCentral Janni W et al (2019) Update breast cancer 2019 part 2 - implementation of novel diagnostics and therapeutics in advanced breast cancer patients in clinical practice. Geburtshilfe Frauenheilkd 79(3):268–280PubMedPubMedCentral
7.
Zurück zum Zitat Kolberg HC et al (2019) Update breast cancer 2019 part 3 - current developments in early breast cancer: review and critical assessment by an international expert panel. Geburtshilfe Frauenheilkd 79(5):470–482PubMedPubMedCentral Kolberg HC et al (2019) Update breast cancer 2019 part 3 - current developments in early breast cancer: review and critical assessment by an international expert panel. Geburtshilfe Frauenheilkd 79(5):470–482PubMedPubMedCentral
8.
Zurück zum Zitat Schutz F et al (2019) Update breast cancer 2019 part 4 - diagnostic and therapeutic challenges of new, personalised therapies for patients with early breast cancer. Geburtshilfe Frauenheilkd 79(10):1079–1089PubMedPubMedCentral Schutz F et al (2019) Update breast cancer 2019 part 4 - diagnostic and therapeutic challenges of new, personalised therapies for patients with early breast cancer. Geburtshilfe Frauenheilkd 79(10):1079–1089PubMedPubMedCentral
9.
Zurück zum Zitat Welslau M et al (2019) Update breast cancer 2019 part 5 - diagnostic and therapeutic challenges of new, personalised therapies in patients with advanced breast cancer. Geburtshilfe Frauenheilkd 79(10):1090–1099PubMedPubMedCentral Welslau M et al (2019) Update breast cancer 2019 part 5 - diagnostic and therapeutic challenges of new, personalised therapies in patients with advanced breast cancer. Geburtshilfe Frauenheilkd 79(10):1090–1099PubMedPubMedCentral
10.
Zurück zum Zitat Luftner D et al (2020) Update breast cancer 2020 part 2 - advanced breast cancer: new treatments and implementation of therapies with companion diagnostics. Geburtshilfe Frauenheilkd 80(4):391–398PubMedPubMedCentral Luftner D et al (2020) Update breast cancer 2020 part 2 - advanced breast cancer: new treatments and implementation of therapies with companion diagnostics. Geburtshilfe Frauenheilkd 80(4):391–398PubMedPubMedCentral
11.
Zurück zum Zitat Schneeweiss A et al (2020) Update breast cancer 2020 part 1 - early breast cancer: consolidation of knowledge about known therapies. Geburtshilfe Frauenheilkd 80(3):277–287PubMedPubMedCentral Schneeweiss A et al (2020) Update breast cancer 2020 part 1 - early breast cancer: consolidation of knowledge about known therapies. Geburtshilfe Frauenheilkd 80(3):277–287PubMedPubMedCentral
12.
Zurück zum Zitat Tutt ANJ et al (2015) OlympiA: A randomized phase III trial of olaparib as adjuvant therapy in patients with high-risk HER2-negative breast cancer (BC) and a germline BRCA1/2 mutation (gBRCAm). J Clin Oncol 33(15_suppl):TPS1109–TPS1109 Tutt ANJ et al (2015) OlympiA: A randomized phase III trial of olaparib as adjuvant therapy in patients with high-risk HER2-negative breast cancer (BC) and a germline BRCA1/2 mutation (gBRCAm). J Clin Oncol 33(15_suppl):TPS1109–TPS1109
13.
Zurück zum Zitat André F et al (2019) Alpelisib for PIK3CA-mutated, hormone receptor–positive advanced breast cancer. N Engl J Med 380(20):1929–1940PubMed André F et al (2019) Alpelisib for PIK3CA-mutated, hormone receptor–positive advanced breast cancer. N Engl J Med 380(20):1929–1940PubMed
14.
Zurück zum Zitat André T et al (2020) Pembrolizumab in microsatellite-instability–high advanced colorectal cancer. N Engl J Med 383(23):2207–2218PubMed André T et al (2020) Pembrolizumab in microsatellite-instability–high advanced colorectal cancer. N Engl J Med 383(23):2207–2218PubMed
15.
Zurück zum Zitat Drilon A et al (2018) Efficacy of larotrectinib in TRK fusion-positive cancers in adults and children. N Engl J Med 378(8):731–739PubMedPubMedCentral Drilon A et al (2018) Efficacy of larotrectinib in TRK fusion-positive cancers in adults and children. N Engl J Med 378(8):731–739PubMedPubMedCentral
16.
Zurück zum Zitat Margulies M et al (2005) Genome sequencing in microfabricated high-density picolitre reactors. Nature 437(7057):376–380PubMedPubMedCentral Margulies M et al (2005) Genome sequencing in microfabricated high-density picolitre reactors. Nature 437(7057):376–380PubMedPubMedCentral
17.
Zurück zum Zitat Sanger F, Coulson AR (1975) A rapid method for determining sequences in DNA by primed synthesis with DNA polymerase. J Mol Biol 94(3):441–448PubMed Sanger F, Coulson AR (1975) A rapid method for determining sequences in DNA by primed synthesis with DNA polymerase. J Mol Biol 94(3):441–448PubMed
18.
19.
Zurück zum Zitat Xiao T, Zhou W (2020) The third generation sequencing: the advanced approach to genetic diseases. Transl Pediatr 9(2):163–173PubMedPubMedCentral Xiao T, Zhou W (2020) The third generation sequencing: the advanced approach to genetic diseases. Transl Pediatr 9(2):163–173PubMedPubMedCentral
21.
Zurück zum Zitat Schwarze K et al (2018) Are whole-exome and whole-genome sequencing approaches cost-effective? A systematic review of the literature. Genet Med 20(10):1122–1130PubMed Schwarze K et al (2018) Are whole-exome and whole-genome sequencing approaches cost-effective? A systematic review of the literature. Genet Med 20(10):1122–1130PubMed
22.
Zurück zum Zitat Timms KM et al (2014) Association of BRCA1/2 defects with genomic scores predictive of DNA damage repair deficiency among breast cancer subtypes. Breast Cancer Res 16(6):475PubMedPubMedCentral Timms KM et al (2014) Association of BRCA1/2 defects with genomic scores predictive of DNA damage repair deficiency among breast cancer subtypes. Breast Cancer Res 16(6):475PubMedPubMedCentral
23.
Zurück zum Zitat Perou CM et al (2000) Molecular portraits of human breast tumours. Nature 406(6797):747–752PubMed Perou CM et al (2000) Molecular portraits of human breast tumours. Nature 406(6797):747–752PubMed
24.
Zurück zum Zitat Antoniou AC et al (2010) A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population. Nat Genet 42(10):885–892PubMedPubMedCentral Antoniou AC et al (2010) A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population. Nat Genet 42(10):885–892PubMedPubMedCentral
25.
Zurück zum Zitat Bojesen SE et al (2013) Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer. Nat Genet 45(4):371–384, 384e1‑2PubMedPubMedCentral Bojesen SE et al (2013) Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer. Nat Genet 45(4):371–384, 384e1‑2PubMedPubMedCentral
27.
Zurück zum Zitat Couch FJ et al (2016) Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer. Nat Commun 7:11375PubMedPubMedCentral Couch FJ et al (2016) Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer. Nat Commun 7:11375PubMedPubMedCentral
28.
Zurück zum Zitat Day FR et al (2015) Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair. Nat Genet 47(11):1294–1303PubMedPubMedCentral Day FR et al (2015) Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair. Nat Genet 47(11):1294–1303PubMedPubMedCentral
29.
Zurück zum Zitat Dunning AM et al (2016) Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170. Nat Genet 48(4):374–386PubMedPubMedCentral Dunning AM et al (2016) Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170. Nat Genet 48(4):374–386PubMedPubMedCentral
30.
Zurück zum Zitat Escala-Garcia M et al (2020) A network analysis to identify mediators of germline-driven differences in breast cancer prognosis. Nat Commun 11(1):312PubMedPubMedCentral Escala-Garcia M et al (2020) A network analysis to identify mediators of germline-driven differences in breast cancer prognosis. Nat Commun 11(1):312PubMedPubMedCentral
32.
Zurück zum Zitat Ferreira MA et al (2019) Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer. Nat Commun 10(1):1741–1741PubMedPubMedCentral Ferreira MA et al (2019) Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer. Nat Commun 10(1):1741–1741PubMedPubMedCentral
33.
Zurück zum Zitat Garcia-Closas M et al (2013) Genome-wide association studies identify four ER negative-specific breast cancer risk loci. Nat Genet 45(4):392–398, 398e1‑2PubMedPubMedCentral Garcia-Closas M et al (2013) Genome-wide association studies identify four ER negative-specific breast cancer risk loci. Nat Genet 45(4):392–398, 398e1‑2PubMedPubMedCentral
34.
Zurück zum Zitat Ghoussaini M et al (2018) Publisher Correction: Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation. Nat Commun 9:16193PubMedPubMedCentral Ghoussaini M et al (2018) Publisher Correction: Evidence that breast cancer risk at the 2q35 locus is mediated through IGFBP5 regulation. Nat Commun 9:16193PubMedPubMedCentral
35.
Zurück zum Zitat Ghoussaini M et al (2012) Genome-wide association analysis identifies three new breast cancer susceptibility loci. Nat Genet 44(3):312–318PubMedPubMedCentral Ghoussaini M et al (2012) Genome-wide association analysis identifies three new breast cancer susceptibility loci. Nat Genet 44(3):312–318PubMedPubMedCentral
36.
Zurück zum Zitat Haiman CA et al (2011) A common variant at the TERT-CLPTM1L locus is associated with estrogen receptor-negative breast cancer. Nat Genet 43(12):1210–1214PubMedPubMedCentral Haiman CA et al (2011) A common variant at the TERT-CLPTM1L locus is associated with estrogen receptor-negative breast cancer. Nat Genet 43(12):1210–1214PubMedPubMedCentral
37.
Zurück zum Zitat Lawrenson K et al (2016) Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus. Nat Commun 7:12675PubMedPubMedCentral Lawrenson K et al (2016) Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus. Nat Commun 7:12675PubMedPubMedCentral
38.
Zurück zum Zitat Lindstrom S et al (2015) Corrigendum: genome-wide association study identifies multiple loci associated with both mammographic density and breast cancer risk. Nat Commun 6:8358PubMed Lindstrom S et al (2015) Corrigendum: genome-wide association study identifies multiple loci associated with both mammographic density and breast cancer risk. Nat Commun 6:8358PubMed
39.
Zurück zum Zitat Michailidou K et al (2013) Large-scale genotyping identifies 41 new loci associated with breast cancer risk. Nat Genet 45(4):353–361, 361e1‑2PubMedPubMedCentral Michailidou K et al (2013) Large-scale genotyping identifies 41 new loci associated with breast cancer risk. Nat Genet 45(4):353–361, 361e1‑2PubMedPubMedCentral
40.
Zurück zum Zitat Michailidou K et al (2017) Association analysis identifies 65 new breast cancer risk loci. Nature 551(7678):92–94PubMedPubMedCentral Michailidou K et al (2017) Association analysis identifies 65 new breast cancer risk loci. Nature 551(7678):92–94PubMedPubMedCentral
41.
Zurück zum Zitat Milne RL et al (2017) Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer. Nat Genet 49(12):1767–1778PubMedPubMedCentral Milne RL et al (2017) Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer. Nat Genet 49(12):1767–1778PubMedPubMedCentral
42.
Zurück zum Zitat Schmidt MK et al (2016) Age- and tumor subtype-specific breast cancer risk estimates for CHEK2*1100delC carriers. J Clin Oncol 34(23):2750–2760PubMedPubMedCentral Schmidt MK et al (2016) Age- and tumor subtype-specific breast cancer risk estimates for CHEK2*1100delC carriers. J Clin Oncol 34(23):2750–2760PubMedPubMedCentral
43.
Zurück zum Zitat Weischer M et al (2012) CHEK2*1100delC heterozygosity in women with breast cancer associated with early death, breast cancer-specific death, and increased risk of a second breast cancer. J Clin Oncol 30(35):4308–4316PubMedPubMedCentral Weischer M et al (2012) CHEK2*1100delC heterozygosity in women with breast cancer associated with early death, breast cancer-specific death, and increased risk of a second breast cancer. J Clin Oncol 30(35):4308–4316PubMedPubMedCentral
44.
Zurück zum Zitat Wu L et al (2018) A transcriptome-wide association study of 229,000 women identifies new candidate susceptibility genes for breast cancer. Nat Genet Wu L et al (2018) A transcriptome-wide association study of 229,000 women identifies new candidate susceptibility genes for breast cancer. Nat Genet
45.
Zurück zum Zitat Zhang H et al (2020) Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses. Nat Genet 52(6):572–581PubMedPubMedCentral Zhang H et al (2020) Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses. Nat Genet 52(6):572–581PubMedPubMedCentral
46.
Zurück zum Zitat Glubb DM et al (2021) Cross-cancer genome-wide association study of endometrial cancer and epithelial ovarian cancer identifies genetic risk regions associated with risk of both cancers. Cancer Epidemiol Biomarkers Prev 30(1):217–228PubMed Glubb DM et al (2021) Cross-cancer genome-wide association study of endometrial cancer and epithelial ovarian cancer identifies genetic risk regions associated with risk of both cancers. Cancer Epidemiol Biomarkers Prev 30(1):217–228PubMed
47.
Zurück zum Zitat Talhouk A et al (2020) Development and validation of the gene expression predictor of high-grade serous ovarian carcinoma molecular subTYPE (PrOTYPE). Clin Cancer Res 26(20):5411–5423PubMedPubMedCentral Talhouk A et al (2020) Development and validation of the gene expression predictor of high-grade serous ovarian carcinoma molecular subTYPE (PrOTYPE). Clin Cancer Res 26(20):5411–5423PubMedPubMedCentral
48.
Zurück zum Zitat Millstein J et al (2020) Prognostic gene expression signature for high-grade serous ovarian cancer. Ann Oncol 31(9):1240–1250PubMed Millstein J et al (2020) Prognostic gene expression signature for high-grade serous ovarian cancer. Ann Oncol 31(9):1240–1250PubMed
49.
Zurück zum Zitat Yang Y et al (2019) Genetic data from nearly 63,000 women of European descent predicts DNA methylation biomarkers and epithelial ovarian cancer risk. Cancer Res 79(3):505–517PubMed Yang Y et al (2019) Genetic data from nearly 63,000 women of European descent predicts DNA methylation biomarkers and epithelial ovarian cancer risk. Cancer Res 79(3):505–517PubMed
50.
Zurück zum Zitat Jiang X et al (2019) Publisher correction: shared heritability and functional enrichment across six solid cancers. Nat Commun 10(1):4386PubMedPubMedCentral Jiang X et al (2019) Publisher correction: shared heritability and functional enrichment across six solid cancers. Nat Commun 10(1):4386PubMedPubMedCentral
51.
Zurück zum Zitat Jiang X et al (2019) Shared heritability and functional enrichment across six solid cancers. Nat Commun 10(1):431PubMedPubMedCentral Jiang X et al (2019) Shared heritability and functional enrichment across six solid cancers. Nat Commun 10(1):431PubMedPubMedCentral
52.
Zurück zum Zitat Wunderle M et al (2018) Risk, prediction and prevention of hereditary breast cancer - large-scale genomic studies in times of big and smart data. Geburtshilfe Frauenheilkd 78(5):481–492PubMedPubMedCentral Wunderle M et al (2018) Risk, prediction and prevention of hereditary breast cancer - large-scale genomic studies in times of big and smart data. Geburtshilfe Frauenheilkd 78(5):481–492PubMedPubMedCentral
53.
Zurück zum Zitat Paik S et al (2004) A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med 351(27):2817–2826PubMed Paik S et al (2004) A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med 351(27):2817–2826PubMed
54.
Zurück zum Zitat Kronenwett R et al (2012) Decentral gene expression analysis: analytical validation of the Endopredict genomic multianalyte breast cancer prognosis test. BMC Cancer 12:456PubMedPubMedCentral Kronenwett R et al (2012) Decentral gene expression analysis: analytical validation of the Endopredict genomic multianalyte breast cancer prognosis test. BMC Cancer 12:456PubMedPubMedCentral
55.
Zurück zum Zitat Buyse M et al (2006) Validation and clinical utility of a 70-gene prognostic signature for women with node-negative breast cancer. J Natl Cancer Inst 98(17):1183–1192PubMed Buyse M et al (2006) Validation and clinical utility of a 70-gene prognostic signature for women with node-negative breast cancer. J Natl Cancer Inst 98(17):1183–1192PubMed
56.
Zurück zum Zitat Pu M et al (2020) Research-based PAM50 signature and long-term breast cancer survival. Breast Cancer Res Treat 179(1):197–206PubMed Pu M et al (2020) Research-based PAM50 signature and long-term breast cancer survival. Breast Cancer Res Treat 179(1):197–206PubMed
57.
Zurück zum Zitat Okkenhaug K, Vanhaesebroeck B (2001) New responsibilities for the PI3K regulatory subunit p85 alpha. Sci STKE 2001(65):pe1PubMed Okkenhaug K, Vanhaesebroeck B (2001) New responsibilities for the PI3K regulatory subunit p85 alpha. Sci STKE 2001(65):pe1PubMed
58.
Zurück zum Zitat Janku F (2017) Phosphoinositide 3‑kinase (PI3K) pathway inhibitors in solid tumors: from laboratory to patients. Cancer Treat Rev 59:93–101PubMed Janku F (2017) Phosphoinositide 3‑kinase (PI3K) pathway inhibitors in solid tumors: from laboratory to patients. Cancer Treat Rev 59:93–101PubMed
59.
Zurück zum Zitat Leach FS et al (1996) Expression of the human mismatch repair gene hMSH2 in normal and neoplastic tissues. Cancer Res 56(2):235–240PubMed Leach FS et al (1996) Expression of the human mismatch repair gene hMSH2 in normal and neoplastic tissues. Cancer Res 56(2):235–240PubMed
60.
Zurück zum Zitat Zhang S, Yu D (2010) PI(3)king apart PTEN’s role in cancer. Clin Cancer Res 16(17):4325–4330PubMed Zhang S, Yu D (2010) PI(3)king apart PTEN’s role in cancer. Clin Cancer Res 16(17):4325–4330PubMed
61.
Zurück zum Zitat Lo YM et al (1997) Presence of fetal DNA in maternal plasma and serum. Lancet 350(9076):485–487PubMed Lo YM et al (1997) Presence of fetal DNA in maternal plasma and serum. Lancet 350(9076):485–487PubMed
62.
Zurück zum Zitat Breveglieri G et al (2019) Non-invasive prenatal testing using fetal DNA. Mol Diagn Ther 23(2):291–299PubMed Breveglieri G et al (2019) Non-invasive prenatal testing using fetal DNA. Mol Diagn Ther 23(2):291–299PubMed
63.
Zurück zum Zitat Haque IS et al (2016) Modeled fetal risk of genetic diseases identified by expanded carrier screening. JAMA 316(7):734–742PubMed Haque IS et al (2016) Modeled fetal risk of genetic diseases identified by expanded carrier screening. JAMA 316(7):734–742PubMed
64.
Zurück zum Zitat Dive L, Newson AJ (2020) Ethical issues in reproductive genetic carrier screening. Med J Aust Dive L, Newson AJ (2020) Ethical issues in reproductive genetic carrier screening. Med J Aust
65.
Zurück zum Zitat Cancer Genome Atlas Network (2012) Comprehensive molecular portraits of human breast tumours. Nature 490(7418):61–70 Cancer Genome Atlas Network (2012) Comprehensive molecular portraits of human breast tumours. Nature 490(7418):61–70
66.
Zurück zum Zitat Mosele F et al (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):1491–1505PubMed Mosele F et al (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):1491–1505PubMed
67.
Zurück zum Zitat Mateo J et al (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):1895–1902PubMedPubMedCentral Mateo J et al (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):1895–1902PubMedPubMedCentral
68.
Zurück zum Zitat Anderson P et al (2008) Real-world physician and patient behaviour across countries: Disease-Specific Programmes - a means to understand. Curr Med Res Opin 24(11):3063–3072PubMed Anderson P et al (2008) Real-world physician and patient behaviour across countries: Disease-Specific Programmes - a means to understand. Curr Med Res Opin 24(11):3063–3072PubMed
69.
Zurück zum Zitat Decker T, Steering Board OPAL, Stickeler E et al (2019) Die klinische Tumorregisterplattform OPAL stellt sich vor. Forum 34:74–76 Decker T, Steering Board OPAL, Stickeler E et al (2019) Die klinische Tumorregisterplattform OPAL stellt sich vor. Forum 34:74–76
70.
Zurück zum Zitat Fasching PA et al (2015) Biomarkers in patients with metastatic breast cancer and the PRAEGNANT study network. Geburtshilfe Frauenheilkd 75(1):41–50PubMedPubMedCentral Fasching PA et al (2015) Biomarkers in patients with metastatic breast cancer and the PRAEGNANT study network. Geburtshilfe Frauenheilkd 75(1):41–50PubMedPubMedCentral
71.
Zurück zum Zitat Perol D et al (2019) The ongoing French metastatic breast cancer (MBC) cohort: the example-based methodology of the epidemiological strategy and medical economics (ESME). BMJ Open 9(2):e23568PubMedPubMedCentral Perol D et al (2019) The ongoing French metastatic breast cancer (MBC) cohort: the example-based methodology of the epidemiological strategy and medical economics (ESME). BMJ Open 9(2):e23568PubMedPubMedCentral
72.
Zurück zum Zitat Quek RGW, Mardekian J (2019) Clinical outcomes, treatment patterns, and health resource utilization among metastatic breast cancer patients with Germline BRCA1/2 mutation: a real-world retrospective study. Adv Ther 36(3):708–720PubMed Quek RGW, Mardekian J (2019) Clinical outcomes, treatment patterns, and health resource utilization among metastatic breast cancer patients with Germline BRCA1/2 mutation: a real-world retrospective study. Adv Ther 36(3):708–720PubMed
73.
Zurück zum Zitat Cardoso F et al (2016) 70-gene signature as an aid to treatment decisions in early-stage breast cancer. N Engl J Med 375(8):717–729PubMed Cardoso F et al (2016) 70-gene signature as an aid to treatment decisions in early-stage breast cancer. N Engl J Med 375(8):717–729PubMed
74.
Zurück zum Zitat Filipits M et al (2019) Prediction of distant recurrence using endopredict among women with ER(+), HER2(-) node-positive and node-negative breast cancer treated with endocrine therapy only. Clin Cancer Res 25(13):3865–3872PubMed Filipits M et al (2019) Prediction of distant recurrence using endopredict among women with ER(+), HER2(-) node-positive and node-negative breast cancer treated with endocrine therapy only. Clin Cancer Res 25(13):3865–3872PubMed
75.
Zurück zum Zitat Kalinsky K et al (2020) SWOG S1007: adjuvant trial randomized ER+ patients who had a Recurrence Score 〈 25 and 1‑3 positive nodes to endocrine therapy (ET) versus ET + chemotherapy. San Antonio Breast Cancer Symposium 2020, S GS3-00 Kalinsky K et al (2020) SWOG S1007: adjuvant trial randomized ER+ patients who had a Recurrence Score 〈 25 and 1‑3 positive nodes to endocrine therapy (ET) versus ET + chemotherapy. San Antonio Breast Cancer Symposium 2020, S GS3-00
76.
Zurück zum Zitat Sparano JA et al (2020) Clinical outcomes in early breast cancer with a high 21-gene recurrence score of 26 to 100 assigned to adjuvant chemotherapy plus endocrine therapy: a secondary analysis of the TAILORx randomized clinical trial. JAMA Oncol 6(3):367–374PubMed Sparano JA et al (2020) Clinical outcomes in early breast cancer with a high 21-gene recurrence score of 26 to 100 assigned to adjuvant chemotherapy plus endocrine therapy: a secondary analysis of the TAILORx randomized clinical trial. JAMA Oncol 6(3):367–374PubMed
77.
Zurück zum Zitat Bundesausschuss, G. (2019) Änderung der Richtlinie Methoden vertragsärztliche Versorgung: Biomarkerbasierte Tests zur Entscheidung für oder gegen eine adjuvante systemische Chemotherapie beim primären Mammakarzinom Bundesausschuss, G. (2019) Änderung der Richtlinie Methoden vertragsärztliche Versorgung: Biomarkerbasierte Tests zur Entscheidung für oder gegen eine adjuvante systemische Chemotherapie beim primären Mammakarzinom
78.
Zurück zum Zitat Gemeinsamer Bundesausschuss (2019) Änderung der Richtlinie Methoden vertragsärztliche Versorgung: Biomarkerbasierte Tests zur Entscheidung für oder gegen eine adjuvante systemische Chemotherapie beim primären Mammakarzinom Gemeinsamer Bundesausschuss (2019) Änderung der Richtlinie Methoden vertragsärztliche Versorgung: Biomarkerbasierte Tests zur Entscheidung für oder gegen eine adjuvante systemische Chemotherapie beim primären Mammakarzinom
79.
Zurück zum Zitat Yamauchi H, Takei J (2018) Management of hereditary breast and ovarian cancer. Int J Clin Oncol 23(1):45–51PubMed Yamauchi H, Takei J (2018) Management of hereditary breast and ovarian cancer. Int J Clin Oncol 23(1):45–51PubMed
80.
Zurück zum Zitat Helleday T (2011) The underlying mechanism for the PARP and BRCA synthetic lethality: clearing up the misunderstandings. Mol Oncol 5(4):387–393PubMedPubMedCentral Helleday T (2011) The underlying mechanism for the PARP and BRCA synthetic lethality: clearing up the misunderstandings. Mol Oncol 5(4):387–393PubMedPubMedCentral
81.
Zurück zum Zitat Murai J et al (2012) Trapping of PARP1 and PARP2 by Clinical PARP Inhibitors. Cancer Res 72(21):5588–5599PubMedPubMedCentral Murai J et al (2012) Trapping of PARP1 and PARP2 by Clinical PARP Inhibitors. Cancer Res 72(21):5588–5599PubMedPubMedCentral
82.
Zurück zum Zitat Litton JK et al (2018) Talazoparib in patients with advanced breast cancer and a Germline BRCA mutation. N Engl J Med 379(8):753–763PubMed Litton JK et al (2018) Talazoparib in patients with advanced breast cancer and a Germline BRCA mutation. N Engl J Med 379(8):753–763PubMed
83.
Zurück zum Zitat Robson ME et al (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):558–566PubMedPubMedCentral Robson ME et al (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):558–566PubMedPubMedCentral
84.
Zurück zum Zitat Fasching PA et al (2021) Neoadjuvant paclitaxel/olaparib in comparison to paclitaxel/carboplatinum in patients with HER2-negative breast cancer and homologous recombination deficiency (GeparOLA study). Ann Oncol 32(1):49–57PubMed Fasching PA et al (2021) Neoadjuvant paclitaxel/olaparib in comparison to paclitaxel/carboplatinum in patients with HER2-negative breast cancer and homologous recombination deficiency (GeparOLA study). Ann Oncol 32(1):49–57PubMed
85.
Zurück zum Zitat Loibl S et al (2018) Survival analysis of carboplatin added to an anthracycline/taxane-based neoadjuvant chemotherapy and HRD score as predictor of response-final results from GeparSixto. Ann Oncol 29(12):2341–2347PubMed Loibl S et al (2018) Survival analysis of carboplatin added to an anthracycline/taxane-based neoadjuvant chemotherapy and HRD score as predictor of response-final results from GeparSixto. Ann Oncol 29(12):2341–2347PubMed
86.
Zurück zum Zitat André F et al (2021) Alpelisib plus fulvestrant for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: final overall survival results from SOLAR‑1. Ann Oncol 32(2):208–217PubMed André F et al (2021) Alpelisib plus fulvestrant for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: final overall survival results from SOLAR‑1. Ann Oncol 32(2):208–217PubMed
87.
Zurück zum Zitat Hoda RS et al (2019) Secretory carcinoma of the breast: clinicopathologic profile of 14 cases emphasising distant metastatic potential. Histopathology 75(2):213–224PubMedPubMedCentral Hoda RS et al (2019) Secretory carcinoma of the breast: clinicopathologic profile of 14 cases emphasising distant metastatic potential. Histopathology 75(2):213–224PubMedPubMedCentral
88.
Zurück zum Zitat Marchio C et al (2019) ESMO recommendations on the standard methods to detect NTRK fusions in daily practice and clinical research. Ann Oncol 30(9):1417–1427PubMed Marchio C et al (2019) ESMO recommendations on the standard methods to detect NTRK fusions in daily practice and clinical research. Ann Oncol 30(9):1417–1427PubMed
89.
Zurück zum Zitat Ross J et al (2018) Abstract P2-09-15: 〈em〉NTRK〈/em〉 fusions in breast cancer: clinical, pathologic and genomic findings. Cancer Res 78(4 Supplement)):P2-09-15 Ross J et al (2018) Abstract P2-09-15: 〈em〉NTRK〈/em〉 fusions in breast cancer: clinical, pathologic and genomic findings. Cancer Res 78(4 Supplement)):P2-09-15
91.
Zurück zum Zitat Jerzak KJ, Mancuso T, Eisen A (2018) Ataxia-telangiectasia gene (ATM) mutation heterozygosity in breast cancer: a narrative review. Curr Oncol 25(2):e176–e180PubMedPubMedCentral Jerzak KJ, Mancuso T, Eisen A (2018) Ataxia-telangiectasia gene (ATM) mutation heterozygosity in breast cancer: a narrative review. Curr Oncol 25(2):e176–e180PubMedPubMedCentral
92.
Zurück zum Zitat Lemery S, Keegan P, Pazdur R (2017) First FDA approval agnostic of cancer site - when a biomarker defines the indication. N Engl J Med 377(15):1409–1412PubMed Lemery S, Keegan P, Pazdur R (2017) First FDA approval agnostic of cancer site - when a biomarker defines the indication. N Engl J Med 377(15):1409–1412PubMed
93.
Zurück zum Zitat Arora S et al (2020) FDA approval summary: pembrolizumab plus lenvatinib for endometrial carcinoma, a collaborative international review under project orbis. Clin Cancer Res 26(19):5062–5067PubMed Arora S et al (2020) FDA approval summary: pembrolizumab plus lenvatinib for endometrial carcinoma, a collaborative international review under project orbis. Clin Cancer Res 26(19):5062–5067PubMed
94.
Zurück zum Zitat Latham A et al (2019) Microsatellite instability is associated with the presence of lynch syndrome pan-cancer. J Clin Oncol 37(4):286–295PubMed Latham A et al (2019) Microsatellite instability is associated with the presence of lynch syndrome pan-cancer. J Clin Oncol 37(4):286–295PubMed
95.
Zurück zum Zitat Schmid P et al (2018) Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med 379(22):2108–2121PubMed Schmid P et al (2018) Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med 379(22):2108–2121PubMed
96.
Zurück zum Zitat Schmid P et al (2020) Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 21(1):44–59PubMed Schmid P et al (2020) Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 21(1):44–59PubMed
97.
Zurück zum Zitat Gonzalez-Angulo AM et al (2011) PI3K pathway mutations and PTEN levels in primary and metastatic breast cancer. Mol Cancer Ther 10(6):1093–1101PubMedPubMedCentral Gonzalez-Angulo AM et al (2011) PI3K pathway mutations and PTEN levels in primary and metastatic breast cancer. Mol Cancer Ther 10(6):1093–1101PubMedPubMedCentral
98.
Zurück zum Zitat Lin NU et al (2012) Clinicopathologic features, patterns of recurrence, and survival among women with triple-negative breast cancer in the National Comprehensive Cancer Network. Cancer 118(22):5463–5472PubMed Lin NU et al (2012) Clinicopathologic features, patterns of recurrence, and survival among women with triple-negative breast cancer in the National Comprehensive Cancer Network. Cancer 118(22):5463–5472PubMed
99.
Zurück zum Zitat Millis SZ et al (2015) Predictive biomarker profiling of 〉 6000 breast cancer patients shows heterogeneity in TNBC, with treatment implications. Clin Breast Cancer 15(6):473–481e3PubMed Millis SZ et al (2015) Predictive biomarker profiling of 〉 6000 breast cancer patients shows heterogeneity in TNBC, with treatment implications. Clin Breast Cancer 15(6):473–481e3PubMed
100.
Zurück zum Zitat Cossu-Rocca P et al (2015) Analysis of PIK3CA mutations and activation pathways in triple negative breast cancer. PLoS ONE 10(11):e141763PubMedPubMedCentral Cossu-Rocca P et al (2015) Analysis of PIK3CA mutations and activation pathways in triple negative breast cancer. PLoS ONE 10(11):e141763PubMedPubMedCentral
101.
Zurück zum Zitat Schuster SC (2008) Next-generation sequencing transforms today’s biology. Nat Methods 5(1):16–18PubMed Schuster SC (2008) Next-generation sequencing transforms today’s biology. Nat Methods 5(1):16–18PubMed
102.
Zurück zum Zitat Nagahashi M et al (2019) Next generation sequencing-based gene panel tests for the management of solid tumors. Cancer Sci 110(1):6–15PubMed Nagahashi M et al (2019) Next generation sequencing-based gene panel tests for the management of solid tumors. Cancer Sci 110(1):6–15PubMed
103.
Zurück zum Zitat Dawson SJ et al (2013) Analysis of circulating tumor DNA to monitor metastatic breast cancer. N Engl J Med 368(13):1199–1209PubMed Dawson SJ et al (2013) Analysis of circulating tumor DNA to monitor metastatic breast cancer. N Engl J Med 368(13):1199–1209PubMed
104.
Zurück zum Zitat Laakmann E et al (2020) Treatment landscape and prognosis after treatment with trastuzumab emtansine. Geburtshilfe Frauenheilkd 80(11):1134–1142PubMedPubMedCentral Laakmann E et al (2020) Treatment landscape and prognosis after treatment with trastuzumab emtansine. Geburtshilfe Frauenheilkd 80(11):1134–1142PubMedPubMedCentral
105.
Zurück zum Zitat Ciani M et al (2019) Genome wide association study and next generation sequencing: a glimmer of light toward new possible horizons in frontotemporal dementia research. Front Neurosci 13:506PubMedPubMedCentral Ciani M et al (2019) Genome wide association study and next generation sequencing: a glimmer of light toward new possible horizons in frontotemporal dementia research. Front Neurosci 13:506PubMedPubMedCentral
Metadaten
Titel
NGS zur Selektion innovativer Therapien – Was bringt das?
verfasst von
Carla E. Schulmeyer
Simon Bader
Hanna Hübner
Matthias Rübner
Prof. Dr. Peter A. Fasching
Publikationsdatum
24.02.2021
Verlag
Springer Medizin
Erschienen in
Die Gynäkologie / Ausgabe 3/2021
Print ISSN: 2731-7102
Elektronische ISSN: 2731-7110
DOI
https://doi.org/10.1007/s00129-021-04774-9

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