Diagnosis and Therapy of Triple-Negative Breast Cancer (TNBC) – Recommendations for Daily Routine Practice

Andreas Schneeweiss; Carsten Denkert; Peter A. Fasching; Carlo Fremd; Oleg Gluz; Cornelia Kolberg-Liedtke; Sibylle Loibl; Hans-Joachim Lück

doi:10.1055/a-0887-0285

Geburtshilfe und Frauenheilkunde, Inhaltsverzeichnis

CC BY-NC-ND 4.0 · Geburtshilfe Frauenheilkd 2019; 79(06): 605-617
DOI: 10.1055/a-0887-0285

GebFra Science

Review/Übersicht

Georg Thieme Verlag KG Stuttgart · New York

Diagnostik und Therapie des triple-negativen Mammakarzinoms (TNBC) – Empfehlungen für die tägliche Routine

Artikel in mehreren Sprachen: English | deutsch

Autoren

Andreas Schneeweiss

¹Nationales Centrum für Tumorerkrankungen (NCT), Universitätsklinikum, Heidelberg, Germany

²Deutsches Krebsforschungszentrum, Heidelberg, Germany
Carsten Denkert

³Institut für Pathologie, Universitätsklinikum Gießen und Marburg GmbH, Standort Marburg, Philipps-Universität Marburg, Marburg, Germany
Peter A. Fasching

⁴Frauenklinik des Universitätsklinikums Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany
Carlo Fremd

¹Nationales Centrum für Tumorerkrankungen (NCT), Universitätsklinikum, Heidelberg, Germany
Oleg Gluz

⁵Brustzentrum Niederrhein, Evangelisches Krankenhaus Bethesda, Mönchengladbach, Germany

⁶Westdeutsche Studiengruppe, Mönchengladbach, Germany
Cornelia Kolberg-Liedtke

⁷Charité – Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany
Sibylle Loibl

⁸German Breast Group c/o GBG Forschungs GmbH, Neu-Isenburg, Germany

⁹Zentrum für Hämatologie und Onkologie Bethanien, Goethe Universität Frankfurt, Frankfurt am Main, Germany
Hans-Joachim Lück

¹⁰Gynäkologie Onkologie, Gynäkologisch-onkologische Praxis, Hannover, Germany

Abstract

Zusammenfassung

Durch den raschen Erkenntnisgewinn zu Tumorbiologie und Tumorpathogenese des triple-negativen Mammakarzinoms (TNBC) ergeben sich neue Therapieansätze und neue Therapiekonzepte für die Behandlung. Seit Jahren gilt das TNBC wegen seiner in der Regel aggressiven Tumorbiologie und angesichts limitierter Therapieoptionen als schwierig zu behandelnder Tumor. Das Rezidiv- und Metastasierungsrisiko ist höher als bei anderen Mammakarzinom-Subtypen desselben Stadiums. Neben Operation und Bestrahlung in der kurativen Situation ist die systemische Chemotherapie mit Anthrazyklinen und/oder Taxanen nach wie vor die Therapie der Wahl. Neue Therapieansätze basieren auf der Erkenntnis, dass das TNBC eine molekular sehr heterogene Erkrankung ist. Forschungsgruppen arbeiten daran, das TNBC immer besser auf molekularer Ebene zu klassifizieren und diese molekulare Subtypisierung als Grundlage für neue therapeutische Strategien zu nutzen. Im Folgenden werden die vielversprechendsten neuen Ansätze und Überlegungen zur Therapie des TNBCs dargestellt. Anhand einer fiktiven Kasuistik werden zudem die derzeitigen Therapiestrategien unter Berücksichtigung der aktuellen Datenlage und den sich daraus ergebenden therapeutischen Konsequenz besprochen.

Schlüsselwörter

triple-negatives Mammakarzinom - BRCA-Mutation - Subtypisierung des TNBC - Diagnostik und Therapie des TNBC

Volltext

Referenzen

References/Literatur
1 Zeichner SB, Ambros T, Zaravinos J. et al. Defining the survival benchmark for breast cancer patients with systemic relapse. Breast Cancer (Auckl) 2015; 9: 9-17
2 Zeichner SB, Herna S, Mani A. et al. Survival of patients with de-novo metastatic breast cancer: analysis of data from a large breast cancer-specific private practise, a university-based cancer center and review of the literature. Breast Cancer Res Treat 2015; 153: 617-624
3 Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) Kommission ‚Mamma‘ (vertreten durch Wolfgang Janni). Diagnose und Behandlung von Patienten mit primärem und metastasiertem Mammakarzinom. Version 2019 v1. München: W. Zuckschwerdt; 2019. Online: www.ago-online.de last access: 27.03.2019
4 Mersin H, Yildirim E, Berberoglu U. et al. The prognostic importance of triple negative breast carcinoma. Breast 2008; 17: 341-346
5 Dawood S, Lei X, Litton JK. et al. Incidence of brain metastases as a first site of recurrence among women with triple negative breast cancer. Cancer 2012; 118: 4652-4659
6 Lin NU, Vanderplas A, Hughes ME. et al. Clinicopathologic features, patterns of recurrence, and survival among women with triple negative breast cancer in the National Comprehensive cancer Network. Cancer 2012; 118: 5463
7 Leitlinienprogramm Onkologie (Deutsche Krebsgesellschaft, Deutsche Krebshilfe, AWMF). Interdisziplinäre S3-Leitlinie für die Früherkennung, Diagnostik, Therapie und Nachsorge des Mammakarzinoms, Langversion 4.0. Dezember 2017. AWMF Registernummer: 032-045OL. Online: http://www.leitlinienprogramm-onkologie.de/leitlinien/mammakarzinom/ last access: 08.10.2018
8 Wöckel A, Festl J, Stüber T. et al. Interdisciplinary Screening, Diagnosis, Therapy and Follow-up of Breast Cancer. Guideline of the DGGG and the DKG (S3-Level, AWMF Registry Number 032/045OL, December 2017) – Part 1 with Recommendations for the Screening, Diagnosis and Therapy of Breast Cancer. Geburtsh Frauenheilk 2018; 78: 927-948
9 Häberle L, Hein A, Rübner M. et al. Predicting Triple-Negative Breast Cancer Subtype Using Multiple Single Nucleotide Polymorphisms for Breast Cancer Risk and Several Variable Selection Methods. Geburtsh Frauenheilk 2017; 77: 667-678
10 Stevens KN, Fredericksen Z, Vachon CM. et al. 19p13.1 is a triple-negative-specific breast cancer susceptibility locus. Cancer Res 2012; 72: 1795-1803
11 Purrington KS, Slager S, Eccles D. et al. Genome-wide association study identifies 25 known breast cancer susceptibility loci as risk factors for triple-negative breast cancer. Carcinogenesis 2012; 35: 1012-1019
12 Lehmann BD, Bauer JA, Chen X. et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest 2011; 121: 2750-2767
13 Lehmann BC, Jovanovic B, Chen X. et al. Refinement of Triple-Negative Breast Cancer Molecular Subtypes: Implications for Neoadjuvant Chemotherapy Selection. PLoS One 2016; 11: e0157368 doi:10.13717/journal.pone.0157368
14 Kreike B, van Kouwenhove M, Horlings H. et al. Gene expression profiling and histopathological characterization of triple-negative/basal-like breast carcinomas. Breast Cancer Res 2007; 9: R65
15 Burstein MD, Tsimelzon A, Poage GM. et al. Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer. Clin Cancer Res 2015; 21: 1688-1698
16 Jézéquel P, Loussouarn D, Guérin-Charbonnel C. et al. Gene-expression molecular subtyping of triple-negative breast cancer tumours. Importance of immune response. Breast Cancer Res 2015; 17: 43
17 Liedtke C, Mazouni C, Hess KR. et al. Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol 2008; 26: 1275-1281
18 Schneeweiss A, Jackisch C, Schmatloch S. et al. Survival analysis of the prospectively randomized phase III GeparSepto trial comparing neoadjuvant chemotherapy with weekly nab-paclitaxel with solvent-based paclitaxel followed by anthracycline/cyclophosphamide for patients with early breast cancer – GBG 69. SABCS 2017; Abstr. GS3-05.
19 Cortazar P, Zhang L, Untch M. et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet 2014; 384: 164-172
20 Marty B, Maire V, Gravier E. et al. Frequent PTEN genomic alterations and activated phosphatidylinositol 3-kinase pathway in basal-like breast cancer cells. Breast Cancer Res 2008; 10: R101
21 Schmid P, Abraham J, Chan S. et al. AZD5363 plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer (PAKT): A randomised, double-blind, placebo-controlled, phase II trial. J Clin Oncol 2018; 36 (no.15_suppl): 1007-1007 doi:10.1200/JCO.2018.36.15_suppl.1007
22 Dent R, Im SA, Espie M. et al. Overall survival update of the double-blind placebo-controlled randomised phase 2 LOTUS trial of first-line Ipataserib + paclitaxel for locally advanced/metastatic triple-negative breast cancer. J Clin Oncol 2018; 36 (no.15_suppl): 1008 doi:10.1200/JCO.2018.36.15_suppl.1008
23 Harrison H, Farnie G, Howell SJ. et al. Regulation of breast cancer stem cell activity by signaling through the Notch4 receptor. Cancer Res 2010; 70: 709-718
24 Stoeck A, Lejnine S, Truong A. et al. Discovery of biomarkers predictive of GSI response in triple-negative breast cancer and adenoid cystic carcinoma. Cancer Discov 2014; 4: 1154-1167
25 Balko JM, Giltnane JM, Wang K. et al. Molecular profiling of the residual disease of triple-negative breast cancers after neoadjuvant chemotherapy identifies actionable therapeutic targets. Cancer Discov 2014; 4: 232-245
26 Baselga J, Gomez P, Greil R. et al. Randomized phase II study of the anti-epidermal growth factor receptor monoclonal antibody cetuximab with cisplatin versus cisplatin alone in patients with metastatic triple-negative breast cancer. J Clin Oncol 2013; 31: 2586-2592
27 Carey LA, Rugo HS, Marcom PK. et al. TBCRC 001: randomized phase II study of cetuximab in combination with carboplatin in stage IV triple-negative breast cancer. J Clin Oncol 2012; 30: 2615-2623
28 Brufsky A, Valero V, Tiango B. et al. Second-line bevacizumab-containing therapy in patients with triple-negative breast cancer: subgroup analysis of the RIBBON-2 trial. Breast Cancer Res Treat 2012; 133: 1067-1075
29 Turner N, Lambros MB, Horlings HM. et al. Integrative molecular profiling of triple negative breast cancers identifies amplicon drivers and potential therapeutic targets. Oncogene 2010; 29: 2013-2023
30 Sharpe R, Pearson A, Herrera-Abreu MT. et al. FGFR signaling promotes the growth of triple-negative and basal-like breast cancer cell lines both in vitro and in vivo. Clin Cancer Res 2011; 17: 5275-5286
31 Niemeier LA, Dabbs DJ, Beriwal S. et al. Androgen receptor in breast cancer: expression in estrogen receptor-positive tumors and in estrogen receptor-negative tumors with apocrine differentiation. Mod Pathol 2010; 23: 205-212
32 Traina TA, Miller K, Yardley DA. et al. Enzalutamide for the Treatment of Androgen Receptor-Expressing Triple-Negative Breast Cancer. J Clin Oncol 2018; 36: 884-890
33 Yamaoka M, Hara T, Hitaka T. et al. Orteronel (TAK-700), a novel non-steroidal 17,20-lyase inhibitor: effects on steroid synthesis in human and monkey adrenal cells and serum steroid levels in cynomolgus monkeys. J Steroid Biochem Mol Biol 2012; 129: 115-128
34 Stepan LP, Trueblood ES, Hale K. et al. Expression of Trop2 cell surface glycoprotein in normal and tumor tissues: potential implications as a cancer therapeutic target. J Histochem Cytochem 2011; 59: 701-710
35 Ambrogi F, Fornili M, Boracchi P. et al. Trop2 is a determinant of breast cancer survival. PLoS One 2014; 9: e96993
36 Bardia A, Starodub A, Moroose RL. et al. IMMUN-132, a new antibody-drug-conjugate against Trop2, as a novel therapeutic for patients with relapsed/refractory, metastatic, triple-negative breast cancer: results from phase I/II clinical trial (NCT01631552). 37th San Antonio Breast Cancer Symposium (SABCS) 2014; P5-19-27.
37 ClinicalTrials.gov Identifier: NCT02574455.
38 Emens LA, Kok M, Ojalvo LS. et al. Targeting the programmed cell death-1 pathway in breast and ovarian cancer. Curr Opin Obstet Gynecol 2016; 28: 142-147
39 Gao R, Davis A, McDonald TO. et al. Punctuated copy number evolution and clonal stasis in triple-negative breast cancer. Nat Genet 2016; 48: 1119-1130
40 Pruneri G, Vingiani A, Bagnardi V. et al. Clinical validity of tumor-infiltrating lymphocytes analysis in patients with triple-negative breast cancer. Ann Oncol 2016; 27: 249-256
41 Pruneri G, Vingiani A, Denkert C. Tumor infiltrating lymphocytes in early breast cancer. The Breast 2018; 37: 207e214 doi:10.1016/j.breast.2017.03.010
42 Loi S, Michiels S, Salgado R. et al. Tumor infiltrating lymphocytes are prognostic in triple negative breast cancer and predictive for trastuzumab benefit in early breast cancer: results from the FinHER Trial. Ann Oncol 2014; 25: 1544-1550
43 Adams S, Gray RJ, Demaria S. et al. Prognostic Value of Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer From Two Phase III Randomized Adjuvant Breast Cancer Trials: ECOG 2197 and ECOG 1199. J Clin Oncol 2014; 32: 2959-2966
44 Denkert C, von Minckwitz G, Brase JC. et al. Tumor-infiltrating lymphocytes and response to neoadjuvant chemotherapy with and without carboplatin in human epidermal growth factor receptor 1-positive and triple-negative primary breast cancers. J Clin Oncol 2015; 33: 983-991
45 Würfel F, Erber R, Huebner H. et al. TILGen: A Program to Investigate Immune Targets in Breast Cancer Patients – First Results on the Influence of Tumor-Infiltrating Lymphocytes. Breast Care (Basel) 2018; 13: 8-14
46 Denkert C, von Minckwitz G, Darb-Esfahani S. et al. Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy. Lancet Oncol 2018; 19: 40-50
47 Mayer IA, Abramson VG, Lehmann BD. et al. New strategies for triple-negative cancer – deciphering the heterogeneity. Clin Cancer Res 2014; 20: 787-790
48 Loibl S, Untch M, Burchardi N. et al. Randomized phase II neoadjuvant study (GeparNuevo) to investigate the addition of durvalumab to a taxane-anthracycline containing chemotherapy in triple negative breast cancer. ASCO J Clin Oncol 2018; 36 (Suppl.) Abstr. 104
49 Schmid P, Adams S, Rugo HS. et al. Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. N Engl J Med 2018; 379: 2108-2121
50 Emens LA, Loi S, Rugo HS. et al. Impassion130: Efficacy in immune biomarker subgroups from the global, randomized, double-blind, placebo-controlled, Phase III study of Atezolizumab + nab-paclitaxel in patients with treatment-naïve, locally advanced or metastatic triple-negative breast cancer. SABCS 2018; abstract/oral presentation GS1-04.
51 Hahnen E, Lederer B, Hauke J. et al. Germline Mutation Status, Pathological Complete Response, and Disease-free Survival in Triple-Negative Breast Cancer: Secondary Analysis of the GeparSixto Randomized Clinical Trial. JAMA Oncol 2017; 3: 1378-1385
52 Couch FJ, Hart SN, Sharma P. et al. Inherited mutations in 17 breast cancer susceptibility genes among a large triple-negative breast cancer cohort unselected for family history of breast cancer. J Clin Oncol 2015; 33: 304-311
53 Fasching PA, Loibl S, Hu C. et al. BRCA1/2 Mutations and Bevacizumab in the Neoadjuvant Treatment of Breast Cancer: Response and Prognosis Results in Patients With Triple-Negative Breast Cancer From the GeparQuinto Study. J Clin Oncol 2018; 36: 2281-2287
54 Lord CJ, Ashworth A. BRCAness revisited. Nat Rev Cancer 2016; 16: 110-120
55 Telli ML, Timms KM, Reid J. et al. Homologous Recombination Deficiency (HRD) Score Predicts Response to Platinum-Containing Neoadjuvant Chemotherapy in Patients with Triple-Negative Breast Cancer. Clin Cancer Res 2016; 22: 3764-3773
56 Loibl S, Weber KE, Timms KM. et al. 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 2018;
57 Copson ER, Maishman TC, Tapper WJ. et al. Germline BRCA mutation and outcome in young-onset breast cancer (POSH). A prospective cohort study. Lancet Oncol 2018; 19: 169-180
58 Tutt A, Tovey H, Cheang MCU. et al. Carboplatin in BRCA1/2-mutated and triple-negative breast cancer BRCAness subgroups: the TNT Trial. Nature Medicine 2018; 24: 628-637
59 Rodler ET, Kurland BR, Griffin M. et al. Phase I Study of Veliparib Combined with Cisplatin and Vinorelbine in Advanced Triple-Negative Breast Cancer and/or BRCA Mutation-Associated Breast Cancer. Clin Cancer Res 2016; 22: 2855-2864
60 Robson M, Im SA, Senkus E. et al. Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation. N Engl J Med 2017; 377: 523-533
61 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
62 Loibl S, OʼShaughnessy J, Untch M. et al. Addition of the PARP inhibitor veliparib plus carboplatin or carboplatin alone to standard neoadjuvant chemotherapy in triple-negative breast cancer (BrighTNess). A randomised, phase 3 trial. Lancet Oncol 2018; 19: 497-509
63 Denkert C, Loibl S, Müller BM. et al. Ki67 levels as predictive and prognostic parameters in pretherapeutic breast cancer core biopsies: a translational investigation in the neoadjuvant GeparTrio trial. Ann Oncol 2013; 24: 2786-2793
64 Gray R, Bradley R, Braybrooke J. et al. Increasing the dose density of adjuvant chemotherapy by shortening intervals between courses or by sequential drug administration significantly reduces both disease recurrence and breast cancer mortality: An EBCTCG meta-analysis. SABCS 2017; Abstr. GS1-01.
65 Moebus V, Jackisch C, Lück HJ. et al. Ten-year results of intense dose-dense chemotherapy show superior survival compared with a conventional schedule in high-risk primary breast cancer: final results of AGO phase III iddEPC trial. Ann Oncol 2018; 29: 178-185
66 Sparano JA, Wang M, Martino S. et al. Weekly paclitaxel in the adjuvant treatment of breast cancer. N Engl J Med 2008; 358: 1663-1671
67 Sparano JA, Zhao F, Martino S. et al. Long-Term Follow-Up of the E1199 Phase III Trial Evaluating the Role of Taxane and Schedule in Operable Breast Cancer. J Clin Oncol 2015; 33: 2353-2360
68 von Minckwitz G, Schneeweiss A, Loibl S. et al. Neoadjuvant carboplatin in patients with triple-negative and HER2-positive early breast cancer (GeparSixto; GBG 66): a randomised phase 2 trial. Lancet Oncol 2014; 15: 747-756
69 Sikov WM, Berry DA, Perou CM. et al. Impact of the Addition of Carboplatin and/or Bevacizumab to Neoadjuvant Once-per-Week Paclitaxel Followed by Dose-Dense Doxorubicin and Cyclophosphamide on Pathologic Complete Response Rates in Stage II to III Triple-Negative Breast Cancer: CALGB 40603 (Alliance). J Clin Oncol 2015; 33: 13-21
70 Schneeweiss A, Möbus V, Tesch H. et al. Intense dose-dense epirubicin, paclitaxel, cyclophosphamide versus weekly paclitaxel, liposomal doxorubicin (plus carboplatin in triple-negative breast cancer) for neoadjuvant treatment of high-risk early breast cancer (GeparOcto-GBG 84): A randomised phase III trial. Eur J Cancer 2018; 106: 181-192
71 von Minckwitz G, Untch M, Blohmer JU. et al. Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol 2012; 30: 1796-1804
72 Berruti A, Amoroso V, Gallo F. et al. Pathologic complete response as a potential surrogate for the clinical outcome in patients with breast cancer after neoadjuvant therapy. A metaanalysis of 29 randomized prospective studies. J Clin Oncol 2014; 32: 3883-3891
73 Symmans WF, Wei C, Gould R. et al. Long-Term Prognostic Risk After Neoadjuvant Chemotherapy Associated With Residual Cancer Burden and Breast Cancer Subtype. J Clin Oncol 2017; 35: 1049-1060
74 Masuda N, Lee S-J, Ohtani S. et al. Adjuvant Capecitabine for Breast Cancer after Preoperative Chemotherapy. N Engl J Med 2017; 376: 2147-2156
75 Zujewski JA, Rubinstein L. CREATE-X a role for capecitabine in early-stage breast cancer: an analysis of available data. NPJ Breast Cancer 2017; 3: 27
76 Untch M, Jackisch C, Schneeweiss A. et al. Nab-paclitaxel versus solvent-based paclitaxel in neoadjuvant chemotherapy for early breast cancer (GeparSepto-GBG 69): a randomised, phase 3 trial. Lancet Oncol 2016; 17: 345-356
77 von Minckwitz G. Early survival analysis of the randomised phase II trial investigating the addition of carboplatin to neoadjuvant therapy for triple-negative and HER2-positive early breast cancer (GeparSixto). SABCS2015; Abstr. S2-04.
78 Petrelli F, Coinu A, Borgonovo K. et al. The value of platinum agents as neoadjuvant chemotherapy in triple-negative breast cancers: a systematic review and meta-analysis. Breast Cancer Res Treat 2014; 144: 223-232
79 Wunderle M, Gass P, Häberle L. et al. BRCA mutations and their influence on pathological complete response and prognosis in a clinical cohort of neoadjuvantly treated breast cancer patients. Breast Cancer Res Treat 2018; 171: 85-94
80 Paluch-Shimon S, Friedman E, Berger R. et al. Neo-adjuvant doxorubicin and cyclophosphamide followed by paclitaxel in triple-negative breast cancer among BRCA1 mutation carriers and non-carriers. Breast Cancer Res Treat 2016; 157: 157-165
81 Gluz O, Nitz U, Liedtke C. et al. Comparison of Neoadjuvant Nab-Paclitaxel+Carboplatin vs Nab-Paclitaxel+Gemcitabine in Triple-Negative Breast Cancer: Randomized WSG-ADAPT-TN Trial Results. J Natl Cancer Inst 2018; 110: 628-637
82 Gluz O, Nitz U, Liedtke C. et al. Prognostic impact of anthracyclines and immune/proliferation markers in TNBC according to pCR after de-escalated neoadjuvant chemotherapy with 12 weeks og nab-paclitaxel/carboplatin or gemcitabine: Survival results of WSG-ADAPT-TN phase II trial. ESMO 2018; München, Poster.
83 National Comprehensive Cancer Network (NCCN). Breast Cancer. Online: https://www.nccn.org/professionals/physician_gls/default.aspx last access: 15.01.2019
84 Therapieempfehlungen der Amerikanischen Gesellschaft für klinische Onkologie (ASCO). Online: https://www.asco.org/practice-guidelines/quality-guidelines/guidelines/breast-cancer European Society for medical oncology; last access: 15.01.2019
85 ESMO. International Consensus Guidelines for Advanced Breast Cancer (ABC3). Online: https://www.esmo.org/Guidelines/Breast-Cancer last access: 15.01.2019 oder: Cardoso F, Costa A, Senkus E. et al. 3rd ESO-ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC3). Ann Oncol 2017; 28: 16-33 doi:10.1093/annonc/mdw544
86 Wapnir IR, Price KN, Anderson SJ. et al. Efficacy of Chemotherapy for ER-Negative and ER-Positive Isolated Locoregional Recurrence of Breast Cancer. Final Analysis of the CALOR Trial. N Engl J Med 2018; 36: 1073-1079
87 Coombe R, Lisy K, Campbell J. et al. Survival outcomes following aggressive treatment of oligometastatic breast cancer: a systematic review protocol. JBI Database System Rev Implement Rep 2017; 15: 2013-2019
88 Rugo HS, Barry WT, Moreno-Aspitia A. et al. Randomized phase III trial of paclitaxel once per week compared with nanoparticle albumin-bound nab-paclitaxel once per week or ixabepilone with bevacizumab as first-line chemotherapy for locally recurrent or metastatic breast cancer: CALGB 40502/NCCTG N063H (alliance). J Clin Oncol 2015; 33: 2361-2369
89 Hamilton E, Kimmick G, Hopkins J. et al. Nab-paclitaxel/bevacizumab/carboplatin chemotherapy in first-line triple negative metastatic breast cancer. Clin Breast Cancer 2013; 13: 416-420
90 Lobo C, Lopes G, Baez O. et al. Final results of a phase II study of nab-paclitaxel, bevacizumab and gemcitabine as first-line therapy for patients with HER2-negative metastatic breast cancer. Breast Cancer Res Treat 2010; 123: 427-435
91 Yardley DA, Coleman R, Conte P. et al. nab-Paclitaxel plus carboplatin or gemcitabine versus gemcitabine plus carboplatin as first-line treatment of patients with triple-negative metastatic breast cancer: results from the tnAcity trial. Ann Oncol 2018; 29: 1763-1770
92 Fachinformation Abraxane^® 5 mg/ml, Stand: Juli 2018.
93 Dent R, Andre F, Goncalves A. et al. IMpassion132: A double-blind randomized phase 3 trial evaluating chemotherapy (CT) ± atezolizumab (atezo) for early progressing locally advanced/metastatic triple-negative breast cancer (mTNBC). ASCO J Clin Oncol 2018; 36 (Suppl.) TPS1115
94 ClinicalTrials.gov Identifier: NCT02620280.
95 Online: https://www.gbg.de/de/studien/gepardouze.php last access: 20.01.2019
96 ClinicalTrials.gov Identifier: NCT01997333.
97 Stirrups R. Sacituzumab govitecan-hziy for triple-negative breast cancer. Lancet Oncol 2019; pii:S1470-2045(19)30074-9 doi:10.1016/S1470-2045(19)30074-9
98 Bardia A, Mayer IA, Vahdat LT. et al. Sacituzumab Govitecan-hiziy in Refractory Metastatic Triple-Negative Breast Cancer. N Engl J Med 2019; 380: 741-751
99 ClinicalTrials.gov Identifier: NCT02338167.
100 Fasching PA, Brucker SY, Fehm TN. et al. Biomarkers in Patients with Metastatic Breast Cancer and the PRAEGNANT Study Network. Geburtsh Frauenheilk 2015; 75: 41-50
101 Online: http://www.gbg.de/de/Studien/aurora.php last access: 20.01.2019