Update Mammakarzinom 2019 Teil 1 – Implementierung der Ergebnisse neuer Studienkonzepte beim frühen Mammakarzinom in die klinische Praxis

Andreas D. Hartkopf; Volkmar Müller; Achim Wöckel; Michael P. Lux; Wolfgang Janni; Naiba Nabieva; Florin-Andrei Taran; Johannes Ettl; Diana Lüftner; Erik Belleville; Florian Schütz; Peter A. Fasching; Tanja N. Fehm; Hans-Christian Kolberg; Friedrich Overkamp; Andreas Schneeweiss; Hans Tesch

doi:10.1055/a-0869-8819

Senologie - Zeitschrift für Mammadiagnostik und -therapie, Table of Contents

Senologie - Zeitschrift für Mammadiagnostik und -therapie 2019; 16(01): 33-44
DOI: 10.1055/a-0869-8819

Wissenschaftliche Arbeit

Update Mammakarzinom 2019 Teil 1 – Implementierung der Ergebnisse neuer Studienkonzepte beim frühen Mammakarzinom in die klinische Praxis

Update breast cancer 2019 part 1 – implementation of study results of novel study designs in clinical practice in patients with early breast cancer

Andreas D. Hartkopf

¹Department of Obstetrics and Gynecology, University of Tübingen, Tübingen

,

Volkmar Müller

²Department of Gynecology, Hamburg-Eppendorf University Medical Center, Hamburg

,

Achim Wöckel

³Department of Gynecology and Obstetrics, University Hospital Würzburg, Würzburg

,

Michael P. Lux

⁴Erlangen University Hospital, Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen

,

Wolfgang Janni

⁵Department of Gynecology and Obstetrics, Ulm University Hospital, Ulm

,

Naiba Nabieva

⁴Erlangen University Hospital, Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen

,

Florin-Andrei Taran

¹Department of Obstetrics and Gynecology, University of Tübingen, Tübingen

,

Johannes Ettl

⁶Department of Obstetrics and Gynecology, Klinikum rechts der Isar, Technical University of Munich, Munich

,

Diana Lüftner

⁷Charité University Hospital, Campus Benjamin Franklin, Department of Hematology, Oncology and Tumour Immunology, Berlin

,

Erik Belleville

⁸ClinSol GmbH & Co. KG, Würzburg

,

Florian Schütz

⁹Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg

,

Peter A. Fasching

⁴Erlangen University Hospital, Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen

,

Tanja N. Fehm

¹⁰Department of Gynecology and Obstetrics, University Hospital Düsseldorf, Düsseldorf

,

Hans-Christian Kolberg

¹¹Department of Gynecology and Obstetrics, Marienhospital Bottrop, Bottrop

,

Friedrich Overkamp

¹²OncoConsult Hamburg GmbH, Hamburg

,

Andreas Schneeweiss

¹³National Center for Tumor Diseases, Division Gynecologic Oncology, University Hospital Heidelberg, Heidelberg

,

Hans Tesch

¹⁴Oncology Practice at Bethanien Hospital Frankfurt, Frankfurt

› Author Affiliations

Abstract

Zusammenfassung

In der Prävention und Behandlung des frühen Mammakarzinoms sind über die Jahre immer wieder kleine, aber bedeutsame Fortschritte gemacht worden. In der Prävention gewinnen die sogenannten Panel-Gen-Analysen immer mehr an Bedeutung, da das durch die getesteten Gene bedingte Risiko immer besser verstanden wird und somit Konzepte für die Integration in die Krankenversorgung erarbeitet werden können. In der adjuvanten Situation konnte die erste Studie in der sogenannten postneoadjuvanten Situation bei fehlender pathologischer Komplettremission nach Trastuzumab oder Pertuzumab + Trastuzumab eine deutliche Verbesserung der Prognose zeigen. Weitere Studien mit diesem postneoadjuvanten Therapiekonzept werden zurzeit noch durchgeführt. Die CDK4/6-Inhibitoren, die in der metastasierten Situation eine deutliche Verbesserung des progressionsfreien Überlebens gezeigt hatten, werden zurzeit in der adjuvanten Situation in großen Therapiestudien getestet. Diese und weitere neue Daten zur Behandlung oder Prävention des primären Mammakarzinoms werden in dieser Übersichtsarbeit vor dem Hintergrund aktueller Studien vorgestellt.

Abstract

For many years, small but significant advancements have been made time and again in the prevention and treatment of early breast cancer. The so-called panel gene analyses are becoming more and more important in prevention, since the risk due to the tested genes is better understood and as a result, concepts for integration in health care can be developed. In the adjuvant situation, the first study in the so-called postneoadjuvant situation was able to demonstrate a clear improvement in the prognosis with an absent pathological complete remission following trastuzumab or pertuzumab + trastuzumab. Additional studies with this post-neoadjuvant therapeutic concept are still being conducted at present. The CDK4/6 inhibitors which had shown a significant improvement in progression-free survival in a metastatic situation are currently being tested in the adjuvant situation in large therapeutic studies. These and other new data for the treatment or prevention of primary breast cancer are presented in this review against the backdrop of current studies.

Schlüsselwörter

Frühes Mammakarzinom - adjuvante Therapie - neoadjuvante Therapie - T‑DM1 - Katherine - Prävention

Key words

early breast cancer - adjuvant therapy - neoadjuvant therapy - T‑DM1 - Katherine - prevention

Full Text

References

Literatur
1 Brennan M, Gass P, Haberle L. et al. The effect of participation in neoadjuvant clinical trials on outcomes in patients with early breast cancer. Breast Cancer Res Treat 2018;
2 Hennigs A, Riedel F, Marme F. et al. Changes in chemotherapy usage and outcome of early breast cancer patients in the last decade. Breast Cancer Res Treat 2016; 160: 491-499
3 Kreienberg R, Wockel A, Wischnewsky M. Highly significant improvement in guideline adherence, relapse-free and overall survival in breast cancer patients when treated at certified breast cancer centres: An evaluation of 8323 patients. Breast 2018; 40: 54-59
4 Beckmann MW, Brucker C, Hanf V. et al. Quality assured health care in certified breast centers and improvement of the prognosis of breast cancer patients. Onkologie 2011; 34: 362-367
5 Early Breast Cancer Trialistsʼ Collaborative Group. Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials. Lancet 2015; 386: 1353-1361
6 Early Breast Cancer Trialistsʼ Collaborative Group. Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials. Lancet 2015; 386: 1341-1352
7 Early Breast Cancer Trialistsʼ Collaborative Group (EBCTCG). Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100 000 women in 123 randomised trials. Lancet 2012; 379: 432-444
8 Wunderle M, Olmes G, Nabieva N. et al. Risk, Prediction and Prevention of Hereditary Breast Cancer – Large-Scale Genomic Studies in Times of Big and Smart Data. Geburtsh Frauenheilk 2018; 78: 481-492
9 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
10 Fasching PA, Ekici AB, Adamietz BR. et al. Breast Cancer Risk – Genes, Environment and Clinics. Geburtsh Frauenheilk 2011; 71: 1056-1066
11 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;
12 Couch FJ, Shimelis H, Hu C. et al. Associations Between Cancer Predisposition Testing Panel Genes and Breast Cancer. JAMA Oncol 2017; 3: 1190-1196
13 Kraus C, Hoyer J, Vasileiou G. et al. Gene panel sequencing in familial breast/ovarian cancer patients identifies multiple novel mutations also in genes others than BRCA1/2. Int J Cancer 2017; 140: 95-102
14 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
15 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
16 Fasching PA, Hu C, Hart SN. et al. Cancer predisposition genes in metastatic breast cancer – Association with metastatic pattern, prognosis, patient and tumor characteristics [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5–9; San Antonio, TX Philadelphia (PA): AACR. Cancer Res 2018 Abstr. PD1-02 78.
17 Hoyer J, Vasileiou G, Uebe S. et al. Addition of triple negativity of breast cancer as an indicator for germline mutations in predisposing genes increases sensitivity of clinical selection criteria. BMC Cancer 2018; 18: 926
18 Antoniou AC, Casadei S, Heikkinen T. et al. Breast-cancer risk in families with mutations in PALB2. N Engl J Med 2014; 371: 497-506
19 Couch FJ, Hu C, Hart SN. et al. Age-related breast cancer risk estimates for the general population based on sequencing of cancer predisposition genes in 19228 breast cancer patients and 20211 matched unaffected controls from US based cohorts in the CARRIERS study. San Antonio Breast Cancer Symposium 2018 Abstr. GS2-01
20 Fasching PA, Schneeweiss A, Kolberg HC. et al. Translational highlights in breast cancer research and treatment: recent developments with clinical impact. Curr Opin Obstet Gynecol 2019; 31: 67-75
21 Ghoussaini M, Fletcher O, Michailidou K. et al. Genome-wide association analysis identifies three new breast cancer susceptibility loci. Nat Genet 2012; 44: 312-318
22 Garcia-Closas M, Couch FJ, Lindstrom S. et al. Genome-wide association studies identify four ER negative-specific breast cancer risk loci. Nat Genet 2013; 45: 392-398 , 398e1–398e2
23 French JD, Ghoussaini M, Edwards SL. et al. Functional variants at the 11q13 risk locus for breast cancer regulate cyclin D1 expression through long-range enhancers. Am J Hum Genet 2013; 92: 489-503
24 Bojesen SE, Pooley KA, Johnatty SE. et al. Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer. Nat Genet 2013; 45: 371-384 , 384e1–384e2
25 Michailidou K, Beesley J, Lindstrom S. et al. Genome-wide association analysis of more than 120000 individuals identifies 15 new susceptibility loci for breast cancer. Nat Genet 2015; 47: 373-380
26 Michailidou K, Hall P, Gonzalez-Neira A. et al. Large-scale genotyping identifies 41 new loci associated with breast cancer risk. Nat Genet 2013; 45: 353-361 , 361e1–361e2
27 Michailidou K, Lindstrom S, Dennis J. et al. Association analysis identifies 65 new breast cancer risk loci. Nature 2017; 551: 92-94
28 Mavaddat N, Pharoah PD, Michailidou K. et al. Prediction of breast cancer risk based on profiling with common genetic variants. J Natl Cancer Inst 2015; 107: pii: djv036
29 Mavaddat N, Michailidou K, Dennis J. et al. Polygenic Risk Scores for Prediction of Breast Cancer and Breast Cancer Subtypes. Am J Hum Genet 2018;
30 Antoniou AC, Wang X, Fredericksen ZS. et al. 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 2010; 42: 885-892
31 Haberle L, Hein A, Rubner 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
32 Haiman CA, Chen GK, Vachon CM. et al. A common variant at the TERTCLPTM1 L locus is associated with estrogen receptor-negative breast cancer. Nat Genet 2011; 43: 1210-1214
33 Milne RL, Benitez J, Nevanlinna H. et al. Risk of estrogen receptor-positive and ‑negative breast cancer and single-nucleotide polymorphism 2q35-rs13387042. J Natl Cancer Inst 2009; 101: 1012-1018
34 Milne RL, Kuchenbaecker KB, Michailidou K. et al. Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer. Nat Genet 2017; 49: 1767-1778
35 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 2014; 35: 1012-1019
36 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
37 Stevens KN, Vachon CM, Lee AM. et al. Common breast cancer susceptibility loci are associated with triple-negative breast cancer. Cancer Res 2011; 71: 6240-6249
38 Broeks A, Schmidt MK, Sherman ME. et al. Low penetrance breast cancer susceptibility loci are associated with specific breast tumor subtypes: findings from the Breast Cancer Association Consortium. Hum Mol Genet 2011; 20: 3289-3303
39 Figueroa JD, Garcia-Closas M, Humphreys M. et al. Associations of common variants at 1p11.2 and 14q24.1 (RAD51L1) with breast cancer risk and heterogeneity by tumor subtype: findings from the Breast Cancer Association Consortium. Hum Mol Genet 2011; 20: 4693-4706
40 Yang XR, Chang-Claude J, Goode EL. et al. Associations of breast cancer risk factors with tumor subtypes: a pooled analysis from the Breast Cancer Association Consortium studies. J Natl Cancer Inst 2011; 103: 250-263
41 Rudolph A, Song M, Brook MN. et al. Joint associations of a polygenic risk score and environmental risk factors for breast cancer in the Breast Cancer Association Consortium. Int J Epidemiol 2018;
42 Vachon CM, Pankratz VS, Scott CG. et al. The contributions of breast density and common genetic variation to breast cancer risk. J Natl Cancer Inst 2015; 107: pii: dju397
43 Vachon CM, Scott CG, Fasching PA. et al. Common breast cancer susceptibility variants in LSP1 and RAD51L1 are associated with mammographic density measures that predict breast cancer risk. Cancer Epidemiol Biomarkers Prev 2012; 21: 1156-1166
44 Cutress RI, McIntosh SA, Potter S. et al. Opportunities and priorities for breast surgical research. Lancet Oncol 2018; 19: e521-e533
45 Kim HJ, Dominici L, Rosenberg S. et al. Surgical treatment after neoadjuvant systemic therapy in young women with breast cancer: Results from a prospective cohort study. San Antonio Breast Cancer Symposium 2018 Abstr. GS6-01
46 Rosenberg SM, OʼNeill A, Sepucha K. et al. The impact of breast cancer surgery on quality of life: Long term results from E5103. San Antonio Breast Cancer Symposium 2018 Abstr. GS6-05
47 Dominici LS, Hu J, King TA. et al. Local therapy and quality of life outcomes in young women with breast cancer. San Antonio Breast Cancer Symposium 2018 Abstr. GS6-06
48 Bani MR, Beckmann K, Engel J. et al. Correlates of the desire for improved cosmetic results after breast-conserving therapy and mastectomy in breast cancer patients. Breast 2008; 17: 640-645
49 Kuehn T, Bauerfeind I, Fehm T. et al. Sentinel-lymph-node biopsy in patients with breast cancer before and after neoadjuvant chemotherapy (SENTINA): a prospective, multicentre cohort study. Lancet Oncol 2013; 14: 609-618
50 Kolberg HC, Liedtke C, Bauerfeind I. et al. Residual axillary involvement in early breast cancer in patients with positive sentinel nodes after neoadjuvant chemotherapy (NACT). San Antonio Breast Cancer Symposium 2018 Abstr. PD8-02
51 Liedtke C, Kolberg HC, Kerschke L. et al. Systematic analysis of parameters predicting pathological axillary status (ypN0 vs. ypN+) in patients with breast cancer converting from cN+ to ycN0 through primary systemic therapy (PST). Clin Exp Metastasis 2018; 35: 777-783
52 Giuliano AE, Hunt KK, Ballman KV. et al. Axillary dissection vs. no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. JAMA 2011; 305: 569-575
53 Rutgers EJ, Donker M, Poncet C. et al. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer patients: 10 year follow up results of the EORTC AMAROS trial (EORTC10981/22023). San Antonio Breast Cancer Symposium 2018 Abstr. GS4-01
54 Vicini FA, Cecchini RS, White JR. et al. Primary results of NSABP B‑39/RTOG 0413 (NRG Oncology): A randomized phase III study of conventional whole breast irradiation (WBI) versus partial breast irradiation (PBI) for women with stage 0, I, or II breast cancer. San Antonio Breast Cancer Symposium 2018 Abstr. GS4-02
55 Kommission Mamma der Arbeitsgemeinschaft Gynäkologische Onkologie e. V. in der Deutschen Gesellschaft für Gynäkologie und Geburtshilfe e. V. sowie in der Deutschen Krebsgesellschaft e. V. Diagnostik und Therapie von Patientinnen mit primärem und metastasiertem Brustkrebs. Online: 2018 ; Stand: 07.07.2018 https://wwwago-onlinede/fileadmin/downloads/leitlinien/mamma/2017-03/AGO_deutsch/PDF_Gesamtdatei_deutsch/Alle_aktuellen_Empfehlungen_2018pdf
56 Wockel A, Festl J, Stuber 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 2 with Recommendations for the Therapy of Primary, Recurrent and Advanced Breast Cancer. Geburtsh Frauenheilk 2018; 78: 1056-1088
57 Wockel A, Festl J, Stuber 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
58 Dodwell D, Taylor C, McGale P. et al. Regional lymph node irradiation in early stage breast cancer: An EBCTCG meta-analysis of 13000 women in 14 trials. San Antonio Breast Cancer Symposium 2018 Abstr. GS4-02
59 Cortazar P, Geyer jr CE. Pathological complete response in neoadjuvant treatment of breast cancer. Ann Surg Oncol 2015; 22: 1441-1446
60 Fasching PA, Heusinger K, Haeberle L. et al. Ki67, chemotherapy response, and prognosis in breast cancer patients receiving neoadjuvant treatment. BMC Cancer 2011; 11: 486
61 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 Gepar-Quinto Study. J Clin Oncol 2018;
62 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
63 Wunderle M, Gass P, Haberle 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
64 Untch M, Fasching PA, Konecny GE. et al. Pathologic complete response after neoadjuvant chemotherapy plus trastuzumab predicts favorable survival in human epidermal growth factor receptor 2-overexpressing breast cancer: results from the TECHNO trial of the AGO and GBG study groups. J Clin Oncol 2011; 29: 3351-3357
65 Untch M, von Minckwitz G, Konecny GE. et al. PREPARE trial: a randomized phase III trial comparing preoperative, dose-dense, dose-intensified chemotherapy with epirubicin, paclitaxel, and CMF versus a standarddosed epirubicin-cyclophosphamide followed by paclitaxel with or without darbepoetin alfa in primary breast cancer-outcome on prognosis. Ann Oncol 2011; 22: 1999-2006
66 Untch M, Fasching PA, Konecny GE. et al. PREPARE trial: a randomized phase III trial comparing preoperative, dose-dense, dose-intensified chemotherapy with epirubicin, paclitaxel and CMF versus a standard-dosed epirubicin/cyclophosphamide followed by paclitaxel ± darbepoetin alfa in primary breast cancer-results at the time of surgery. Ann Oncol 2011; 22: 1988-1998
67 Masuda N, Lee SJ, Ohtani S. et al. Adjuvant Capecitabine for Breast Cancer after Preoperative Chemotherapy. N Engl J Med 2017; 376: 2147-2159
68 Adams S, Loi S, Toppmeyer DL. et al. KEYNOTE‑086 cohort B: Pembrolizumab monotherapy for PD‑L1-positive, previously untreated, metastatic triple-negative breast cancer (mTNBC) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5–9; San Antonio, TX Philadelphia (PA): AACR. Cancer Res 2018 78. Abstr. PF6-10
69 Martín M, Barrios CH, Torrecillas L. et al. Efficacy results from CIBOMA/2004-01_GEICAM/2003-11 study: A randomized phase III trial assessing adjuvant capecitabine after standard chemotherapy for patients with early triple negative breast cancer. San Antonio Breast Cancer Symposium 2018 Abstr. GS2-04
70 Gass P, Lux MP, Rauh C. et al. Prediction of pathological complete response and prognosis in patients with neoadjuvant treatment for triplenegative breast cancer. BMC Cancer 2018; 18: 1051
71 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
72 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;
73 Wardley AM, Hiller L, Howard HC. et al. tAnGo: a randomised phase III trial of gemcitabine in paclitaxel-containing, epirubicin/cyclophosphamide-based, adjuvant chemotherapy for early breast cancer: a prospective pulmonary, cardiac and hepatic function evaluation. Br J Cancer 2008; 99: 597-603
74 Swain SM, Tang G, Geyer jr CE. et al. Definitive results of a phase III adjuvant trial comparing three chemotherapy regimens in women with operable, node-positive breast cancer: the NSABP B‑38 trial. J Clin Oncol 2013; 31: 3197-3204
75 Earl HM, Vallier AL, Hiller L. et al. Effects of the addition of gemcitabine, and paclitaxel-first sequencing, in neoadjuvant sequential epirubicin, cyclophosphamide, and paclitaxel for women with high-risk early breast cancer (Neo-tAnGo): an open-label, 2×2 factorial randomised phase 3 trial. Lancet Oncol 2014; 15: 201-212
76 Bear HD, Tang G, Rastogi P. et al. Bevacizumab added to neoadjuvant chemotherapy for breast cancer. N Engl J Med 2012; 366: 310-320
77 Bear HD, Tang G, Rastogi P. et al. Neoadjuvant plus adjuvant bevacizumab in early breast cancer (NSABP B‑40 [NRG Oncology]): secondary outcomes of a phase 3, randomised controlled trial. Lancet Oncol 2015; 16: 1037-1048
78 von Minckwitz G, Timms K, Untch M. et al. Homologous repair deficiency (HRD) as measure to predict the effect of carboplatin on survival in the neoadjuvant phase II trial GeparSixto in triple-negative early breast cancer. Cancer Res 2017 77. Abstr. P1-09-02
79 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
80 Untch M, Jackisch C, Schneeweiss A. et al. Nab-paclitaxel versus solventbased paclitaxel in neoadjuvant chemotherapy for early breast cancer (GeparSepto-GBG 69): a randomised, phase 3 trial. Lancet Oncol 2016; 17: 345-356
81 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-cyclosphosphamide for patients with early breast cancer – GBG69 [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5–9; San Antonio, TX Philadelphia (PA): AACR. Cancer Res 2018 78. Abstr. GS3-05
82 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
83 Gluz O, Nitz U, Liedtke C. et al. Impact of 12 weeks nab-paclitaxel + carboplatin or gemcitabine followed by anthracycline administration according to pCR in triple-negative early breast cancer: Survival results of WSG-ADAPT‑TN phase II trial. J Clin Oncol 2018 36. (Suppl): Abstr. 573
84 Gluz O, Nitz U, Liedtke C. et al. No survival benefit of chemotherapy escalation in patients with pCR and high-immune triple-negative early breast cancer in the neoadjuvant WSG-ADAPT‑TN trial. San Antonio Breast Cancer Symposium 2018 ; Abstr. GS5-06
85 Cortazar P, Zhang L, Untch M. et al. Pathological complete response and long-termclinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet 2014; 384: 164-172
86 Sparano JA, Gray RJ, Makower DF. et al. Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer. N Engl J Med 2018; 379: 111-121
87 Wagner LI, Gray RJ, Garcia S. et al. Symptoms and health-related quality of life on endocrine therapy alone (E) versus chemoendocrine therapy (C + E): TAILORx patient-reported outcomes results. San Antonio Breast Cancer Symposium 2018 Abstr. GS6-03
88 Janni W, Schneeweiss A, Müller V. et al. Update Breast Cancer 2019 Part 2 – Implementation of Novel Diagnostics and Therapeutics in Advanced Breast Cancer Patients in Clinical Practice. Geburtsh Frauenheilk 2019; 268-280
89 Early Breast Cancer Trialistsʼ Collaborative Group. Effects of prolonging adjuvant aromatase inhibitor therapy beyond five years on recurrence and cause-specific mortality: An EBCTCG meta-analysis of individual patient data from 12 randomised trials including 24912 women. San Antonio Breast Cancer Symposium 2018 Abstr. GS3-03
90 Ohtani S, Iijima K, Higaki K. et al. A prospective randomized multi-center open-label phase III trial of extending aromatase-inhibitor adjuvant therapy to 10 years – Results from 1697 postmenopausal women in the N‑SAS BC05 trial: Arimidex extended adjuvant randomized study (AERAS). San Antonio Breast Cancer Symposium 2018 Abstr. GS3-04
91 Baselga J, Campone M, Piccart M. et al. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med 2012; 366: 520-529
92 Tesch H, Stoetzer O, Decker T. et al. Efficacy and safety of everolimus plus exemestane in postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer: Results of the single-arm, phase IIIB 4EVER trial. Int J Cancer 2019; 144: 877-885
93 Dowsett M, Jacobs S, Johnston S. et al. PALLET: A neoadjuvant study to compare the clinical and antiproliferative effects of letrozole with and without palbociclib. San Antonio Breast Cancer Symposium 2018 Abstr. GS3-02
94 Hadji P, Blettner M, Harbeck N. et al. The Patientʼs Anastrozole Compliance to Therapy (PACT) Program: a randomized, in-practice study on the impact of a standardized information program on persistence and compliance to adjuvant endocrine therapy in postmenopausal women with early breast cancer. Ann Oncol 2013; 24: 1505-1512
95 Hadji P, Jackisch C, Bolten W. et al. COMPliance and Arthralgia in Clinical Therapy: the COMPACT trial, assessing the incidence of arthralgia, and compliance within the first year of adjuvant anastrozole therapy. Ann Oncol 2014; 25: 372-377
96 Hadji P, Ziller V, Kyvernitakis J. et al. Persistence in patients with breast cancer treated with tamoxifen or aromatase inhibitors: a retrospective database analysis. Breast Cancer Res Treat 2013; 138: 185-191
97 Nabieva N, Fehm T, Haberle L. et al. Influence of side-effects on early therapy persistence with letrozole in post-menopausal patients with early breast cancer: Results of the prospective EvAluate-TM study. Eur J Cancer 2018; 96: 82-90
98 Nabieva N, Kellner S, Fehm T. et al. Influence of patient and tumor characteristics on early therapy persistence with letrozole in postmenopausal women with early breast cancer: results of the prospective Evaluate-TM study with 3941 patients. Ann Oncol 2018; 29: 186-192
99 Fernandez-Gonzalez S, Falo C, Pla MJ. et al. The Shift From Sentinel Lymph Node Biopsy Performed Either Before or After Neoadjuvant Systemic Therapy in the Clinical Negative Nodes of Breast Cancer Patients. Results, and the Advantages and Disadvantages of Both Procedures. Clin Breast Cancer 2018; 18: 71-77
100 Fasching PA, Gass P, Hein A. Neoadjuvant Treatment of Breast Cancer – Advances and Limitations. Breast Care (Basel) 2016; 11: 313-314
101 Robertson JFR, Dowsett M, Bliss JM. et al. Peri-operative Aromatase Inhibitor treatment in determining or predicting Longterm Outcome in Early Breast Cancer – the POETIC* Trial (CRUK/07/015) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5–9; San Antonio, TX Philadelphia (PA): AACR. Cancer Res 2018 78. Abstr. GS1-03
102 Spring LM, Fell G, Arfe A. et al. Pathological complete response after neoadjuvant chemotherapy and impact on breast cancer recurrence and mortality, stratified by breast cancer subtypes and adjuvant chemotherapy usage: Individual patient-level meta-analyses of over 27 000 patients. San Antonio Breast Cancer Symposium 2018 Abstr. GS2-03
103 von Minckwitz G, Huang CS, Mano MS. et al. Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer. N Engl J Med 2018;
104 Geyer jr CE, Huang CS, Mano MS. et al. Phase III study of trastuzumab emtansine (T‑DM1) vs. trastuzumab as adjuvant therapy in patients with HER2-positive early breast cancer with residual invasive disease after neoadjuvant chemotherapy and HER2-targeted therapy including trastuzumab: Primary results from KATHERINE. San Antonio Breast Cancer Symposium 2018 Abstr. GS1-10
105 Fasching PA, Hartkopf AD, Gass P. et al. Efficacy of neoadjuvant pertuzumab in addition to chemotherapy and trastuzumab in routine clinical treatment of patients with primary breast cancer: a multicentric analysis. Breast Cancer Res Treat 2018;
106 Refae S, Pistilli B, Delaloge S. Extended anti-HER2 therapy in early breast cancer: longer beats shorter?. Curr Opin Oncol 2016; 28: 469-475
107 Pivot X, Romieu G, Debled M. et al. PHARE randomized trial final results comparing 6 to 12 months of trastuzumab in adjuvant early breast cancer. San Antonio Breast Cancer Symposium 2018 Abstr. GS2-07