Download PDF
CC BY-NC-ND 4.0 · Geburtshilfe Frauenheilkd 2018; 78(11): 1110-1118
DOI: 10.1055/a-0715-2821
GebFra Science
Review/Übersicht
Georg Thieme Verlag KG Stuttgart · New York

Update Mammakarzinom 2018 (Teil 3) – Genomforschung, individualisierte Medizin und Immuntherapien – mitten in einer neuen Ära: Prävention und Therapie des frühen Mammakarzinoms

Article in several languages: English | deutsch
Achim Wöckel
1   Department of Gynecology and Obstetrics, University Hospital Würzburg, Germany
,
Michael P. Lux
2   Erlangen University Hospital, Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany
,
Wolfgang Janni
3   Department of Gynecology and Obstetrics, Ulm University Hospital, Ulm, Germany
,
Andreas D. Hartkopf
4   Department of Obstetrics and Gynecology, University of Tübingen, Tübingen, Germany
,
Naiba Nabieva
2   Erlangen University Hospital, Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany
,
Florin-Andrei Taran
4   Department of Obstetrics and Gynecology, University of Tübingen, Tübingen, Germany
,
Friedrich Overkamp
5   OncoConsult Hamburg GmbH, Hamburg, Germany
,
Peyman Hadji
6   Department of Bone Oncology, Nordwest Hospital, Frankfurt, Germany
,
Hans Tesch
7   Oncology Practice at Bethanien Hospital Frankfurt, Frankfurt, Germany
,
Johannes Ettl
8   Department of Obstetrics and Gynecology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
,
Diana Lüftner
9   Charité University Hospital, Berlin, Campus Benjamin Franklin, Department of Hematology, Oncology and Tumour Immunology, Berlin, Germany
,
Volkmar Müller
10   Department of Gynecology, Hamburg-Eppendorf University Medical Center, Hamburg, Germany
,
Manfred Welslau
11   Onkologie Aschaffenburg, Hämatolo-Onkologische Schwerpunktpraxis am Klinikum Aschaffenburg, Aschaffenburg, Germany
,
Erik Belleville
12   ClinSol GmbH & Co KG, Würzburg, Germany
,
Sara Y. Brucker
4   Department of Obstetrics and Gynecology, University of Tübingen, Tübingen, Germany
,
Florian Schütz
13   Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany
,
Peter A. Fasching
2   Erlangen University Hospital, Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany
,
Tanja N. Fehm
14   Department of Gynecology and Obstetrics, University Hospital Düsseldorf, Düsseldorf, Germany
,
Andreas Schneeweiss
13   Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany
15   National Center for Tumor Diseases, Division Gynecologic Oncology, University Hospital Heidelberg, Heidelberg, Germany
,
Hans-Christian Kolberg
16   Department of Gynecology and Obstetrics, Marienhospital Bottrop, Bottrop, Germany
› Author Affiliations
Further Information

Publication History

received 09 August 2018

accepted 23 August 2018

Publication Date:
26 November 2018 (online)

Also available at
   Permissions and Reprints

Zusammenfassung

Beim primären, frühen Mammakarzinom zielt die Behandlungsplanung auf ein immer besseres Verständnis der Erkrankung ab. Die Identifikation von Patientinnen mit einer exzellenten Prognose könnte dieser Gruppe helfen, unnötige Therapien zu vermeiden. Weiterhin wird die Planung der Therapie immer weiter auf die Patientin abgestimmt. Das Wissen über Patientinnen, die besonders von einer Chemotherapie profitieren, wächst genauso wie das Wissen um Patientinnen, die von einer Immuntherapie profitieren könnten. Hinsichtlich der Immuntherapien stehen die durchgeführten Studien kurz vor der Publikation. Einzelne kleinere Studien bieten einen ersten Einblick in die Wirksamkeit der Checkpoint-Inhibitoren (Anti-PD1/PDL1-Therapien). Nicht zuletzt konnte kürzlich eine der größten Brustkrebsstudien aller Zeiten zu Ende geführt werden. Die Anwendung eines Multigentests konnte zeigen, dass er ausreicht, um Patientinnen mit einer so guten Prognose zu identifizieren, dass keine Chemotherapie nötig ist. Dieser Review-Artikel soll die aktuellen Studien zusammenfassen und einen Ausblick der gegenwärtigen Entwicklungen geben.

Schlüsselwörter

Mammakarzinom - Behandlung - Metastasen - CDK4/6, PD1/PDL1, Studien - Risiko - Prävention
 

  • References/Literatur

  • 1 Taran FA, Schneeweiss A, Lux MP. et al. Update Breast Cancer 2018 (Part 1) – Primary Breast Cancer and Biomarkers. Geburtsh Frauenheilk 2018; 78: 237-245
    Article in Thieme ConnectPubMedGoogle Scholar
  • 2 Schneeweiss A, Lux MP, Janni W. et al. Update Breast Cancer 2018 (Part 2) – Advanced Breast Cancer, Quality of Life and Prevention. Geburtsh Frauenheilk 2018; 78: 246-259
    Article in Thieme ConnectPubMedGoogle Scholar
  • 3 Untch M, Wurstlein R, Marschner N. et al. 4th International Consensus Conference on Advanced Breast Cancer (ABC4), Lisbon, November 4, 2017: ABC4 Consensus: Assessment by a Panel of German Experts. Geburtsh Frauenheilk 2018; 78: 469-480
    Article in Thieme ConnectPubMedGoogle Scholar
  • 4 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
    CrossrefPubMedGoogle Scholar
  • 5 Michailidou K, Beesley J, Lindstrom S. et al. Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer. Nat Genet 2015; 47: 373-380
    CrossrefPubMedGoogle Scholar
  • 6 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: 353-361 361.e1–361.e2
    CrossrefPubMedGoogle Scholar
  • 7 Michailidou K, Lindstrom S, Dennis J. et al. Association analysis identifies 65 new breast cancer risk loci. Nature 2017; 551: 92-94
    PubMedGoogle Scholar
  • 8 Ahmed S, Thomas G, Ghoussaini M. et al. Newly discovered breast cancer susceptibility loci on 3p24 and 17q23.2. Nat Genet 2009; 41: 585-590
    CrossrefPubMedGoogle Scholar
  • 9 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
    CrossrefPubMedGoogle Scholar
  • 10 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
    CrossrefPubMedGoogle Scholar
  • 11 Cox A, Dunning AM, Garcia-Closas M. et al. A common coding variant in CASP8 is associated with breast cancer risk. Nat Genet 2007; 39: 352-358
    CrossrefPubMedGoogle Scholar
  • 12 Easton DF, Pooley KA, Dunning AM. et al. Genome-wide association study identifies novel breast cancer susceptibility loci. Nature 2007; 447: 1087-1093
    PubMedGoogle Scholar
  • 13 Fasching PA, Ekici AB, Adamietz BR. et al. Breast Cancer Risk – Genes, Environment and Clinics. Geburtsh Frauenheilk 2011; 71: 1056-1066
    Article in Thieme ConnectPubMedGoogle Scholar
  • 14 Fasching PA, Ekici AB, Wachter DL. et al. Breast Cancer Risk – From Genetics to Molecular Understanding of Pathogenesis. Geburtsh Frauenheilk 2013; 73: 1228-1235
    Article in Thieme ConnectPubMedGoogle Scholar
  • 15 Fletcher O, Johnson N, Orr N. et al. Novel breast cancer susceptibility locus at 9q31.2: results of a genome-wide association study. J Natl Cancer Inst 2011; 103: 425-435
    CrossrefPubMedGoogle Scholar
  • 16 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
    CrossrefPubMedGoogle Scholar
  • 17 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
    CrossrefPubMedGoogle Scholar
  • 18 Haiman CA, Chen GK, Vachon CM. et al. A common variant at the TERT-CLPTM1 L locus is associated with estrogen receptor-negative breast cancer. Nat Genet 2011; 43: 1210-1214
    CrossrefPubMedGoogle Scholar
  • 19 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
    CrossrefPubMedGoogle Scholar
  • 20 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
    CrossrefPubMedGoogle Scholar
  • 21 Siddiq A, Couch FJ, Chen GK. et al. A meta-analysis of genome-wide association studies of breast cancer identifies two novel susceptibility loci at 6q14 and 20q11. Hum Mol Genet 2012; 21: 5373-5384
    CrossrefPubMedGoogle Scholar
  • 22 Stacey SN, Manolescu A, Sulem P. et al. Common variants on chromosomes 2q35 and 16q12 confer susceptibility to estrogen receptor-positive breast cancer. Nat Genet 2007; 39: 865-869
    CrossrefPubMedGoogle Scholar
  • 23 Stacey SN, Manolescu A, Sulem P. et al. Common variants on chromosome 5p12 confer susceptibility to estrogen receptor-positive breast cancer. Nat Genet 2008; 40: 703-706
    CrossrefPubMedGoogle Scholar
  • 24 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
    CrossrefPubMedGoogle Scholar
  • 25 Thomas G, Jacobs KB, Kraft P. et al. A multistage genome-wide association study in breast cancer identifies two new risk alleles at 1p11.2 and 14q24.1 (RAD51L1). Nat Genet 2009; 41: 579-584
    CrossrefPubMedGoogle Scholar
  • 26 Turnbull C, Ahmed S, Morrison J. et al. Genome-wide association study identifies five new breast cancer susceptibility loci. Nat Genet 2010; 42: 504-507
    CrossrefPubMedGoogle Scholar
  • 27 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
    Article in Thieme ConnectPubMedGoogle Scholar
  • 28 Zheng W, Long J, Gao YT. et al. Genome-wide association study identifies a new breast cancer susceptibility locus at 6q25.1. Nat Genet 2009; 41: 324-328
    CrossrefPubMedGoogle Scholar
  • 29 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
    CrossrefPubMedGoogle Scholar
  • 30 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
    CrossrefPubMedGoogle Scholar
  • 31 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
    CrossrefPubMedGoogle Scholar
  • 32 Garcia-Closas M, Gunsoy NB, Chatterjee N. Combined associations of genetic and environmental risk factors: implications for prevention of breast cancer. J Natl Cancer Inst 2014; 106: pii:dju305 doi:10.1093/jnci/dju305
    CrossrefPubMedGoogle Scholar
  • 33 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 doi:10.1093/jnci/djv036
    CrossrefPubMedGoogle Scholar
  • 34 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 doi:10.1093/jnci/dju397
    CrossrefPubMedGoogle Scholar
  • 35 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; DOI: 10.1093/ije/dyx242.
    CrossrefPubMedGoogle Scholar
  • 36 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
    Article in Thieme ConnectPubMedGoogle Scholar
  • 37 Simard J, Chiarelli AM. Personalized risk assessment for prevention and early detection of breast cancer: Integration and Implementation. 2018 Online: https://www.genomecanada.ca/sites/default/files/2017lsarp_backgrounder_en.pdf last access: 01.04.2018
    PubMedGoogle Scholar
  • 38 Unicancer. Randomized, Comparison Of Risk-Stratified versus Standard Breast Cancer Screening In European Women Aged 40–74. 2017 Online: https://cordis.europa.eu/project/rcn/212694_en.html last access: 01.04.2018
    PubMedGoogle Scholar
  • 39 Shieh Y, Eklund M, Madlensky L. et al. Breast Cancer Screening in the Precision Medicine Era: Risk-Based Screening in a Population-Based Trial. J Natl Cancer Inst 2017; DOI: 10.1093/jnci/djw290.
    CrossrefPubMedGoogle Scholar
  • 40 Evans DG, Astley S, Stavrinos P. et al. Improvement in risk prediction, early detection and prevention of breast cancer in the NHS Breast Screening Programme and family history clinics: a dual cohort study. Southampton (UK): NIHR Journals Library; 2016
    Google Scholar
  • 41 ASSURE Consortium. Final Report Summary – ASSURE (Adapting Breast Cancer Screening Strategy Using Personalised RiskEstimation). 2016 Online: https://cordis.europa.eu/result/rcn/187468_en.html last access: 01.04.2018
    PubMedGoogle Scholar
  • 42 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
    PubMedGoogle Scholar
  • 43 Couch FJ, Shimelis H, Hu C. et al. Associations Between Cancer Predisposition Testing Panel Genes and Breast Cancer. JAMA Oncol 2017; 3: 1190-1196
    CrossrefPubMedGoogle Scholar
  • 44 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; DOI: 10.1200/JCO.2017.77.2285.
    CrossrefPubMedGoogle Scholar
  • 45 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
    CrossrefPubMedGoogle Scholar
  • 46 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; 78: Abstr.. PD1-02
    PubMedGoogle Scholar
  • 47 Nolan E, Vaillant F, Branstetter D. et al. RANK ligand as a potential target for breast cancer prevention in BRCA1-mutation carriers. Nat Med 2016; 22: 933-939
    CrossrefPubMedGoogle Scholar
  • 48 Sigl V, Jones LP, Penninger JM. RANKL/RANK: from bone loss to the prevention of breast cancer. Open Biol 2016; 6: pii:160230
    CrossrefPubMedGoogle Scholar
  • 49 Sigl V, Owusu-Boaitey K, Joshi PA. et al. RANKL/RANK control Brca1 mutation-driven mammary tumors. Cell Res 2016; 26: 761-774
    CrossrefPubMedGoogle Scholar
  • 50 Bayer CM, Beckmann MW, Fasching PA. Updates on the role of receptor activator of nuclear factor kappaB/receptor activator of nuclear factor kappaB ligand/osteoprotegerin pathway in breast cancer risk and treatment. Curr Opin Obstet Gynecol 2017; 29: 4-11
    CrossrefPubMedGoogle Scholar
  • 51 Francis P, Singer C, Saunders C. et al. BRCA-P: An international randomised phase III study evaluating the RANK ligand inhibitor denosumab for the prevention of breast cancer in BRCA1 mutation carriers [2018–2022]. Online: http://purlorg/au-research/grants/nhmrc/1140715 and https://researchdata.ands.org.au/brca-p-an-mutation-carriers/1319302 last access: 02.04.2018
    PubMedGoogle Scholar
  • 52 Kuchenbaecker KB, Hopper JL, Barnes DR. et al. Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers. JAMA 2017; 317: 2402-2416
    CrossrefPubMedGoogle Scholar
  • 53 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; DOI: 10.1016/S1470-2045(17)30891-4.
    CrossrefPubMedGoogle Scholar
  • 54 Fasching PA. Breast cancer in young women: do BRCA1 or BRCA2 mutations matter?. Lancet Oncol 2018; DOI: 10.1016/S1470-2045(18)30008-1.
    CrossrefPubMedGoogle Scholar
  • 55 Evron E, Ben David MA, Goldberg H. et al. Phase II national clinical trial of prophylactic irradiation to the contralateral breast for BRCA mutation carriers treated for early breast cancer (EBC). J Clin Oncol 2018; 36 (Suppl.) Abstr.. 514
    PubMedGoogle Scholar
  • 56 Poortmans PM, Collette S, Kirkove C. et al. Internal Mammary and Medial Supraclavicular Irradiation in Breast Cancer. N Engl J Med 2015; 373: 317-327
    CrossrefPubMedGoogle Scholar
  • 57 Poortmans P, Collette S, Struikmans H. et al. Fifteen-year results of the randomised EORTC trial 22922/10925 investigating internal mammary and medial supraclavicular (IM-MS) lymph node irradiation in stage I–III breast cancer. J Clin Oncol 2018; 36 (Suppl.) Abstr.. 504
    PubMedGoogle Scholar
  • 58 Herrera FG, Bourhis J, Coukos G. Radiotherapy combination opportunities leveraging immunity for the next oncology practice. CA Cancer J Clin 2017; 67: 65-85
    CrossrefPubMedGoogle Scholar
  • 59 McArthur HL, Barker CA, Gucalp A. et al. A phase II, single arm study assessing the efficacy of pembrolizumab (Pembro) plus radiotherapy (RT) in metastatic triple negative breast cancer (mTNBC). J Clin Oncol 2018; 36 (Suppl.) Abstr.. 1017
    CrossrefPubMedGoogle Scholar
  • 60 Formenti SC, Golden EB, Goldberg JD. et al. Results of a phase I–II study of adjuvant concurrent carboplatin and accelerated radiotherapy for triple negative breast cancer. Oncoimmunology 2017; 6: e1274479
    CrossrefPubMedGoogle Scholar
  • 61 Ngwa W, Irabor OC, Schoenfeld JD. et al. Using immunotherapy to boost the abscopal effect. Nat Rev Cancer 2018; 18: 313-322
    CrossrefPubMedGoogle Scholar
  • 62 Davies C, Godwin J, Gray R. et al. Early Breast Cancer Trialistsʼ Collaborative Group. Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet 2011; 378: 771-784
    CrossrefPubMedGoogle Scholar
  • 63 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
    CrossrefPubMedGoogle Scholar
  • 64 Pagani O, Regan MM, Walley BA. et al. Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. N Engl J Med 2014; 371: 107-118
    CrossrefPubMedGoogle Scholar
  • 65 Francis PA, Regan MM, Fleming GF. et al. Adjuvant ovarian suppression in premenopausal breast cancer. N Engl J Med 2015; 372: 436-446
    CrossrefPubMedGoogle Scholar
  • 66 Francis PA, Pagani O, Fleming GF. et al. Tailoring Adjuvant Endocrine Therapy for Premenopausal Breast Cancer. N Engl J Med 2018; 379: 122-137
    CrossrefPubMedGoogle Scholar
  • 67 Regan MM, Francis PA, Pagani O. et al. Absolute improvements in freedom from distant recurrence with adjuvant endocrine therapies for premenopausal women with hormone receptor-positive (HR+) HER2-negative breast cancer (BC): Results from TEXT and SOFT. J Clin Oncol 2018; 36 (Suppl.) Abstr.. 503
    CrossrefPubMedGoogle Scholar
  • 68 Noh WC, Lee JW, Nam SJ. et al. Role of adding ovarian function suppression to tamoxifen in young women with hormone-sensitive breast cancer who remain premenopausal or resume menstruation after chemotherapy: The ASTRRA study. J Clin Oncol 2018; 36 (Suppl.) Abstr. 502
    PubMedGoogle Scholar
  • 69 Leitlinienprogramm Onkologie (Deutsche Krebsgesellschaft und Deutsche Krebshilfe und AWMF). S3-Leitlinie Früherkennung, Diagnose, Therapie und Nachsorge des Mammakarzinoms, Version 4.0, 2017 AWMF Registernummer: 032-045OL. 2017 Online: http://www.leitlinienprogramm-onkologie.de/leitlinien/mammakarzinom/ last access: 23.07.2018
    PubMedGoogle Scholar
  • 70 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
    CrossrefPubMedGoogle Scholar
  • 71 Gnant M, Pfeiler G, Dubsky PC. et al. The impact of adjuvant denosumab on disease-free survival: Results from 3,425 postmenopausal patients of the ABCSG-18 trial. Cancer Res 2016; 76 (Suppl. 04) Abstract. S2-02
    PubMedGoogle Scholar
  • 72 Coleman RE, Finkelstein D, Barrios CH. et al. Adjuvant denosumab in early breast cancer: First results from the international multicenter randomized phase III placebo controlled D-CARE study. J Clin Oncol 2018; 36 (Suppl.) Abstr.. 501
    PubMedGoogle Scholar
  • 73 Gnant M, Pfeiler G, Steger GG. et al. Adjuvant denosumab in early breast cancer: Disease-free survival analysis of 3,425 postmenopausal patients in the ABCSG-18 trial. J Clin Oncol 2018; 36 (Suppl.) Abstr.. 500
    PubMedGoogle Scholar
  • 74 Early Breast Cancer Trialistsʼ Collaborative Group. Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials. Lancet Oncol 2018; 19: 27-39
    CrossrefPubMedGoogle Scholar
  • 75 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
    CrossrefPubMedGoogle Scholar
  • 76 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
    CrossrefPubMedGoogle Scholar
  • 77 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
    CrossrefPubMedGoogle Scholar
  • 78 Gianni L, Pienkowski T, Im YH. et al. 5-year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer (NeoSphere): a multicentre, open-label, phase 2 randomised trial. Lancet Oncol 2016; 17: 791-800
    CrossrefPubMedGoogle Scholar
  • 79 Guarneri V, Dieci MV, Bisagni G. et al. De-escalated treatment with trastuzumab-pertuzumab-letrozole in patients with HR+/HER2+ operable breast cancer with Ki67 response after 2 weeks letrozole: Final results of the PerELISA neoadjuvant study. J Clin Oncol 2018; 36 (Suppl.) Abstr.. 507
    PubMedGoogle Scholar
  • 80 Prat A, De Angelis C, Pascual T. et al. HER2-enriched subtype and ERBB2 mRNA as predictors of pathological complete response following trastuzumab and lapatinib without chemotherapy in early-stage HER2-positive breast cancer: A combined analysis of TBCRC006/023 and PAMELA trials. J Clin Oncol 2018; 36 (Suppl.) Abstr.. 509
    PubMedGoogle Scholar
  • 81 von Minckwitz G, Procter M, de Azambuja E. et al. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer. N Engl J Med 2017; 377: 122-131
    CrossrefPubMedGoogle Scholar
  • 82 Tolaney SM, Barry WT, Dang CT. et al. Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer. N Engl J Med 2015; 372: 134-141
    CrossrefPubMedGoogle Scholar
  • 83 Tolaney SM, Barry WT, Guo H. et al. Seven-year (yr) follow-up of adjuvant paclitaxel (T) and trastuzumab (H) (APT trial) for node-negative, HER2-positive breast cancer (BC). J Clin Oncol 2017; 35: 511
    PubMedGoogle Scholar
  • 84 Sawaki M, Saito T, Baba S. et al. Evaluation of trastuzumab without chemotherapy as a postoperative adjuvant therapy in HER2-positive elderly breast cancer patients: Randomized controlled trial (RESPECT). J Clin Oncol 2018; 36 (Suppl.) Abstr.. 510
    PubMedGoogle Scholar
  • 85 Cameron D, Piccart-Gebhart MJ, Gelber RD. et al. 11 yearsʼ follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial. Lancet 2017; 389: 1195-1205
    CrossrefPubMedGoogle Scholar
  • 86 Pivot X, Romieu G, Debled M. et al. 6 months versus 12 months of adjuvant trastuzumab for patients with HER2-positive early breast cancer (PHARE): a randomised phase 3 trial. Lancet Oncol 2013; 14: 741-748
    CrossrefPubMedGoogle Scholar
  • 87 Joensuu H, Fraser J, Wildiers H. et al. Effect of Adjuvant Trastuzumab for a Duration of 9 Weeks vs. 1 Year With Concomitant Chemotherapy for Early Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: The SOLD Randomized Clinical Trial. JAMA Oncol 2018; DOI: 10.1001/jamaoncol.2018.1380.
    CrossrefPubMedGoogle Scholar
  • 88 Earl HM, Hiller L, Vallier AL. et al. PERSEPHONE: 6 versus 12 months (m) of adjuvant trastuzumab in patients (pts) with HER2 positive (+) early breast cancer (EBC): Randomised phase 3 non-inferiority trial with definitive 4-year (yr) disease-free survival (DFS) results. J Clin Oncol 2018; 36 (Suppl.) Abstr.. 506
    PubMedGoogle Scholar
  • 89 Ravdin PM, Siminoff LA, Davis GJ. et al. Computer program to assist in making decisions about adjuvant therapy for women with early breast cancer. J Clin Oncol 2001; 19: 980-991
    CrossrefPubMedGoogle Scholar
  • 90 Wishart GC, Bajdik CD, Dicks E. et al. PREDICT Plus: development and validation of a prognostic model for early breast cancer that includes HER2. Br J Cancer 2012; 107: 800-807
    CrossrefPubMedGoogle Scholar
  • 91 Cardoso F, vanʼt Veer LJ, Bogaerts J. et al. 70-Gene Signature as an Aid to Treatment Decisions in Early-Stage Breast Cancer. N Engl J Med 2016; 375: 717-729
    CrossrefPubMedGoogle Scholar
  • 92 Paik S, Shak S, Tang G. et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med 2004; 351: 2817-2826
    CrossrefPubMedGoogle Scholar
  • 93 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
    CrossrefPubMedGoogle Scholar
  • 94 Sparano JA, Gray RJ, Makower DF. et al. Prospective Validation of a 21-Gene Expression Assay in Breast Cancer. N Engl J Med 2015; 373: 2005-2014
    CrossrefPubMedGoogle Scholar
  • 95 Cuzick J, Dowsett M, Pineda S. et al. Prognostic value of a combined estrogen receptor, progesterone receptor, Ki-67, and human epidermal growth factor receptor 2 immunohistochemical score and comparison with the Genomic Health recurrence score in early breast cancer. J Clin Oncol 2011; 29: 4273-4278
    CrossrefPubMedGoogle Scholar
  • 96 Dowsett M, Sestak I, Lopez-Knowles E. et al. Comparison of PAM50 risk of recurrence score with oncotype DX and IHC4 for predicting risk of distant recurrence after endocrine therapy. J Clin Oncol 2013; 31: 2783-2790
    CrossrefPubMedGoogle Scholar
  • 97 Filipits M, Rudas M, Jakesz R. et al. A new molecular predictor of distant recurrence in ER-positive, HER2-negative breast cancer adds independent information to conventional clinical risk factors. Clin Cancer Res 2011; 17: 6012-6020
    CrossrefPubMedGoogle Scholar
  • 98 Schmidt M, Fasching PA, Beckmann MW. et al. Biomarkers in Breast Cancer – An Update. Geburtsh Frauenheilk 2012; 72: 819-832
    Article in Thieme ConnectPubMedGoogle Scholar