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Frauenheilkunde up2date 2020; 14(01): 27-42
DOI: 10.1055/a-0854-7203
Gynäkologische Onkologie
Georg Thieme Verlag KG Stuttgart · New York

Adjuvante endokrine Therapie beim primären Mammakarzinom

Natalia Krawczyk
,
Tanja Fehm
,
Eugen Ruckhäberle
Further Information

Publication History

Publication Date:
30 January 2020 (online)

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Endokrine Therapie stellt einen integralen Bestandteil der Mammakarzinomtherapie dar. Bis zu 70% aller Mammakarzinome sind Hormonrezeptor-(HR-)positiv und können endokrin (mit)behandelt werden. Bei erhöhtem Rückfallrisiko wird die Therapie heutzutage tendenziell verlängert und/oder in der Prämenopause durch den Einsatz von GnRH-Analoga intensiviert – wie die aktuellen Empfehlungen zur endokrinen Therapie des primären Mammakarzinoms zeigen.
Kernaussagen

  • Eine endokrine Therapie über 5 Jahre (initiale adjuvante Therapie; IAT) stellt den aktuellen Behandlungsstandard des HR-positiven Mammakarzinoms dar.

  • In der Prämenopause wird in den meisten Fällen die Behandlung mit Tamoxifen über 5 Jahre empfohlen, die bei Hochrisikokonstellation mit paralleler Gabe von GnRH-Analoga ebenfalls über 5 Jahre intensiviert werden kann.

  • Eine IAT bei postmenopausaler Patientin soll neben Tamoxifen standardmäßig einen AI über 2 – 3 Jahre beinhalten (Sequenz-Therapie), während bei erhöhtem Rückfallrisiko und bei lobulärem Karzinom AI-Behandlung über 5 Jahre bevorzugt wird (Upfront-Therapie).

  • Bei hohem Rückfallrisiko kann nach Risiko-Nutzen-Abwägung die endokrine Therapie über 5 Jahre hinaus verlängert werden (erweiterte adjuvante Therapie, EAT): bei prämenopausaler Patientin um weitere 5 Jahre Tamoxifen, in der Postmenopause um 2 – 5 Jahre Aromatasehemmer.

  • In Falle einer EAT nach bereits im Rahmen der IAT erfolgten AI-Gabe ist eine 7- bzw. 7,5-jährige Behandlung mit Aromatasehemmer der 10-jährigen nicht unterlegen.

  • Im Falle einer EAT muss die Patientin über die Zunahme der Nebenwirkungen aufgeklärt werden: 10 vs. 5 Jahre Tamoxifen-Therapie verdoppeln die Rate der Endometriumkarzinome; verlängerte AI-Einnahme ist mit signifikant höheren Osteoporoseraten sowie deutlich erhöhten Frakturraten verbunden.

Schlüsselwörter

endokrine Therapie - primäres Mammakarzinom - Therapieempfehlungen
 

  • Literatur

  • 1 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
    Article in Thieme ConnectPubMedGoogle Scholar
  • 2 AGO Breast Committee. Diagnosis and Treatment of Patients with Primary and Metastatic Breast Cancer. Recommendations 2019 Im Internet: http://www.ago-online.de Stand: 18.03.2019
    PubMedGoogle Scholar
  • 3 Morigi C. Highlights from the 15th St Gallen International Breast Cancer Conference 15–18 March, 2017, Vienna: tailored treatments for patients with early breast cancer. Ecancermedicalscience 2017; 11: 732
    PubMedGoogle Scholar
  • 4 Pan H, Gray R, Braybrooke J. et al. 20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years. N Engl J Med 2017; 377: 1836-1846
    CrossrefPubMedGoogle Scholar
  • 5 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
  • 6 Gluz O, Nitz UA, Christgen M. et al. West German Study Group Phase III PlanB Trial: First Prospective Outcome Data for the 21-Gene Recurrence Score Assay and Concordance of Prognostic Markers by Central and Local Pathology Assessment. J Clin Oncol 2016; 34: 2341-2349
    CrossrefPubMedGoogle Scholar
  • 7 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
  • 8 Bundesministerium für Gesundheit. Bekanntmachung eines Beschlusses des Gemeinsamen Bundesausschusses über eine Änderung der Richtlinie Methoden vertragsärztliche Versorgung: Biomarkerbasierte Tests zur Entscheidung für oder gegen eine adjuvante systemische Chemotherapie beim primären Mammakarzinom vom: 20.06.2019. Bundesanzeiger AT 22.08.2019 B5. Im Internet: https://www.g-ba.de/beschluesse/3809/ Stand: 24.11.2019
    PubMedGoogle Scholar
  • 9 Early Breast Cancer Trialistsʼ Collaborative Group. Davies C, Godwin J, Gray R. et al. 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
  • 10 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
  • 11 Chlebowski RT, Pan K, Col NF. Ovarian suppression in combination endocrine adjuvant therapy in premenopausal women with early breast cancer. Breast Cancer Res Treatment 2017; 161: 185-190
    CrossrefPubMedGoogle Scholar
  • 12 Bellet M, Gray KP, Francis PA. et al. Twelve-Month Estrogen Levels in Premenopausal Women With Hormone Receptor-Positive Breast Cancer Receiving Adjuvant Triptorelin Plus Exemestane or Tamoxifen in the Suppression of Ovarian Function Trial (SOFT): The SOFT-EST Substudy. J Clin Oncol 2016; 34: 1584-1593
    CrossrefPubMedGoogle Scholar
  • 13 Hackshaw A, Baum M, Fornander T. et al. Long-term effectiveness of adjuvant goserelin in premenopausal women with early breast cancer. J Natl Cancer Inst 2009; 101: 341-349
    CrossrefPubMedGoogle Scholar
  • 14 Davies C, Pan H, Godwin J. et al. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet 2013; 381: 805-816
    CrossrefPubMedGoogle Scholar
  • 15 Gray RG, Rea D, Handley K. et al. aTTom: Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years in 6,953 women with early breast cancer. J Clin Oncol 2013; 31 (Suppl. 05) 5-5
    Google Scholar
  • 16 Goss PE. Letrozole in the extended adjuvant setting: MA.17. Breast Cancer Res Treatment 2007; 105 (Suppl. 01) 45-53
    PubMedGoogle Scholar
  • 17 Jakesz R, Greil R, Gnant M. et al. Extended adjuvant therapy with anastrozole among postmenopausal breast cancer patients: results from the randomized Austrian Breast and Colorectal Cancer Study Group Trial 6a. J Natl Cancer Inst 2007; 99: 1845-1853
    CrossrefPubMedGoogle Scholar
  • 18 Mamounas EP, Jeong JH, Wickerham DL. et al. Benefit from exemestane as extended adjuvant therapy after 5 years of adjuvant tamoxifen: intention-to-treat analysis of the National Surgical Adjuvant Breast And Bowel Project B-33 trial. J Clin Oncol 2008; 26: 1965-1971
    CrossrefPubMedGoogle Scholar
  • 19 Ryden L, Heibert Arnlind M, Vitols S. et al. Aromatase inhibitors alone or sequentially combined with tamoxifen in postmenopausal early breast cancer compared with tamoxifen or placebo – Meta-analyses on efficacy and adverse events based on randomized clinical trials. Breast 2016; 26: 106-114
    CrossrefPubMedGoogle Scholar
  • 20 Regan MM, Neven P, Giobbie-Hurder A. et al. Assessment of letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer: the BIG 1-98 randomised clinical trial at 8.1 years median follow-up. Lancet Oncol 2011; 12: 1101-1108
    CrossrefPubMedGoogle Scholar
  • 21 Cuzick J, Sestak I, Baum M. et al. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 10-year analysis of the ATAC trial. Lancet Oncol 2010; 11: 1135-1141
    CrossrefPubMedGoogle Scholar
  • 22 Early Breast Cancer Trialistsʼ Collaborative Group (EBCTCG). Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials. Lancet 2015; 386: 1341-1352
    CrossrefPubMedGoogle Scholar
  • 23 van de Velde CJ, Rea D, Seynaeve C. et al. Adjuvant tamoxifen and exemestane in early breast cancer (TEAM): a randomised phase 3 trial. Lancet 2011; 377: 321-331
    CrossrefPubMedGoogle Scholar
  • 24 Strasser-Weippl K, Sudan G, Ramjeesingh R. et al. Outcomes in women with invasive ductal or invasive lobular early stage breast cancer treated with anastrozole or exemestane in CCTG (NCIC CTG) MA.27. Eur J Cancer 2018; 90: 19-25
    CrossrefPubMedGoogle Scholar
  • 25 Gray R. (EBCTCG) Extended aromatase inhibitor treatment following 5 or more years of endocrine therapy: a metaanalysis of 22192 women in 11 randomised trials. SABCS 2018; GS3-03.
    Google Scholar
  • 26 Goss PE, Ingle JN, Pritchard KI. et al. Extending Aromatase-Inhibitor Adjuvant Therapy to 10 Years. N Engl J Med 2016; 375: 209-219
    CrossrefPubMedGoogle Scholar
  • 27 Zdenkowski N, Forbes JF, Boyle FM. et al. Observation versus late reintroduction of letrozole as adjuvant endocrine therapy for hormone receptor-positive breast cancer (ANZ0501 LATER): an open-label randomised, controlled trial. Ann Oncol/ESMO 2016; 27: 806-812
    Google Scholar
  • 28 Ohtani S, Iijima K, Higaki K. et al. A prospective randomized multicenter open-label phase 3 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). Oral presentation at: 2018 San Antonio Breast Cancer Symposium; December 4 – 8, 2018. San Antonio, TX; Abstr. GS3-04.
    Google Scholar
  • 29 Tjan-Heijnen VCG, van Hellemond IEG, Peer PGM. et al. Extended adjuvant aromatase inhibition after sequential endocrine therapy (DATA): a randomised, phase 3 trial. Lancet Oncol 2017; 18: 1502-1511
    CrossrefPubMedGoogle Scholar
  • 30 Mamounas EP, Bandos H, Lembersky BC. et al. Use of letrozole after aromatase inhibitor-based therapy in postmenopausal breast cancer (NRG Oncology/NSABP B-42): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 2019; 20: 88-99
    CrossrefPubMedGoogle Scholar
  • 31 Gnant M, Steger G, Greil R. et al. A prospective randomized multi-center phase-III trial of additional 2 versus additional 5 years of anastrozole after initial 5 years of adjuvant endocrine therapy – results from 3,484 postmenopausal women in the ABCSG-16 trial. 2017 San Antonio Breast Cancer Symposium. San Antonio, TX; Abstr. GS3-01.
    Google Scholar
  • 32 Colleoni M, Luo W, Karlsson P. et al. Extended adjuvant intermittent letrozole versus continuous letrozole in postmenopausal women with breast cancer (SOLE): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol 2018; 19: 127-138
    CrossrefPubMedGoogle Scholar
  • 33 Blok EJ, Kroep JR, Meershoek-Klein Kranenbarg E. et al. Relevant factors for the optimal duration of extended endocrine therapy in early breast cancer. Breast Cancer Res Treatment 2018; 168: 413-420
    CrossrefPubMedGoogle Scholar
  • 34 Del Mastro L, Mansutti M, Bisagni G. et al. Benefit from letrozole as extended adjuvant therapy after sequential endocrine therapy: A randomized, phase III study of Gruppo Italiano Mammella (GIM). 2019 ASCO Annual Meeting; Abstr. 504.
    Google Scholar
  • 35 Blok EJ, Kroep JR, Meershoek-Klein Kranenbarg E. et al. Optimal Duration of Extended Adjuvant Endocrine Therapy for Early Breast Cancer; Results of the IDEAL Trial (BOOG 2006-05). J Natl Cancer Inst 2018; 110
    Google Scholar