Adjuvante Endokrine Therapie des Mammakarzinoms – Standards und neue Daten

 

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Das Hormonrezeptor-positive Mammakarzinom macht den größten Anteil aller frühen Mammkarzinome aus. Bei prämenopausalen Patientinnen ist Tamoxifen Therapie der Wahl, Aromataseinhibitoren sind aufgrund der ovariellen Aktivität kontraindiziert. In der postmenopausalen Situation werden neben Tamoxifen auch Aromataseinhibitoren eingesetzt. Diese können als initiale Therapie für 5 Jahre, als Sequenztherapie nach 2–3 Jahren Tamoxifen oder als erweiterte Endokrine Therapie nach 5 Jahren Tamoxifen eingesetzt werden. Aktuell ist allerdings die Frage nach der optimalen Therapie der prämenopausalen Patientin im Fokus des Interesses. Welche Patientin sollte eine 10-jährige Tamoxifentherapie und welche eine Therapie mit einem Aromataseinhibitor in Kombination mit einem Gonadotropin Releasing Hormon(GnRH)-Analogon erhalten? Neue Daten, die in den vergangenen 2–3 Jahren publiziert wurden, zeigen einen Benefit durch die Kombination eines Aromataseinhibitors mit GnRH-Analogon und durch die Erweiterung einer Tamoxifentherapie auf 10 Jahre. Dieser Artikel soll zum einen die Standards in der endokrinen Therapie beschreiben, zum anderen aber auch die neuen Daten in einen aktuellen Kontext bringen.

Hormone receptor-positive breast cancers represent the vast majority of early breast cancers. In premenopausal patients tamoxifen is the treatment of choice as aromatase inhibitors are contraindicated due to the endocrine activity of premenopausal patients. In postmenopausal patients aromatase inhibitors are included in the endocrine treatment. Aromatase inhibitors can be used as an initial treatment for 5 years, as sequential treatment after 2–3 years of tamoxifen or as an extended endocrine treatment after 5 years of tamoxifen. However, the optimal treatment of premenopausal patients is currently in the focus of interest. Which patient should undergo a 10-year treatment with tamoxifen and which patient should be treated with a combination of an aromatase inhibitor and a luteinizing hormone-relaesing hormone (LHRH) agonist? New data that had been published in the last 2-3 years presented beneficial results by using a combination of an aromatase inhibitor and a luteinizing hormone-releasing hormone (LHRH) agonist, moreover by utilizing a tamoxifen treatment of 10 years. The aim of this article is to describe the standard of care in endocrine treatment and to put the new data in the right context.

• Literatur

• 1 Davies C, Godwin J, Gray R et al. Early Breast Cancer Trialists' Collaborative Group (EBCTCG). 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
• 2 Fisher B, Dignam J, Bryant J, Wolmark N. Five versus more than five years of tamoxifen for lymph node-negative breast cancer: updated findings from the National Surgical Adjuvant Breast and Bowel Project B-14 randomized trial. J Natl Cancer Inst 2001; 93: 684-690
  CrossrefPubMedGoogle Scholar
• 3 Davies C, Pan H, Godwin J et al. Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) Collaborative Group. 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
• 4 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 (suppl; abstr 5) 2013; 31
  PubMedGoogle Scholar
• 5 Cuzick J, Ambroisine L, Davidson N et al. LHRH-agonists in Early Breast Cancer Overview group Use of luteinising-hormone-releasing hormone agonists as adjuvant treatment in premenopausal patients with hormone-receptor-positive breast cancer: a meta-analysis of individual patient data from randomised adjuvant trials. Lancet 2007; 369: 1711-1723
  CrossrefPubMedGoogle Scholar
• 6 Pagani O, Regan MM, Walley BA et al. TEXT and SOFT Investigators, International Breast Cancer Study Group. Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. N Engl J Med 2014; 371: 107-118
  CrossrefPubMedGoogle Scholar
• 7 Francis PA, Regan MM, Fleming GF et al. SOFT Investigators and the International Breast Cancer Study Group. Adjuvant Ovarian Suppression in Premenopausal Breast Cancer. N Engl J Med 2014 Dec 11 [Epub ahead of print] 2014;
  PubMedGoogle Scholar
• 8 Regan MM, Neven P, Giobbie-Hurder A et al. BIG 1-98 Collaborative Group, International Breast Cancer Study Group (IBCSG). 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
• 9 Goss PE, Ingle JN, Martino S et al. Impact of premenopausal status at breast cancer diagnosis in women entered on the placebo-controlled NCIC CTG MA17 trial of extended adjuvant letrozole. Ann Oncol 2013; 24: 355-361
  CrossrefPubMedGoogle Scholar
• 10 Cuzick J, Sestak I, Baum M et al. ATAC/LATTE investigators. 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
• 11 Dubsky PC, Jakesz R, Mlineritsch B et al. Tamoxifen and anastrozole as a sequencing strategy: a randomized controlled trial in postmenopausal patients with endocrine-responsive early breast cancer from the Austrian Breast and Colorectal Cancer Study Group. J Clin Oncol 2012; 30: 722-728
  CrossrefPubMedGoogle Scholar
• 12 Goss PE, Ingle JN, Pater JL et al. Late extended adjuvant treatment with letrozole improves outcome in women with early-stage breast cancer who complete 5 years of tamoxifen. J Clin Oncol 2008; 26: 1948-1955
  CrossrefPubMedGoogle Scholar
• 13 Hadji P, Body JJ, Aapro MS et al. Practical guidance for the management of aromatase inhibitor-associated bone loss. Ann Oncol 2008; 19: 1407-1416
  CrossrefPubMedGoogle Scholar