Zusammenfassung
Der konsequente, nach Rezeptorstatus und HER2-Expression differenzierte Einsatz medikamentöser (neo-)adjuvanter Therapien hat wesentlichen Anteil an der verbesserten Prognose beim operablen Mammakarzinom. Bei rezeptorpositiver Erkrankung sind 5 Jahre endokrine Therapie (Tamoxifen, Aromatasehemmer) Standard, die Verlängerung auf 10 Jahre kann die langfristige Prognose weiter verbessern. Bei der (neo-)adjuvanten Chemotherapie sind Anthrazykline und Taxane erste Wahl, bevorzugt in dosisdichten Regimen. Bei positivem HER2-Status ist die Kombination mit Trastuzumab obligat. Ist eine adjuvante Chemotherapie geplant, soll immer – insbesondere bei HER2-positivem Status und bei TNBC – die Option einer neoadjuvanten Therapie geprüft werden. Für postmenopausale Patientinnen ist die adjuvante Therapie mit Bisphosphonaten möglicherweise von Nutzen. In der metastasierten hormonsensiblen Situation stehen unverändert endokrine Therapien an erster Stelle. In der Second-line-Therapie ergeben sich durch Fulvestrant und durch die Kombination Exemestan/Everolimus neue Optionen. Hinsichtlich der Chemotherapie werden auch in der metastasierten Situation als erstes Taxane oder Anthrazykline eingesetzt. Typische Second-line-Substanzen sind Vinorelbin, Capecitabin und Eribulin. In Risikofällen kann Bevacizumab eine Ergänzung sein. Bei Knochenmetastasen sollen, unabhängig von der spezifischen Tumortherapie, frühzeitig Bisphosphonate oder Denosumab eingesetzt werden. Zur Prävention bei gesunden postmenopausalen Frauen mit erhöhtem Brustkrebsrisiko (10-Jahres-Erkrankungsrisiko über 5 %) können Aromatasehemmer eingesetzt werden. Eine Beratung hinsichtlich des Lebensstils muss in die Nutzen-Risiko-Abwägung einbezogen werden.
Abstract
The improved prognosis of early breast cancer results from the consequent use of systemic (neo) adjuvant therapy that is individually guided mainly by the expression of steroid hormone receptors and HER2. In hormone receptor positive disease, 5 years of endocrine therapy (e.g. tamoxifen or aromatase inhibitors) represents the standard and prolongation up to 10 years may further improve the long-term prognosis. In (neo) adjuvant chemotherapy, anthracyclines and taxanes are the first choice and a dose-dense regimen is an effective option. In HER2 positive disease the combination with trastuzumab is mandatory. If chemotherapy is planned a neoadjuvant regimen should be considered particularly in HER2 positive cancer and triple negative breast cancer (TNBC). In postmenopausal patients, bisphosphonates may be considered as an additional adjuvant therapy. If metastases have been found the use of endocrine treatment is still the first line treatment in hormone sensitive disease. In second line therapy the treatment options are fulvestrant or a combination of exemestane and everolimus. With regard to chemotherapy taxanes and anthracyclines are considered first choice also for metastatic breast cancer and for second line therapy vinorelbine, capecitabine and eribulin are typically employed. In high risk situations, bevacizumab is an additional option. With the occurrence of metastases, bisphosphonates or denosumab should be given independently from any specific treatment. In healthy postmenopausal women with an elevated risk of breast cancer (> 5 % within 10 years), aromatase inhibitors can be given as chemoprevention. Women should be comprehensively advised in order to weigh the risks and benefits of chemoprevention and options for lifestyle changes.
Literatur
AGO recommendations (2014) Diagnosis and treatment of patients with primary and metastatic breast cancer. http://www.ago-online.de. Zugegriffen: 31. März 2014
Minckwitz G von, Untch M, Blohmer JU et al (2012) Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol 30:1796–1804
Early Breast Cancer Trialists‘ Collaborative Group (2005) Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 365:1687–1717
Strasser-Weippl K, Badovinac-Crnjevic T, Fan L et al (2013) Extended adjuvant endocrine therapy in hormone-receptor positive breast cancer. Breast 22(Suppl 2):S171–S175
Davies C, Pan H, Godwin J et al (2013) 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 381:805–816
NCCN clinical practice guidelines in oncology (NCCN Guidelines)®. Breast cancer. Version 3.2014. Zugegriffen: 28. Apr. 2014
Budd GT, Barlow WE, Moore CF et al (2013) S0221: comparison of two schedules of paclitaxel as adjuvant therapy for breast cancer. J Clin Oncol 31(Suppl):abstr CRA1008
Moebus VJ, Jackisch C, Lueck HJ et al (2010) Intense dose-dense sequential chemotherapy with epirubicin, paclitaxel and cyclophosphamide compared with conventionally scheduled chemotherapy in high-risk breast cancer patients (≥ 4 + LN): mature results of an AGO-phase-III study. J Clin Oncol 28:2874–2880
Moja L, Tagliabue L, Balduzzi S et al (2012) Trastuzumab containing regimens for early breast cancer. Cochrane Database Syst Rev 4:CD006243
Gianni L, Pienkowski T, Im YH et al (2012) Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol 13:25–32
Baselga J, Bradbury I, Eidtmann H et al (2012) Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet 379:633–640
Tolaney SM, Barry WT, Dang CT et al (2013) A phase II study of adjuvant paclitaxel (T) and trastuzumab (H) (APT trial) for node-negative, HER2-positive breast cancer (BC). San Antonio Breast Cancer Symposium S1-04
Masuda H, Baggerly KA, Wang Y et al (2013) Comparison of molecular subtype distribution in triple-negative inflammatory and non-inflammatory breast cancers. Breast Cancer Res 15:R112
Cortazar P, Zhang L, Untch M et al (2014) Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet pii: S0140-6736(13)62422-8
Minckwitz G von, Schneeweiss A, Salat C et al (2013) A randomized phase II trial investigating the addition of carboplatin to neoadjuvant therapy for triple-negative and HER2-positive early breast cancer (GeparSixto). J Clin Oncol 31(Suppl):abstr 1004
Sikov WM, Berry DA, Perou CM et al (2013) Impact of the addition of carboplatin (Cb) and/or bevacizumab (B) to neoadjuvant weekly paclitaxel (P) followed by dose-dense AC on pathologic complete response (pCR) rates in triple-negative breast cancer (TNBC): CALGB 40603 (Alliance). San Antonio Breast Cancer Symposium: S5-01
Schlitt A, Jordan K, Vordermark D et al (2014) Kardiotoxizität onkologischer Therapien. Dtsch Arztebl Int 111:161–168
Cardoso F, Costa A, Norton L et al (2012) 1st International consensus guidelines for advanced breast cancer (ABC 1). Breast 21:242–252
Di Leo A, Jerusalem G, Petruzelka L et al (2014) Final overall survival: fulvestrant 500 mg vs 250 mg in the randomized CONFIRM trial. J Natl Cancer Inst 106:djt337
Baselga J, Campone M, Piccart M et al (2012) Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med 366:520–529
Baselga J, Cortés J, Kim SB et al (2012) Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med 366:109–119
Swain SM, Kim SB, Cortés J et al (2013) Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol 14:461–471
Verma S, Miles D, Gianni L et al (2013) Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med 367:1783–1791
Wagner AD, Thomssen C, Haerting J, Unverzagt S (2012) Vascular-endothelial-growth-factor (VEGF) targeting therapies for endocrine refractory or resistant metastatic breast cancer. Cochrane Database Syst Rev 7:CD008941
Henry D, Vadhan-Raj S, Hirsh V et al (2014) Delaying skeletal-related events in a randomized phase 3 study of denosumab versus zoledronic acid in patients with advanced cancer: an analysis of data from patients with solid tumors. Support Care Cancer 22:679–687
Coleman R, Gnant M, Paterson A et al (2013) Effects of bisphosphonate treatment on recurrence and cause-specific mortality in women with early breast cancer: a meta-analysis of individual patient data from randomised trials. San Antonio Breast Cancer Symposium S4-07
Goss PE, Ingle JN, Alés-Martínez JE et al (2011) NCIC CTG MAP.3 study investigators. Exemestane for breast-cancer prevention in postmenopausal women. N Engl J Med 364:2381–2391
Cuzick J, Sestak I, Forbes JF et al (2014) IBIS-II investigators. Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): an international, double-blind, randomised placebo-controlled trial. Lancet 383:1041–1048
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Interessenkonflikt. C. Thomssen weist auf folgende Beziehungen hin: Honorare für Vorträge und Advisory Boards von Amgen, Cellgena, Glaxo Smith Kline, Novartis, Roche, Teva. Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.
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Thomssen, C. Pharma Update Mammakarzinom. Gynäkologe 47, 482–489 (2014). https://doi.org/10.1007/s00129-013-3285-9
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DOI: https://doi.org/10.1007/s00129-013-3285-9