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DOI: 10.1055/s-0032-1315131
Breast Cancer 2012 – New Aspects
Mammakarzinom 2012 – neue AspektePublikationsverlauf
received 18. Juni 2012
revised 23. Juni 2012
accepted 23. Juni 2012
Publikationsdatum:
31. Juli 2012 (online)
Abstract
Treatment options as well as the characteristics for therapeutic decisions in patients with primary and advanced breast cancer are increasing in number and variety. New targeted therapies in combination with established chemotherapy schemes are broadening the spectrum, however potentially promising combinations do not always achieve a better result. New data from the field of pharmacogenomics point to prognostic and predictive factors that take not only the properties of the tumour but also inherited genetic properties of the patient into consideration. Current therapeutic decision-making is thus based on a combination of classical clinical and modern molecular biomarkers. Also health-economic aspects are more frequently being taken into consideration so that health-economic considerations may also play a part. This review is based on information from the recent annual congresses. The latest of these are the 34th San Antonio Breast Cancer Symposium 2011 and the ASCO Annual Meeting 2012. Among their highlights are the clinically significant results from the CLEOPATRA, BOLERO-2, EMILIA and SWOG S0226 trials on the therapy for metastatic breast cancer as well as further state-of-the-art data on the adjuvant use of bisphosphonates within the framework of the ABCSG-12, ZO-FAST, NSABP-B34 and GAIN trials.
Zusammenfassung
Die Behandlungsoptionen und auch die Charakteristika zur Therapieentscheidung der Patientin mit einem primären und fortgeschrittenen Mammakarzinom werden immer vielfältiger. Neue zielgerichtete Therapien in Kombination mit etablierten Chemotherapien erweitern das Spektrum, doch potenziell vielversprechende Kombinationen bringen nicht immer ein besseres Ergebnis. Neueste Daten aus der Pharmakogenomik weisen auf Prognose- und Prädiktivfaktoren hin, die nicht nur die Eigenschaften des Tumors, sondern auch die vererbbaren genetischen Eigenschaften der Patientin berücksichtigen. Die aktuelle Therapieentscheidung ist somit mittlerweile eine Kombination aus klassischerweise klinischen und modernen molekularen Biomarkern. Immer häufiger werden auch gesundheitsökonomische Aspekte berücksichtigt, sodass auch gesundheitspolitische Überlegungen eine Rolle spielen können. Dieser Übersichtsartikel baut auf den aktuellen Kongressen auf, die jedes Jahr stattfinden. Die letzten berücksichtigten sind hierbei das 34. San Antonio Breast Cancer Symposium und das ASCO Annual Meeting 2012. Zu deren Highlights zählten die klinisch bedeutsamen Ergebnisse der Studien CLEOPATRA, BOLERO-2, EMILIA und SWOG S0226 zur Therapie des metastasierten Mammakarzinoms sowie weitere aktuelle Daten zum adjuvanten Einsatz der Bisphosphonate im Rahmen der Studien ABCSG-12, ZO-FAST, NSABP-B34 und GAIN.
Key words
CLEOPATRA - pertuzumab - BOLERO-2 - everolimus - EMILIA - TDM-1 - ABCSG-12 - ZO-FAST - NSABP-B34 - GAINSchlüsselwörter
CLEOPATRA - Pertuzumab - BOLERO-2 - Everolimus - EMILIA - TDM-1 - ABCSG-12 - ZO-FAST - NSABP-B34 - GAIN-
References
- 1 Fasching PA, Fehm T, Janni W et al. Breast cancer therapy – a state of the art review. Geburtsh Frauenheilk 2010; 70: 875-886
- 2 Kummel S, Kolberg HC, Luftner D et al. Breast cancer 2011 – new aspects. Geburtsh Frauenheilk 2011; 71: 939-953
- 3 Fisher B, Anderson S, Bryant J et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med 2002; 347: 1233-1241
- 4 Veronesi U, Cascinelli N, Mariani L et al. Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med 2002; 347: 1227-1232
- 5 Bani HA, Fasching PA, Lux MM et al. Lymphedema in breast cancer survivors: assessment and information provision in a specialized breast unit. Patient education and counseling 2007; 66: 311-318
- 6 Veronesi U, Paganelli G, Viale G et al. A randomized comparison of sentinel-node biopsy with routine axillary dissection in breast cancer. N Engl J Med 2003; 349: 546-553
- 7 Kühn T. Mammakarzinom. Stellenwert des axillären Stagings. Gynäkologe 2011; 44: 999-1004
- 8 Galimberti V, Cole BF, Zurrida S et al. Update of International Breast Cancer Study Group trial 23-01 to compare axillary dissection versus no axillary dissection in patients with clinically node negative breast cancer and micrometastases in the sentinel node. Cancer Res 2011; 71: 102s
- 9 Moebus V, Jackisch C, Lueck HJ et al. Intense dose-dense sequential chemotherapy with epirubicin, paclitaxel, and cyclophosphamide compared with conventionally scheduled chemotherapy in high-risk primary breast cancer: mature results of an AGO phase III study. J Clin Oncol 2010; 28: 2874-2880
- 10 Engel J, Lebeau A, Sauer H et al. Are we wasting our time with the sentinel technique? Fifteen reasons to stop axilla dissection. Breast 2006; 15: 452-455
- 11 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
- 12 Krag DN, Anderson SJ, Julian TB et al. Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically node-negative patients with breast cancer: overall survival findings from the NSABP B-32 randomised phase 3 trial. Lancet Oncol 2010; 11: 927-933
- 13 Arbeitsgemeinschaft für Gynäkologische Onkologie e.V.. AGO Guidelines. http://www.ago-online.org last access: 2012
- 14 Veronesi U, Orecchia R, Luini A et al. Intraoperative radiotherapy during breast conserving surgery: a study on 1,822 cases treated with electrons. Breast Cancer Res Treat 2010; 124: 141-151
- 15 Vaidya JS, Baum M, Tobias JS et al. Long-term results of targeted intraoperative radiotherapy (Targit) boost during breast-conserving surgery. Int J Radiat Oncol, Biol, Phys 2011; 81: 1091-1097
- 16 Smith GL, Xu Y, Buchholz TA et al. Partial breast brachytherapy is associated with inferior effectiveness and increased toxicity compared with whole breast irradiation in older patients. Cancer Res 2011; 71: 99s
- 17 Cutuli B, Cohen-Solal-le Nir C, de Lafontan B et al. Breast-conserving therapy for ductal carcinoma in situ of the breast: the French Cancer Centersʼ experience. Int J Radiat Oncol, Biol, Phys 2002; 53: 868-879
- 18 Clarke M, Collins R, Darby S et al. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005; 366: 2087-2106
- 19 Bijker N, Meijnen P, Peterse JL et al. Breast-conserving treatment with or without radiotherapy in ductal carcinoma-in-situ: ten-year results of European Organisation for Research and Treatment of Cancer randomized phase III trial 10853 – a study by the EORTC Breast Cancer Cooperative Group and EORTC Radiotherapy Group. J Clin Oncol 2006; 24: 3381-3387
- 20 Hughes LL, Wang M, Page DL et al. Local excision alone without irradiation for ductal carcinoma in situ of the breast: a trial of the Eastern Cooperative Oncology Group. J Clin Oncol 2009; 27: 5319-5324
- 21 Solin LJ, Gray R, Baehner FL et al. A quantitative multigene RT-PCR assay for predicting recurrence risk after surgical excision alone without irradiation for ductal carcinoma in situ (DCIS): a prospective validation study of the DCIS score from ECOG E5194. Cancer Res 2011; 71: 108s
- 22 Untch M, von Minckwitz G. Neoadjuvant treatment of breast cancer. Breast Care (Basel) 2011; 6: 417
- 23 von Minckwitz G, Eidtmann H, Rezai M et al. Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer. N Engl J Med 2012; 366: 299-309
- 24 Untch M, Loibl S, Bischoff J et al. Lapatinib versus trastuzumab in combination with neoadjuvant anthracycline-taxane-based chemotherapy (GeparQuinto, GBG 44): a randomised phase 3 trial. Lancet Oncol 2012; 13: 135-144
- 25 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
- 26 von Minckwitz G, Untch M, Nuesch E et al. Impact of treatment characteristics on response of different breast cancer phenotypes: pooled analysis of the German neo-adjuvant chemotherapy trials. Breast cancer research and treatment 2011; 125: 145-156
- 27 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;
- 28 Gianni L, Bianchini G, Kiermaier A et al. Neoadjuvant pertuzumab and trastuzumab: biomarker analyses of a 4-arm randomized phase II study (NeoSphere) in patients with HER2-positive breast cancer. Cancer Res 2011; 71: 109s-110s
- 29 Gianni L, Pienkowski T, Im YH et al. 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 2012; 13: 25-32
- 30 Schneeweiss A, Chia S, Hickish T et al. Neoadjuvant pertuzumab and trastuzumab concurrent or sequential with an anthracycline-containing or concurrent with an anthracycline-free standard regimen: A randomized phase II study (TRYPHAENA). Cancer Res 2011; 71: 112s-113s
- 31 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
- 32 Liedtke C, Mazouni C, Hess KR et al. Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol 2008; 26: 1275-1281
- 33 Loibl S, von Minckwitz G, Blohmer JU et al. pCR as a surrogate in HER2-positive patients treated with trastuzumab. Cancer Res 2011; 71: 111s
- 34 Cheang MCU, Prat A, Fan C et al. PAM50 HER2-enriched subtype enriches for tumor response to neoadjuvant anthracyclines/taxane and trastuzumab/taxane containing regimens in HER2-positive breast cancer. Cancer Res 2011; 71: 110s
- 35 von Minckwitz G, Kümmel S, Vogel P et al. Neoadjuvant vinorelbine–capecitabine versus docetaxel–doxorubicin–cyclophosphamide in early nonresponsive breast cancer: phase III randomized GeparTrio trial. J Natl Cancer Inst 2008; 100: 542-551
- 36 Goldhirsch A, Wood WC, Coates AS et al. Strategies for subtypes – dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Ann Oncol 2011; 22: 1736-1747
- 37 von Minckwitz G, Eidtmann H, Loibl S et al. Integrating bevacizumab, everolimus, and lapatinib into current neoadjuvant chemotherapy regimen for primary breast cancer. Safety results of the GeparQuinto trial. Ann Oncol 2011; 22: 301-306
- 38 Huober J, Hanusch C, Fasching PA et al. Neoadjuvant chemotherapy of paclitaxel with or without Rad001: results of the non-responder part of the GEPARQUINTO study (GBG 44). Cancer Res 2011; 71: 105s
- 39 Gnant M, Mlineritsch B, Schippinger W et al. Endocrine therapy plus zoledronic acid in premenopausal breast cancer. N Engl J Med 2009; 360: 679-691
- 40 Gnant M, Mlineritsch B, Luschin-Ebengreuth G et al. Long-term follow-up in ABCSG-12: significantly improved overall survival with adjuvant zoledronic acid in postmenopausal patients with endocrine-receptor-positive early breast cancer. Cancer Res 2011; 71: 95s-96s
- 41 de Boer R, Bundred N, Eidtmann H et al. Long-term survival outcomes among postmenopausal women with hormone receptor-positive early breast cancer receiving adjuvant letrozole and zoledronic acid: 5-year follow-up of ZO-FAST. Cancer Res 2011; 71: 96s
- 42 Coleman RE, Marshall H, Cameron D et al. Breast-cancer adjuvant therapy with zoledronic acid. N Engl J Med 2011; 365: 1396-1405
- 43 Diel IJ, Jaschke A, Solomayer EF et al. Adjuvant oral clodronate improves the overall survival of primary breast cancer patients with micrometastases to the bone marrow: a long-term follow-up. Ann Oncol 2008; 19: 2007-2011
- 44 Powles T, Paterson S, Kanis JA et al. Randomized, placebo-controlled trial of clodronate in patients with primary operable breast cancer. J Clin Oncol 2002; 20: 3219-3224
- 45 Paterson AHG, Anderson SJ, Lembersky BC et al. NSABP protocol B-34: a clinical trial comparing adjuvant clodronate vs. placebo in early stage breast cancer patients receiving systemic chemotherapy and/or tamoxifen or no therapy – final analysis. Cancer Res 2011; 71: 100s
- 46 Moebus V, Thomssen C, Harbeck N et al. Gain (German Adjuvant Intergroup Node Positive) study: a phase-III multicenter trial to compare dose dense, dose intense ETC (iddETC) vs. EC-TX and Ibandronate vs. observation in patients with node-positive primary breast cancer – 1st interim efficacy analysis. Cancer Res 2011; 71: 6s
- 47 Janni WJ, Harbeck N, Sommer H et al. Sequential treatment with epirubicin/cyclophosphamide, followed by docetaxel vs. FEC120 in the adjuvant treatment of breast cancer patients with extensive lymph node involvement: final survival analysis of the German ADEBAR phase III study. Cancer Res 2011; 71: 140s
- 48 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
- 49 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 standard-dosed epirubicin-cyclophosphamide followed by paclitaxel with or without darbepoetin alfa in primary breast cancer – outcome on prognosis. Ann Oncol 2011; 22: 1999-2006
- 50 Nitz U, Gluz O, Oberhoff C et al. Adjuvant chemotherapy with or without darbepoetin alpha in node-positive breast cancer: survival and quality of life analysis from the prospective randomized WSG ARA plus trial. Cancer Res 2011; 71: 143s
- 51 Goss P, Smith I, OʼShaugnessy J et al. Results of a randomized, double-blind, multicenter, placebo-controlled study of adjuvant lapatinib in women with early-stage ErbB2-overexpressing breast cancer. Cancer Res 2011; 71: 109s
- 52 Baselga J, Cortes J, Kim SB et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med 2012; 366: 109-119
- 53 Saura C, Garcia-Saenz JA, Xu B et al. Safety and efficacy of neratinib in combination with capecitabine in patients with ErbB2-positive breast cancer. Cancer Res 2011; 71: 225s
- 54 Gianni L, Romieu G, Lichinitser M et al. First results of AVEREL, a randomized phase III trial to evaluate bevacizumab (BEV) in combination with trastuzumab (H) + docetaxel (DOC) as first-line therapy for HER2-positive locally recurrent/metastatic breast cancer (LR/mBC). Cancer Res 2011; 71: 109s
- 55 Blackwell KL, Miles D, Gianni L et al. Primary results from EMILIA, a phase III study of trastuzumab emtansine (T-DM1) versus capecitabine (X) and lapatinib (L) in HER2-positive locally advanced or metastatic breast cancer (MBC) previously treated with trastuzumab (T) and a taxane. J Clin Oncol 2012; 30 (suppl; abstr 512)
- 56 Xu B, Guan ZZ, Shen ZZ et al. Association of PTEN loss and PIK3CA mutations on outcome in HER2+ metastatic breast cancer patients treated with first-line lapatinib plus paclitaxel or paclitaxel alone. Cancer Res 2011; 71: 103s-104s
- 57 Colleoni M, Giobbie-Hurder A, Regan MM et al. Analyses adjusting for selective crossover show improved overall survival with adjuvant letrozole compared with tamoxifen in the BIG 1-98 study. J Clin Oncol 2011; 29: 1117-1124
- 58 Paridaens RJ, Dirix LY, Beex LV et al. The European Organisation for Research and Treatment of Cancer Breast Cancer Cooperative Group. Phase III study comparing exemestane with tamoxifen as first-line hormonal treatment of metastatic breast cancer in postmenopausal women. J Clin Oncol 2008; 26: 4883-4890
- 59 Mouridsen H, Gershanovich M, Sun Y et al. Phase III study of letrozole versus tamoxifen as first-line therapy of advanced breast cancer in postmenopausal women: analysis of survival and update of efficacy from the International Letrozole Breast Cancer Group. J Clin Oncol 2003; 21: 2101-2109
- 60 Nabholtz JM, Bonneterre J, Buzdar A et al. Anastrozole (Arimidex) versus tamoxifen as first-line therapy for advanced breast cancer in postmenopausal women: survival analysis and updated safety results. Eur J Cancer 2003; 39: 1684-1689
- 61 Bergh J, Jonsson PE, Lidbrink EK et al. FACT: an open-label randomized phase III study of fulvestrant and anastrozole in combination compared with anastrozole alone as first-line therapy for patients with receptor-positive postmenopausal breast cancer. J Clin Oncol 2012;
- 62 Mehta RS, Barlow WE, Albain KS et al. A Phase III randomized trial of anastrozole versus anastrozole and fulvestrant as first-line therapy for postmenopausal women with metastatic breast cancer: SWOG S0226. Cancer Res 2011; 71: 95s
- 63 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
- 64 Piccart-Gebhart MJ, Noguchi S, Pritchard KI et al. Everolimus for postmenopausal women with advanced breast cancer: Updated results of the BOLERO-2 phase III trial. J Clin Oncol 2012; 30 (suppl; abstr 559)
- 65 Statistisches Bundesamt. Gesundheit – Ausgaben (Lange Reihe) – Fachserie 12, Reihe 7.1.2 – 1995 bis 2012. Erschienen am 05.04.2012. Artikelnummer: 2120712107004
- 66 Lux MP, Fasching PA, Loehberg CR et al. Health services research and health economy – quality care training in gynaecology, with focus on gynaecological oncology. Geburtsh Frauenheilk 2011; 71: 1046-1055
- 67 Mariotto AB, Yabroff KR, Shao Y et al. Projections of the cost of cancer care in the United States: 2010–2020. J Natl Cancer Inst 2011; 103: 117-128
- 68 Chereau E, Vataire AL, Laas E et al. Economic analysis of chemotherapy costs for adjuvant therapy in breast cancer in France. Cancer Res 2011; 71: 214s-215s
- 69 Baffert S, Cottu PH, Kirova Y et al. Burden of brain metastases in HER2-positive breast cancer: healthcare use and costs from a French observational retrospective multicenter study. Cancer Res 2011; 71: 212s-213s
- 70 Reed SD, Li Y, Anstrom KJ et al. Cost effectiveness of ixabepilone plus capecitabine for metastatic breast cancer progressing after anthracycline and taxane treatment. J Clin Oncol 2009; 27: 2185-2191
- 71 Centers for Medicare & Medicaid Services, Office of the Actuary. Updated national health expenditure projections 2009–2019. https://www.cmsgov/Research-Statistics-Data-and-Systems/Statistics-Trends-and-Reports/NationalHealthExpendData/downloads/proj2009pdf last access: September 2011
- 72 Hershman DL, Neugut AI, Richards CA et al. Influence of hospital factors, physician factors and type of health insurance on receipt of immediate postmastectomy reconstruction in young women with breast cancer. Cancer Res 2011; 71: 114s-115s
- 73 Neumann PJ, Palmer JA, Nadler E et al. Cancer therapy costs influence treatment: a national survey of oncologists. Health Affairs 2010; 29: 196-202
- 74 Lacey L, Chien R, Hornberger J. Cost-utility of the 21-gene breast cancer assay (Oncotype DX®) in the Irish healthcare setting. Cancer Res 2011; 71: 213s
- 75 Pronzato P, Plun-Favreau J. Is the 21-gene breast cancer test (Oncotype DX®) cost-effective?. Cancer Res 2011; 71: 213s-214s
- 76 Warren JL, Yabroff KR, Meekins A et al. Evaluation of trends in the cost of initial cancer treatment. J Natl Cancer Inst 2008; 100: 888-897
- 77 von Minckwitz G, Blohmer JU, Costa SD et al. Neoadjuvant chemotherapy adapted by interim response improves overall survival of primary breast cancer patients – results of the GeparTrio trial. Cancer Res 2011; 71: 103s