Update Mammakarzinom 2019 Teil 3 – aktuelle Entwicklungen bei der kurativen Behandlung von Mammakarzinompatientinnen: eine Übersicht und Bewertung durch ein internationales Expertenpanel

Zusammenfassung

Die Behandlung von Mammakarzinompatientinnen in der kurativen Situation ist in vielfacher Hinsicht besonders. Hierbei ist die lokale Therapie mit Operation und Strahlentherapie zentraler Aspekt der Behandlung. Ziel ist eine komplette Elimination aller Tumorzellen am Ort der Primärerkrankung bei gleichzeitigem Bestreben, die Langzeitfolgen so gering wie möglich zu halten. Die immer weitere Reduktion der Radikalität der Lokaltherapie steht auch weiterhin im Blickpunkt. In Bezug auf die Systemtherapie haben sich in den letzten beiden Jahrzehnten Chemotherapien mit Taxanen, Anthrazyklinen und teilweise auch platinhaltigen Chemotherapien etabliert. Der Kontext der Nutzung wird immer genauer definiert. Ebenso gibt es bei der antihormonellen Therapie Fragen, die auch nach Einführung der Aromatasehemmer immer noch weiter definiert werden müssen, wie beispielsweise die Länge der Therapie oder die ovarielle Suppression bei prämenopausalen Patientinnen. Letztendlich soll die Behandlung von frühen Mammakarzinompatientinnen immer personalisierter werden. Prognostische genexpressionistische Tests könnten möglicherweise Therapieentscheidungen unterstützen. Ebenso muss überlegt werden, wie ein möglicher Einsatz von neuen Therapien wie Checkpointinhibitoren und CDK4/6-Inhibitoren in der Praxis aussehen könnten, sobald hier Studienergebnisse vorliegen. Diese Übersichtsarbeit beschäftigt sich mit den Hintergründen zu aktuellen Abstimmungen, die das internationale St.-Gallen-Expertenpanel in Wien 2019 für aktuelle Fragen in der Behandlung von Mammakarzinompatientinnen in der kurativen Situation vorgenommen hat.

Schlüsselwörter

frühes Mammakarzinom - adjuvante Therapie - neoadjuvante Therapie - St.-Gallen-Expertenpanel

• References/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
• 2 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 2 with Recommendations for the Therapy of Primary, Recurrent and Advanced Breast Cancer. Geburtsh Frauenheilk 2018; 78: 1056-1088
• 3 Kreienberg R, Wockel A, Wischnewsky M. Highly significant improvement in guideline adherence, relapse-free and overall survival in breast cancer patients when treated at certified breast cancer centres: An evaluation of 8323 patients. Breast 2018; 40: 54-59
• 4 Brennan M, Gass P, Haberle L. et al. The effect of participation in neoadjuvant clinical trials on outcomes in patients with early breast cancer. Breast Cancer Res Treat 2018; DOI: 10.1007/s10549-018-4829-4.
• 5 Brennan MB, Gass P, Häberle L. et al. The effect of participation in neoadjuvant clinical trials on outcomes in patients with early breast cancer. Breast Cancer Res Treat 2018; 171: 747-758
• 6 Schwentner L, Van Ewijk R, Kurzeder C. et al. Participation in adjuvant clinical breast cancer trials: does study participation improve survival compared to guideline adherent adjuvant treatment? A retrospective multi-centre cohort study of 9,433 patients. Eur J Cancer 2013; 49: 553-563
• 7 Beckmann MW, Brucker C, Hanf V. et al. Quality assured health care in certified breast centers and improvement of the prognosis of breast cancer patients. Onkologie 2011; 34: 362-367
• 8 Kommission Mamma der Arbeitsgemeinschaft Gynäkologische Onkologie e.V. in der Deutschen Gesellschaft für Gynäkologie und Geburtshilfe e.V. sowie in der Deutschen Krebsgesellschaft e.V.. Diagnostik und Therapiefrüher und fortgeschrittener Mammakarzinome. 2019. https://www.ago-online.de/de/infothek-fuer-aerzte/leitlinienempfehlungen/mamma/ last access: 27.03.2019
• 9 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
• 10 Couch FJ, Shimelis H, Hu C. et al. Associations Between Cancer Predisposition Testing Panel Genes and Breast Cancer. JAMA Oncol 2017; 3: 1190-1196
• 11 Mavaddat N, Michailidou K, Dennis J. et al. Polygenic Risk Scores for Prediction of Breast Cancer and Breast Cancer Subtypes. Am J Hum Genet 2018; DOI: 10.1016/j.ajhg.2018.11.002.
• 12 Shimelis H, LaDuca H, Hu C. et al. Triple-Negative Breast Cancer Risk Genes Identified by Multigene Hereditary Cancer Panel Testing. J Natl Cancer Inst 2018; DOI: 10.1093/jnci/djy106.
• 13 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
• 14 Michailidou K, Lindstrom S, Dennis J. et al. Association analysis identifies 65 new breast cancer risk loci. Nature 2017; 551: 92-94
• 15 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
• 16 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 361e1–361e2
• 17 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
• 18 Varghese JS, Easton DF. Genome-wide association studies in common cancers–what have we learnt?. Curr Opin Genet Dev 2010; 20: 201-209
• 19 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
• 20 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
• 21 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
• 22 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
• 23 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
• 24 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
• 25 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
• 26 Stevens KN, Vachon CM, Lee AM. et al. Common breast cancer susceptibility loci are associated with triple-negative breast cancer. Cancer Res 2011; 71: 6240-6249
• 27 Litton JK, Rugo HS, Ettl J. et al. Talazoparib in Patients with Advanced Breast Cancer and a Germline BRCA Mutation. N Engl J Med 2018; 379: 753-763
• 28 Robson M, Im SA, Senkus E. et al. Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation. N Engl J Med 2017; 377: 523-533
• 29 Hartkopf AD, Brucker SY, Taran FA. et al. International pooled analysis of the prognostic impact of disseminated tumor cells from the bone marrow in early breast cancer: Results from the PADDY study. San Antonio Breast Cancer Symposium 2018; 2018: Abstract GS5-07
• 30 Hahnen E, Lederer B, Hauke J. et al. Germline Mutation Status, Pathological Complete Response, and Disease-Free Survival in Triple-Negative Breast Cancer: Secondary Analysis of the GeparSixto Randomized Clinical Trial. JAMA Oncol 2017; 3: 1378-1385
• 31 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.
• 32 Halsted WS. I. The Results of Operations for the Cure of Cancer of the Breast Performed at the Johns Hopkins Hospital from June, 1889, to January, 1894. Ann Surg 1894; 20: 497-555
• 33 Patey DH. A review of 146 cases of carcinoma of the breast operated on between 1930 and 1943. Br J Cancer 1967; 21: 260-269
• 34 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
• 35 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
• 36 van Roozendaal LM, Vane MLG, van Dalen T. et al. Clinically node negative breast cancer patients undergoing breast conserving therapy, sentinel lymph node procedure versus follow-up: a Dutch randomized controlled multicentre trial (BOOG 2013-08). BMC Cancer 2017; 17: 459
• 37 Reimer T, Stachs A, Nekljudova V. et al. Restricted Axillary Staging in Clinically and Sonographically Node-Negative Early Invasive Breast Cancer (c/iT1–2) in the Context of Breast Conserving Therapy: First Results Following Commencement of the Intergroup-Sentinel-Mamma (INSEMA) Trial. Geburtsh Frauenheilk 2017; 77: 149-157
• 38 Gentilini O, Veronesi U. Abandoning sentinel lymph node biopsy in early breast cancer? A new trial in progress at the European Institute of Oncology of Milan (SOUND: Sentinel node vs. Observation after axillary UltraSouND). Breast 2012; 21: 678-681
• 39 Donker M, van Tienhoven G, Straver ME. et al. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981-22023 AMAROS): a randomised, multicentre, open-label, phase 3 non-inferiority trial. Lancet Oncol 2014; 15: 1303-1310
• 40 Galimberti V, Cole BF, Zurrida S. et al. Axillary dissection versus no axillary dissection in patients with sentinel-node micrometastases (IBCSG 23-01): a phase 3 randomised controlled trial. Lancet Oncol 2013; 14: 297-305
• 41 Galimberti V, Cole BF, Viale G. et al. Axillary dissection versus no axillary dissection in patients with breast cancer and sentinel-node micrometastases (IBCSG 23-01): 10-year follow-up of a randomised, controlled phase 3 trial. Lancet Oncol 2018; 19: 1385-1393
• 42 Giuliano AE, Ballman KV, McCall L. et al. Effect of Axillary Dissection vs. No Axillary Dissection on 10-Year Overall Survival Among Women With Invasive Breast Cancer and Sentinel Node Metastasis: The ACOSOG Z0011 (Alliance) Randomized Clinical Trial. JAMA 2017; 318: 918-926
• 43 Giuliano AE, Ballman K, McCall L. et al. Locoregional Recurrence After Sentinel Lymph Node Dissection With or Without Axillary Dissection in Patients With Sentinel Lymph Node Metastases: Long-term Follow-up From the American College of Surgeons Oncology Group (Alliance) ACOSOG Z0011 Randomized Trial. Ann Surg 2016; 264: 413-420
• 44 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
• 45 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
• 46 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
• 47 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
• 48 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
• 49 Kurian AW, Bondarenko I, Jagsi R. et al. Recent Trends in Chemotherapy Use and Oncologistsʼ Treatment Recommendations for Early-Stage Breast Cancer. J Natl Cancer Inst 2018; 110: 493-500
• 50 Schmid P, Adams S, Rugo HS. et al. Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. N Engl J Med 2018; 379: 2108-2121
• 51 Loibl S, Untch M, Burchardi N. et al. Randomized phase II neoadjuvant study (GeparNuevo) to investigate the addition of durvalumab to a taxane-anthracycline containing chemotherapy in triple negative breast cancer (TNBC). J Clin Oncol 2018; 36(15_suppl: 104
• 52 Denkert C, von Minckwitz G, Darb-Esfahani S. et al. Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy. Lancet Oncol 2018; 19: 40-50
• 53 OʼLoughlin M, Andreu X, Bianchi S. et al. Reproducibility and predictive value of scoring stromal tumour infiltrating lymphocytes in triple-negative breast cancer: a multi-institutional study. Breast Cancer Res Treat 2018; 171: 1-9
• 54 Wurfel F, Erber R, Huebner H. et al. TILGen: A Program to Investigate Immune Targets in Breast Cancer Patients – First Results on the Influence of Tumor-Infiltrating Lymphocytes. Breast Care (Basel) 2018; 13: 8-14
• 55 Ali HR, Dariush A, Thomas J. et al. Lymphocyte density determined by computational pathology validated as a predictor of response to neoadjuvant chemotherapy in breast cancer: secondary analysis of the ARTemis trial. Ann Oncol 2017; 28: 1832-1835
• 56 Criscitiello C, Bagnardi V, Pruneri G. et al. Prognostic value of tumour-infiltrating lymphocytes in small HER2-positive breast cancer. Eur J Cancer 2017; 87: 164-171
• 57 Goldhirsch A, Glick JH, Gelber RD. et al. Meeting highlights: International Consensus Panel on the Treatment of Primary Breast Cancer. Seventh International Conference on Adjuvant Therapy of Primary Breast Cancer. J Clin Oncol 2001; 19: 3817-3827
• 58 Goldhirsch A, Wood WC, Gelber RD. et al. Meeting highlights: updated international expert consensus on the primary therapy of early breast cancer. J Clin Oncol 2003; 21: 3357-3365
• 59 Goldhirsch A, Glick JH, Gelber RD. et al. Meeting highlights: international expert consensus on the primary therapy of early breast cancer 2005. Ann Oncol 2005; 16: 1569-1583
• 60 Goldhirsch A, Wood WC, Gelber RD. et al. Progress and promise: highlights of the international expert consensus on the primary therapy of early breast cancer 2007. Ann Oncol 2007; 18: 1133-1144
• 61 Goldhirsch A, Ingle JN, Gelber RD. et al. Thresholds for therapies: highlights of the St Gallen International Expert Consensus on the primary therapy of early breast cancer 2009. Ann Oncol 2009; 20: 1319-1329
• 62 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
• 63 Goldhirsch A, Winer EP, Coates AS. et al. Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013. Ann Oncol 2013; 24: 2206-2223
• 64 Francis PA, Pagani O, Fleming GF. et al. Tailoring Adjuvant Endocrine Therapy for Premenopausal Breast Cancer. N Engl J Med 2018; 379: 122-137
• 65 Slamon D, Eiermann W, Robert N. et al. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med 2011; 365: 1273-1283
• 66 Konecny GE, Pauletti G, Untch M. et al. Association between HER2, TOP2A, and response to anthracycline-based preoperative chemotherapy in high-risk primary breast cancer. Breast Cancer Res Treat 2010; 120: 481-489
• 67 Press MF, Sauter G, Buyse M. et al. Alteration of topoisomerase II-alpha gene in human breast cancer: association with responsiveness to anthracycline-based chemotherapy. J Clin Oncol 2011; 29: 859-867
• 68 Fasching PA, Weihbrecht S, Haeberle L. et al. HER2 and TOP2A amplification in a hospital-based cohort of breast cancer patients: associations with patient and tumor characteristics. Breast Cancer Res Treat 2014; 145: 193-203
• 69 Janni W, Nitz U, Rack BK. et al. Pooled analysis of two randomized phase III trials (PlanB/SuccessC) comparing six cycles of docetaxel and cyclophosphamide to sequential anthracycline taxane chemotherapy in patients with intermediate and high risk HER2-negative early breast cancer (n = 5,923). J Clin Oncol 2018; 36: 52 doi:10.1200/JCO.2018.1236.1215_suppl.1522
• 70 Nitz U, Gluz O, Clemens M. et al. West German Study PlanB Trial: Adjuvant Four Cycles of Epirubicin and Cyclophosphamide Plus Docetaxel Versus Six Cycles of Docetaxel and Cyclophosphamide in HER2-Negative Early Breast Cancer. J Clin Oncol 2019; 37: 799-808
• 71 Mobus V. Adjuvant Dose-Dense Chemotherapy in Breast Cancer: Standard of Care in High-Risk Patients. Breast Care (Basel) 2016; 11: 8-12
• 72 Early Breast Cancer Trialistsʼ Collaborative Group (EBCTCG). Increasing the dose intensity of chemotherapy by more frequent administration or sequential scheduling: a patient-level meta-analysis of 37 298 women with early breast cancer in 26 randomised trials. Lancet 2019; 393: 1440-1452 doi:10.1016/S0140-6736(18)33137-4
• 73 Poggio F, Bruzzone M, Ceppi M. et al. Platinum-based neoadjuvant chemotherapy in triple-negative breast cancer: a systematic review and meta-analysis. Ann Oncol 2018; 29: 1497-1508
• 74 Early Breast Cancer Trialistsʼ Collaborative Group (EBCTCG). 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
• 75 Masuda N, Lee SJ, Ohtani S. et al. Adjuvant Capecitabine for Breast Cancer after Preoperative Chemotherapy. N Engl J Med 2017; 376: 2147-2159
• 76 von Minckwitz G, Huang CS, Mano MS. et al. Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer. N Engl J Med 2018; DOI: 10.1056/NEJMoa1814017.
• 77 von Minckwitz G, Bear H, Bonnefoi H. et al. Abstract OT2-6-11: PENELOPE: Phase III study evaluating palbociclib (PD-0332991), a cyclin-dependent kinase (CDK) 4/6 inhibitor in patients with hormone-receptor-positive, HER2-normal primary breast cancer with high relapse risk after neoadjuvant chemotherapy (GBG-78/BIG1-13). Cancer Res 2013; DOI: 10.1158/0008-5472.SABCS13-OT2-6-11.