Update Breast Cancer 2019 Part 3 – Current Developments in Early Breast Cancer: Review and Critical Assessment by an International Expert Panel

Hans-Christian Kolberg; Andreas Schneeweiss; Tanja N. Fehm; Achim Wöckel; Jens Huober; Constanza Pontones; Adriana Titzmann; Erik Belleville; Michael P. Lux; Wolfgang Janni; Andreas D. Hartkopf; Florin-Andrei Taran; Markus Wallwiener; Friedrich Overkamp; Hans Tesch; Johannes Ettl; Diana Lüftner; Volkmar Müller; Florian Schütz; Peter A. Fasching; Sara Y. Brucker

doi:10.1055/a-0887-0861

Geburtshilfe und Frauenheilkunde, Table of Contents

CC BY-NC-ND 4.0 · Geburtshilfe Frauenheilkd 2019; 79(05): 470-482
DOI: 10.1055/a-0887-0861

GebFra Science

Review/Übersicht

Georg Thieme Verlag KG Stuttgart · New York

Update Breast Cancer 2019 Part 3 – Current Developments in Early Breast Cancer: Review and Critical Assessment by an International Expert Panel

Article in several languages: English | deutsch

Hans-Christian Kolberg

¹Department of Gynecology and Obstetrics, Marienhospital Bottrop, Bottrop, Germany

,

Andreas Schneeweiss

²National Center for Tumor Diseases, Division Gynecologic Oncology, University Hospital and German Cancer Research Center Heidelberg, Heidelberg, Germany

,

Tanja N. Fehm

³Department of Gynecology and Obstetrics, University Hospital Düsseldorf, Düsseldorf, Germany

,

Achim Wöckel

⁴Department of Gynecology and Obstetrics, University Hospital Würzburg, Würzburg, Germany

,

Jens Huober

⁵Department of Gynecology and Obstetrics, Ulm University Hospital, Ulm, Germany

,

Constanza Pontones

⁶Erlangen University Hospital, Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany

,

Adriana Titzmann

⁶Erlangen University Hospital, Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany

,

Erik Belleville

⁷ClinSol GmbH & Co KG, Würzburg, Germany

,

Michael P. Lux

⁸Kooperatives Brustzentrum Paderborn, Klinik für Gynäkologie und Geburtshilfe, Frauenklinik St. Louise, Paderborn, St. Josefs-Krankenhaus, Salzkotten, Germany

,

Wolfgang Janni

⁵Department of Gynecology and Obstetrics, Ulm University Hospital, Ulm, Germany

,

Andreas D. Hartkopf

⁹Department of Obstetrics and Gynecology, University of Tübingen, Tübingen, Germany

,

Florin-Andrei Taran

⁹Department of Obstetrics and Gynecology, University of Tübingen, Tübingen, Germany

,

Markus Wallwiener

¹⁰Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany

,

Friedrich Overkamp

¹¹OncoConsult Hamburg GmbH, Hamburg, Germany

,

Hans Tesch

¹²Oncology Practice at Bethanien Hospital Frankfurt, Frankfurt, Germany

,

Johannes Ettl

¹³Department of Obstetrics and Gynecology, Technical University of Munich, School of Medicine, Klinikum rechts der Isar, Munich, Germany

,

Diana Lüftner

¹⁴Charité University Hospital, Campus Benjamin Franklin, Department of Hematology, Oncology and Tumour Immunology, Berlin, Germany

,

Volkmar Müller

¹⁵Department of Gynecology, Hamburg-Eppendorf University Medical Center, Hamburg, Germany

,

Florian Schütz

¹⁰Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany

,

Peter A. Fasching

⁶Erlangen University Hospital, Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany

,

Sara Y. Brucker

⁹Department of Obstetrics and Gynecology, University of Tübingen, Tübingen, Germany

› Author Affiliations

Abstract

The treatment of breast cancer patients in a curative situation is special in many ways. The local therapy with surgery and radiation therapy is a central aspect of the treatment. The complete elimination of tumour cells at the site of the primary disease must be ensured while simultaneously striving to keep the long-term effects as minor as possible. There is still focus on the continued reduction of the invasiveness of local therapy. With regard to systemic therapy, chemotherapies with taxanes, anthracyclines and, in some cases, platinum-based chemotherapies have become established in the past couple of decades. The context for use is being continually further defined. Likewise, there are questions in the case of antihormonal therapy which also still need to be further defined following the introduction of aromatase inhibitors, such as the length of therapy or ovarian suppression in premenopausal patients. Finally, personalisation of the treatment of early breast cancer patients is also being increasingly used. Prognostic tests could potentially support therapeutic decisions. It must also be considered how the possible use of new therapies, such as checkpoint inhibitors and CDK4/6 inhibitors could look in practice once study results in this regard are available. This overview addresses the backgrounds on the current votes taken by the international St. Gallen panel of experts in Vienna in 2019 for current questions in the treatment of breast cancer patients in a curative situation.

Key words

early breast cancer - adjuvant therapy - neoadjuvant therapy - St. Gallen panel of experts

Full Text

References

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;
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;
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;
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;
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;
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;

Supplementary Material

Supporting Information