Update Breast Cancer 2020 Part 3 – Early Breast Cancer

Jens Huober; Andreas Schneeweiss; Andreas D. Hartkopf; Volkmar Müller; Michael P. Lux; Wolfgang Janni; Johannes Ettl; Erik Belleville; Marc Thill; Peter A. Fasching; Hans-Christian Kolberg; Carla E. Schulmeyer; Manfred Welslau; Friedrich Overkamp; Hans Tesch; Tanja N. Fehm; Diana Lüftner; Florian Schütz; Achim Wöckel

doi:10.1055/a-1270-7208

Geburtshilfe und Frauenheilkunde, Table of Contents

CC BY-NC-ND 4.0 · Geburtshilfe Frauenheilkd 2020; 80(11): 1105-1114
DOI: 10.1055/a-1270-7208

GebFra Science

Review/Übersicht

Update Breast Cancer 2020 Part 3 – Early Breast Cancer

Article in several languages: English | deutsch

Jens Huober

¹Department of Gynecology and Obstetrics, Ulm University Hospital, Ulm, Germany

,

Andreas Schneeweiss

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

,

Andreas D. Hartkopf

³Department of Obstetrics and Gynecology, University of Tübingen, Tübingen, Germany

,

Volkmar Müller

⁴Department of Gynecology, Hamburg-Eppendorf University Medical Center, Hamburg, Germany

,

Michael P. Lux

⁵Klinik für Gynäkologie und Geburtshilfe, Frauenklinik St. Louise, Paderborn, St. Josefs-Krankenhaus, Salzkotten, Germany

,

Wolfgang Janni

¹Department of Gynecology and Obstetrics, Ulm University Hospital, Ulm, Germany

,

Johannes Ettl

⁶Department of Obstetrics and Gynecology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany

,

Erik Belleville

⁷ClinSol GmbH & Co KG, Würzburg, Germany

,

Marc Thill

⁸Agaplesion Markus Krankenhaus, Department of Gynecology and Gynecological Oncology, Frankfurt, Germany

,

Peter A. Fasching

⁹Erlangen University Hospital, Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany

,

Hans-Christian Kolberg

¹⁰Department of Gynecology and Obstetrics, Marienhospital Bottrop, Bottrop, Germany

,

Carla E. Schulmeyer

⁹Erlangen University Hospital, Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany

,

Manfred Welslau

¹¹Onkologie Aschaffenburg, Aschaffenburg, Germany

,

Friedrich Overkamp

¹²OncoConsult Overkamp, Berlin, Germany

,

Hans Tesch

¹³Oncology Practice at Bethanien Hospital Frankfurt, Frankfurt, Germany

,

Tanja N. Fehm

¹⁴Department of Gynecology and Obstetrics, University Hospital Düsseldorf, Düsseldorf, Germany

,

Diana Lüftner

¹⁵Charité University Hospital, Department of Hematology, Oncology and Tumour Immunology, Berlin, Germany

,

Florian Schütz

¹⁶Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany

,

Achim Wöckel

¹⁷Department of Gynecology and Obstetrics, University Hospital Würzburg, Würzburg, Germany

› Author Affiliations

Abstract

The treatment of patients with early breast cancer has always been characterised by escalation by new therapies and de-escalation through identification of better treatment regimens or introduction of better tools to estimate prognosis. Efforts in some of these areas in the last few years have led to solid data. The results of the large studies of de-escalation through use of multi-gene tests are available, as are the results of some studies that investigated the new anti-HER2 substances T-DM1 and pertuzumab in the early treatment situation. Several large-scale studies examining the role of CDK4/6 inhibitors will soon be concluded so innovations can be anticipated in this area also. This review article will summarise and classify the results of the latest publications.

Key words

early breast cancer - prevention - treatment - prognosis - immunotherapy - digital medicine

Full Text

References

References/Literatur
1 Ditsch N, Untch M, Thill M. et al. AGO Recommendations for the Diagnosis and Treatment of Patients with Early Breast Cancer: Update 2019. Breast Care (Basel) 2019; 14: 224-245
2 Thill M, Jackisch C, Janni W. et al. AGO Recommendations for the Diagnosis and Treatment of Patients with Locally Advanced and Metastatic Breast Cancer: Update 2019. Breast Care (Basel) 2019; 14: 247-255
3 Welslau M, Hartkopf AD, Muller V. et al. Update Breast Cancer 2019 Part 5 – Diagnostic and Therapeutic Challenges of New, Personalised Therapies in Patients with Advanced Breast Cancer. Geburtshilfe Frauenheilkd 2019; 79: 1090-1099
4 Schutz F, Fasching PA, Welslau M. et al. Update Breast Cancer 2019 Part 4 – Diagnostic and Therapeutic Challenges of New, Personalised Therapies for Patients with Early Breast Cancer. Geburtshilfe Frauenheilkd 2019; 79: 1079-1089
5 Kolberg HC, Schneeweiss A, Fehm TN. et al. Update Breast Cancer 2019 Part 3 – Current Developments in Early Breast Cancer: Review and Critical Assessment by an International Expert Panel. Geburtshilfe Frauenheilkd 2019; 79: 470-482
6 Wunderle M, Olmes G, Nabieva N. et al. Risk, Prediction and Prevention of Hereditary Breast Cancer – Large-Scale Genomic Studies in Times of Big and Smart Data. Geburtshilfe Frauenheilkd 2018; 78: 481-492
7 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;
8 Couch FJ, Shimelis H, Hu C. et al. Associations Between Cancer Predisposition Testing Panel Genes and Breast Cancer. JAMA Oncol 2017; 3: 1190-1196
9 Fachal L, Aschard H, Beesley J. et al. Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes. Nat Genet 2020;
10 Wu L, Shi W, Long J. et al. A transcriptome-wide association study of 229,000 women identifies new candidate susceptibility genes for breast cancer. Nat Genet 2018;
11 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
12 Michailidou K, Lindstrom S, Dennis J. et al. Association analysis identifies 65 new breast cancer risk loci. Nature 2017; 551: 92-94
13 Day FR, Thompson DJ, Helgason H. et al. Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk. Nat Genet 2017; 49: 834-841
14 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
15 Day FR, Ruth KS, Thompson DJ. et al. Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair. Nat Genet 2015; 47: 1294-1303
16 Pharoah PD, Tsai YY, Ramus SJ. et al. GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer. Nat Genet 2013; 45: 362-370 370e1–370e2
17 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
18 Garcia-Closas M, Couch FJ, Lindstrom S. et al. Genome-wide association studies identify four ER negative-specific breast cancer risk loci. Nat Genet 2013; 45: 392-398 398e1–398e2
19 Bojesen SE, Pooley KA, Johnatty SE. et al. Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer. Nat Genet 2013; 45: 371-384 384e1–384e2
20 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
21 Haiman CA, Chen GK, Vachon CM. et al. A common variant at the TERT-CLPTM1 L locus is associated with estrogen receptor-negative breast cancer. Nat Genet 2011; 43: 1210-1214
22 Antoniou AC, Wang X, Fredericksen ZS. et al. A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population. Nat Genet 2010; 42: 885-892
23 Ghoussaini M, French JD, Michailidou K. et al. Evidence that the 5p12 Variant rs10941679 Confers Susceptibility to Estrogen-Receptor-Positive Breast Cancer through FGF10 and MRPS30 Regulation. Am J Hum Genet 2016; 99: 903-911
24 Couch FJ, Kuchenbaecker KB, Michailidou K. et al. Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer. Nat Commun 2016; 7: 11375
25 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
26 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
27 Boyd NF, Guo H, Martin LJ. et al. Mammographic density and the risk and detection of breast cancer. N Engl J Med 2007; 356: 227-236
28 Heusinger K, Loehberg CR, Haeberle L. et al. Mammographic density as a risk factor for breast cancer in a German case-control study. Eur J Cancer Prev 2011; 20: 1-8
29 Heusinger K, Jud SM, Haberle L. et al. Association of mammographic density with the proliferation marker Ki-67 in a cohort of patients with invasive breast cancer. Breast Cancer Res Treat 2012; 135: 885-892
30 Heusinger K, Jud SM, Haberle L. et al. Association of mammographic density with hormone receptors in invasive breast cancers: results from a case-only study. Int J Cancer 2012; 131: 2643-2649
31 Bayer CM, Beckmann MW, Fasching PA. Updates on the role of receptor activator of nuclear factor kappaB/receptor activator of nuclear factor kappaB ligand/osteoprotegerin pathway in breast cancer risk and treatment. Curr Opin Obstet Gynecol 2017; 29: 4-11
32 Hack CC, Stoll MJ, Jud SM. et al. Correlation of mammographic density and serum calcium levels in patients with primary breast cancer. Cancer Med 2017; 6: 1473-1481
33 Rudolph A, Fasching PA, Behrens S. et al. A comprehensive evaluation of interaction between genetic variants and use of menopausal hormone therapy on mammographic density. Breast Cancer Res 2015; 17: 110
34 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: dju397
35 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
36 Vachon CM, Scott CG, Tamimi RM. et al. Joint association of mammographic density adjusted for age and body mass index and polygenic risk score with breast cancer risk. Breast Cancer Res 2019; 21: 68
37 Britt KL, Cuzick J, Phillips KA. Key steps for effective breast cancer prevention. Nat Rev Cancer 2020;
38 Kapoor PM, Mavaddat N, Choudhury PP. et al. Combined associations of a polygenic risk score and classical risk factors with breast cancer risk. J Natl Cancer Inst 2020;
39 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;
40 Mavaddat N, Pharoah PDP, Michailidou K. et al. Prediction of breast cancer risk based on profiling with common genetic variants. J Natl Cancer Inst 2015; 107: djv036
41 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
42 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
43 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
44 Cortes J, Gebhart G, Borrego MR. et al. Chemotherapy (CT) de-escalation using an FDG-PET/CT (F-PET) and pathological response-adapted strategy in HER2[+] early breast cancer (EBC): PHERGain Trial. J Clin Oncol 2020; 38: 503-503
45 Fasching PA, Hartkopf AD, Gass P. et al. Efficacy of neoadjuvant pertuzumab in addition to chemotherapy and trastuzumab in routine clinical treatment of patients with primary breast cancer: a multicentric analysis. Breast Cancer Res Treat 2018;
46 Slamon D, Eiermann W, Robert N. et al. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med 2011; 365: 1273-1283
47 Slamon DJ, Eiermann W, Robert NJ. et al. Ten year follow-up of BCIRG-006 comparing doxorubicin plus cyclophosphamide followed by docetaxel (AC -> T) with doxorubicin plus cyclophosphamide followed by docetaxel and trastuzumab (AC -> TH) with docetaxel, carboplatin and trastuzumab (TCH) in HER2+early breast cancer. Cancer Res 2016;
48 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
49 van Ramshorst MS, van der Voort A, van Werkhoven ED. et al. Neoadjuvant chemotherapy with or without anthracyclines in the presence of dual HER2 blockade for HER2-positive breast cancer (TRAIN-2): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol 2018; 19: 1630-1640
50 van der Voort A, van Ramshorst MS, van Werkhoven E. et al. Three-year follow-up of neoadjuvant chemotherapy with or without anthracyclines in the presence of dual HER2-blockade for HER2-positive breast cancer (TRAIN-2): A randomized phase III trial. J Clin Oncol 2020; 38: 501-501
51 Fasching PA, Jud SM, Hauschild M. et al. FemZone trial: a randomized phase II trial comparing neoadjuvant letrozole and zoledronic acid with letrozole in primary breast cancer patients. BMC Cancer 2014; 14: 66
52 Fasching PA, Abad MF, Garcia-Saenz JA. et al. Biological and clinical effects of abemaciclib in a phase 2 neoadjuvant study for postmenopausal patients with HR+/HER2-breast cancer. Oncol Res Treat 2017; 40: 225-226
53 Mayer IA, Prat A, Egle D. et al. A Phase II Randomized Study of Neoadjuvant Letrozole Plus Alpelisib for Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer (NEO-ORB). Clin Cancer Res 2019; 25: 2975-2987
54 Hurvitz SA, Martin M, Press MF. et al. Potent Cell-Cycle Inhibition and Upregulation of Immune Response with Abemaciclib and Anastrozole in neoMONARCH, Phase II Neoadjuvant Study in HR(+)/HER2(−) Breast Cancer. Clin Cancer Res 2020; 26: 566-580
55 Khan QJ, OʼDea A, Bardia A. et al. Letrozole + ribociclib versus letrozole + placebo as neoadjuvant therapy for ER+ breast cancer (FELINE trial). J Clin Oncol 2020; 38: 505-505
56 Ellis MJ, Tao Y, Luo J. et al. Outcome prediction for estrogen receptor-positive breast cancer based on postneoadjuvant endocrine therapy tumor characteristics. J Natl Cancer Inst 2008; 100: 1380-1388
57 Khan SA, Zhao F, Solin LJ. et al. A randomized phase III trial of systemic therapy plus early local therapy versus systemic therapy alone in women with de novo stage IV breast cancer: A trial of the ECOG-ACRIN Research Group (E2108). J Clin Oncol 2020; 38: LBA2
58 Soran A, Ozmen V, Ozbas S. et al. Randomized Trial Comparing Resection of Primary Tumor with No Surgery in Stage IV Breast Cancer at Presentation: Protocol MF07-01. Ann Surg Oncol 2018; 25: 3141-3149
59 Badwe R, Hawaldar R, Nair N. et al. Locoregional treatment versus no treatment of the primary tumour in metastatic breast cancer: an open-label randomised controlled trial. Lancet Oncol 2015; 16: 1380-1388
60 Verma S, Miles D, Gianni L. et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med 2012; 367: 1783-1791
61 von Minckwitz G, Huang CS, Mano MS. et al. Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer. N Engl J Med 2019; 380: 617-628
62 Hurvitz SA, Martin M, Symmans WF. et al. Neoadjuvant trastuzumab, pertuzumab, and chemotherapy versus trastuzumab emtansine plus pertuzumab in patients with HER2-positive breast cancer (KRISTINE): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol 2018; 19: 115-126
63 Hurvitz SA, Martin M, Jung KH. et al. Neoadjuvant Trastuzumab Emtansine and Pertuzumab in Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: Three-Year Outcomes From the Phase III KRISTINE Study. J Clin Oncol 2019; 37: 2206-2216 doi:10.1200/JCO.19.00882
64 Harbeck N, Im S-A, Barrios CH. et al. Primary analysis of KAITLIN: A phase III study of trastuzumab emtansine (T-DM1) + pertuzumab versus trastuzumab + pertuzumab + taxane, after anthracyclines as adjuvant therapy for high-risk HER2-positive early breast cancer (EBC). J Clin Oncol 2020; 38: 500-500
65 Sparano JA, Gray RJ, Makower DF. et al. Prospective Validation of a 21-Gene Expression Assay in Breast Cancer. N Engl J Med 2015; 373: 2005-2014
66 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
67 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
68 Cardoso F, vanʼt Veer L, Poncet C. et al. MINDACT: Long-term results of the large prospective trial testing the 70-gene signature MammaPrint as guidance for adjuvant chemotherapy in breast cancer patients. J Clin Oncol 2020; 38: 506-506
69 Denkert C, Lambertini C, Fasching PA. et al. Biomarker data from KATHERINE: A phase III study of adjuvant trastuzumab emtansine (T-DM1) versus trastuzumab (H) in patients with residual invasive disease after neoadjuvant therapy for HER2-positive breast cancer. J Clin Oncol 2020; 38: 502-502
70 Bardia A, Mayer IA, Vahdat LT. et al. Sacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer. N Engl J Med 2019; 380: 741-751
71 Marme F. Phase-III-Studie zur postneoadjuvanten Behandlung mit dem Antikörper-Medikamenten-Konjugat Sacituzumab-Govitecan bei Frauen mit frühem, HER2-negativem Brustkrebs und hohem Rückfallrisiko nach einer Standardbehandlung im neoadjuvantenSetting – SASCIA. 2020 Online (Stand: 16.07.2020): https://www.gbg.de/wAssets/docs/events-vortraege/2020_JT/23_SASCIA.pdf