Update Mammakarzinom 2022 Teil 1 – Brustkrebs in frühen Krankheitsstadien

Manfred Welslau; Volkmar Müller; Diana Lüftner; Florian Schütz; Elmar Stickeler; Peter A. Fasching; Wolfgang Janni; Christoph Thomssen; Isabell Witzel; Tanja N. Fehm; Erik Belleville; Simon Bader; Katharina Seitz; Michael Untch; Marc Thill; Hans Tesch; Nina Ditsch; Michael P. Lux; Bahriye Aktas; Maggie Banys-Paluchowski; Andreas Schneeweiss; Nadia Harbeck; Rachel Würstlein; Andreas D. Hartkopf; Achim Wöckel; Barbara Seliger; Chiara Massa; Hans Christian Kolberg

doi:10.1055/a-1898-4367

Senologie - Zeitschrift für Mammadiagnostik und -therapie, Table of Contents

Senologie - Zeitschrift für Mammadiagnostik und -therapie 2022; 19(03): 281-291
DOI: 10.1055/a-1898-4367

Übersicht

Update Mammakarzinom 2022 Teil 1 – Brustkrebs in frühen Krankheitsstadien

Update Breast Cancer 2022 Part 1 – Early Stage Breast Cancer

Manfred Welslau

¹Onkologie Aschaffenburg, Aschaffenburg

,

Volkmar Müller

²Department of Gynecology, Hamburg-Eppendorf University Medical Center, Hamburg

,

Diana Lüftner

³Charité University Hospital, Department of Hematology, Oncology and Tumour Immunology, University Medicine Berlin, Berlin

,

Florian Schütz

⁴Gynäkologie und Geburtshilfe, Diakonissen-Stiftungs-Krankenhaus Speyer, Speyer

,

Elmar Stickeler

⁵Department of Gynecology and Obstetrics, RWTH University Hospital Aachen, Aachen

,

Peter A. Fasching

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

,

Wolfgang Janni

⁷Department of Gynecology and Obstetrics, Ulm University Hospital, Ulm

,

Christoph Thomssen

⁸Department of Gynaecology, Martin-Luther-University Halle-Wittenberg, Halle (Saale)

,

Isabell Witzel

²Department of Gynecology, Hamburg-Eppendorf University Medical Center, Hamburg

,

Tanja N. Fehm

⁹Department of Gynecology and Obstetrics, University Hospital Düsseldorf, Düsseldorf

,

Erik Belleville

¹⁰ClinSol GmbH & Co KG, Würzburg

,

Simon Bader

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

,

Katharina Seitz

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

,

Michael Untch

¹¹Clinic for Gynecology and Obstetrics, Breast Cancer Center, Genecologic Oncology Center, Helios Klinikum Berlin Buch, Berlin

,

Marc Thill

¹²Agaplesion Markus Krankenhaus, Department of Gynecology and Gynecological Oncology, Frankfurt am Main

,

Hans Tesch

¹³Oncology Practice at Bethanien Hospital, Frankfurt am Main

,

Nina Ditsch

¹⁴Department of Gynecology and Obstetrics, University Hospital Augsburg, Augsburg

,

Michael P. Lux

¹⁵Klinik für Gynäkologie und Geburtshilfe, Frauenklinik St. Louise, Paderborn, St. Josefs-Krankenhaus, Salzkotten, St. Vincenz Krankenhaus GmbH

,

Bahriye Aktas

¹⁶Klinik und Poliklinik für Gynäkologie, Universitätsklinikum Leipzig, Leipzig

,

Maggie Banys-Paluchowski

¹⁷Department of Gynecology and Obstetrics, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck

,

Andreas Schneeweiss

¹⁸National Center for Tumor Diseases (NCT), Heidelberg University Hospital and German Cancer Research Center, Heidelberg

,

Nadia Harbeck

¹⁹Breast Center, Department of Gynecology and Obstetrics and CCC Munich LMU, LMU University Hospital, Munich

,

Rachel Würstlein

¹⁹Breast Center, Department of Gynecology and Obstetrics and CCC Munich LMU, LMU University Hospital, Munich

,

Andreas D. Hartkopf

⁷Department of Gynecology and Obstetrics, Ulm University Hospital, Ulm

,

Achim Wöckel

²⁰Department of Gynecology and Obstetrics, University Hospital Würzburg, Würzburg

,

Barbara Seliger

²¹Martin-Luther-Universitat Halle-Wittenberg, Institute of Medical Immunology, Halle (Saale)

,

Chiara Massa

²¹Martin-Luther-Universitat Halle-Wittenberg, Institute of Medical Immunology, Halle (Saale)

,

Hans Christian Kolberg

²²Department of Gynecology and Obstetrics, Marienhospital Bottrop, Bottrop

› Author Affiliations

Abstract

Zusammenfassung

Die Erkenntnisse über die Behandlung von Mammakarzinompatientinnen mit frühen Krankheitsstadien haben im letzten Jahr deutlich zugenommen. Abemaciclib, Olaparib und Pembrolizumab sind neue Medikamente mit einer guten Wirksamkeit bei den entsprechenden Patientinnengruppen. Jedoch sind einige Fragestellungen nach wie vor unbeantwortet. Insbesondere welchen Patientinnen unnötige Therapien erspart werden können, ist bei prämenopausalen Patientinnen mit einem hormonrezeptorpositiven Mammakarzinom weiterhin unklar. Die Frage, inwieweit eine Chemotherapie einen direkten zytotoxischen Effekt auf den Tumor hat oder eher dadurch wirkt, dass die Ovarfunktion durch die Chemotherapie reduziert wird, könnte wegweisend sein. Dieser Patientinnengruppe kann möglicherweise eine Chemotherapie erspart bleiben. Neue, bislang experimentelle Biomarker-Analysemethoden, wie die räumliche Analyse der Genexpression (spatial transcriptomics), halten nach und nach Einzug in die großen randomisierten Phase-III-Studien, wie die NeoTRIPStudie. Dies führt wiederum zum besseren Verständnis der prädiktiven Faktoren neuer Therapien, zum Beispiel der Immuntherapie. Diese Übersichtsarbeit fasst die wissenschaftlichen Neuerungen der aktuellen Kongresse wie dem San Antonio Breast Cancer Symposium 2021, aber auch von kürzlich veröffentlichten Publikationen zusammen.

Abstract

Evidence relating to the treatment of breast cancer patients with early-stage disease has increased significantly in the past year. Abemaciclib, olaparib, and pembrolizumab are new drugs with good efficacy in the relevant patient groups. However, some questions remain unanswered. In particular, it remains unclear which premenopausal patients with hormone receptor-positive breast cancer should be spared unnecessary treatment. The question of the degree to which chemotherapy exerts a direct cytotoxic effect on the tumor or reduces ovarian function through chemotherapy could be of key importance. This group of patients could potentially be spared chemotherapy. New, previously experimental biomarker analysis methods, such as spatial analysis of gene expression (spatial transcriptomics) are gradually finding their way into large randomized phase III trials, such as the NeoTRIP trial. This in turn leads to a better understanding of the predictive factors of new therapies, for example immunotherapy. This review summarizes the scientific innovations from recent congresses such as the San Antonio Breast Cancer Symposium 2021 but also from recent publications.

Schlüsselwörter

BRCA (Brustkrebs‑Antigen) - Brustkrebs - Östrogenrezeptor - orale Therapie

Key words

BRCA (breast cancer antigen) - breast cancer - estrogen receptor - oral therapy

Full Text

References

Literatur
1 Tutt ANJ, Garber JE, Kaufman B. et al. Adjuvant Olaparib for Patients with BRCA1- or BRCA2-Mutated Breast Cancer. N Engl J Med 2021; 384: 2394-2405
2 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
3 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
4 Turner NC, Telli ML, Rugo HS. et al. A Phase II Study of Talazoparib after Platinum or Cytotoxic Nonplatinum Regimens in Patients with Advanced Breast Cancer and Germline BRCA1/2 Mutations (ABRAZO). Clin Cancer Res 2019; 25: 2717-2724
5 Tutt ANJ, Garber J, Gelber RD. et al Pre-specified event driven analysis of Overall Survival (OS) in the OlympiA phase III trial of adjuvant olaparib (OL) in germline BRCA1/2 mutation (gBRCAm) associated breast cancer. Ann Oncol 2022;. ESMO Virtual Plenary VP1-2022
6 Ditsch N, Kolberg-Liedtke C, Friedrich M. et al. AGO Recommendations for the Diagnosis and Treatment of Patients with Early Breast Cancer: Update 2021. Breast Care (Basel) 2021; 16: 214-227
7 Ditsch N, Untch M, Kolberg-Liedtke C. et al. AGO Recommendations for the Diagnosis and Treatment of Patients with Locally Advanced and Metastatic Breast Cancer: Update 2020. Breast Care (Basel) 2020; 15: 294-309
8 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
9 Fasching PA, Yadav S, Hu C. et al. Mutations in BRCA1/2 and Other Panel Genes in Patients With Metastatic Breast Cancer-Association With Patient and Disease Characteristics and Effect on Prognosis. J Clin Oncol 2021; 39: 1619-1630
10 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
11 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;
12 Foulkes WD. The ten genes for breast (and ovarian) cancer susceptibility. Nat Rev Clin Oncol 2021; 18: 259-260
13 Müller V, Welslau M, Lüftner D. et al. Update Breast Cancer 2022 Part 2 – Advanced Stage Breast Cancer. Geburtshilfe Frauenheilkd 2022; 82: 590-600
14 Kraus C, Hoyer J, Vasileiou G. et al. Gene panel sequencing in familial breast/ovarian cancer patients identifies multiple novel mutations also in genes others than BRCA1/2. Int J Cancer 2017; 140: 95-102
15 Tung NM, Robson ME, Ventz S. et al. TBCRC048: Phase II Study of Olaparib for Metastatic Breast Cancer and Mutations in Homologous Recombination-Related Genes. J Clin Oncol 2020; 38: 4274-4282
16 Kar SP, Beesley J, Amin Al Olama A. et al. Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types. Cancer Discov 2016; 6: 1052-1067
17 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
18 Schmidt MK, Hogervorst F, van Hien R. et al. Age- and Tumor Subtype-Specific Breast Cancer Risk Estimates for CHEK2*1100delC Carriers. J Clin Oncol 2016; 34: 2750-2760
19 Dorling L, Carvalho S. Breast Cancer Association Consortium. et al. Breast Cancer Risk Genes – Association Analysis in More than 113000 Women. N Engl J Med 2021;
20 Dunning AM, Michailidou K, Kuchenbaecker KB. et al. Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170. Nat Genet 2016; 48: 374-386
21 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;
22 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
23 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
24 Chlebowski RT, Aragaki AK, Pan K. Breast Cancer Prevention: Time for Change. JCO Oncol Pract 2021; 17: 709-716
25 Nangia JR, Rimawi MF. Breast Cancer Prevention: Where Are We?. JCO Oncol Pract 2021; 17: 720-722
26 Chlebowski RT, Anderson GL, Aragaki AK. et al. Association of Menopausal Hormone Therapy With Breast Cancer Incidence and Mortality During Long-term Follow-up of the Womenʼs Health Initiative Randomized Clinical Trials. JAMA 2020; 324: 369-380
27 Rossouw JE, Anderson GL, Prentice RL. et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Womenʼs Health Initiative randomized controlled trial. JAMA 2002; 288: 321-333
28 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
29 Ingold Heppner B, Untch M, Denkert C. et al. Tumor-Infiltrating Lymphocytes: A Predictive and Prognostic Biomarker in Neoadjuvant-Treated HER2-Positive Breast Cancer. Clin Cancer Res 2016; 22: 5747-5754
30 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
31 Hollingsworth RE, Jansen K. Turning the corner on therapeutic cancer vaccines. NPJ Vaccines 2019; 4: 7
32 Antonarelli G, Corti C, Tarantino P. et al. Therapeutic cancer vaccines revamping: technology advancements and pitfalls. Ann Oncol 2021; 32: 1537-1551
33 Corti C, Giachetti P, Eggermont AMM. et al. Therapeutic vaccines for breast cancer: Has the time finally come?. Eur J Cancer 2022; 160: 150-174
34 Van Hoecke L, Verbeke R, Dewitte H. et al. mRNA in cancer immunotherapy: beyond a source of antigen. Mol Cancer 2021; 20: 48
35 Hashimoto S, Noguchi E, Bando H. et al. Neoantigen prediction in human breast cancer using RNA sequencing data. Cancer Sci 2021; 112: 465-475
36 Li W, Amei A, Bui F. et al. Impact of Neoantigen Expression and T-Cell Activation on Breast Cancer Survival. Cancers (Basel) 2021;
37 Reimann H, Nguyen A, Sanborn JZ. et al. Identification and validation of expressed HLA-binding breast cancer neoepitopes for potential use in individualized cancer therapy. J Immunother Cancer 2021;
38 Gerber B, Heintze K, Stubert J. et al. Axillary lymph node dissection in early-stage invasive breast cancer: is it still standard today?. Breast Cancer Res Treat 2011; 128: 613-624
39 Mittendorf EA, Bellon JR, King TA. Regional Nodal Management in Patients With Clinically Node-Negative Breast Cancer Undergoing Upfront Surgery. J Clin Oncol 2020; 38: 2273-2280
40 Bradley R, Braybrooke J, Gray R. et al Aromatase inhibitors versus tamoxifen in pre-menopausal women with estrogen receptor positive early stage breast cancer treated with ovarian suppression: A patient level meta-analysis of 7,030 women in four randomised trials. San Antonio Breast Cancer Symposium 2021;. 2021. GS2-04
41 Regan MM, Walley BA, Fleming GF. et al Randomized comparison of adjuvant aromatase inhibitor exemestane (E) plus ovarian function suppression (OFS) vs. tamoxifen (T) plus OFS in premenopausal women with hormone receptor-positive (HR+) early breast cancer (BC): update of the combined TEXT and SOFT trials. San Antonio Breast Cancer Symposium 2021;. 2021. GS2-05
42 Kalinsky K, Barlow WE, Gralow JR. et al. 21-Gene Assay to Inform Chemotherapy Benefit in Node-Positive Breast Cancer. N Engl J Med 2021; 385: 2336-2347
43 Piccart M, vanʼt Veer LJ, Poncet C. et al. 70-gene signature as an aid for treatment decisions in early breast cancer: updated results of the phase 3 randomised MINDACT trial with an exploratory analysis by age. Lancet Oncol 2021; 22: 476-488
44 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
45 Nitz UA, Gluz O, Kümmel S. et al Endocrine therapy response and 21- Gene Expression Assay for therapy guidance in HR+/HER2- early breast cancer. J Clin Oncol 2022;. in press
46 Ruddy KJ, Schaid DJ, Partridge AH. et al. Genetic predictors of chemotherapy-related amenorrhea in women with breast cancer. Fertil Steril 2019; 112: 731-739.e1
47 Kalinsky KM, Barlow WE, Gralow JR. et al Distant-disease free interval in participants (pts) with 1-3 positive lymph nodes (LN), hormone receptor-positive (HR+) and her2-negative (HER2-) breast cancer (BC) with recurrence score (RS) < or = 25 randomized to endocrine therapy (ET) ± chemotherapy (CT): SWOG s1007 (RxPONDER). San Antonio Breast Cancer Symposium 2021;. 2021. GS2-07
48 Mayer EL, Dueck AC, Martin M. et al. Palbociclib with adjuvant endocrine therapy in early breast cancer (PALLAS): interim analysis of a multicentre, open-label, randomised, phase 3 study. Lancet Oncol 2021; 22: 212-222
49 Gnant M, Dueck AC, Frantal S. et al. Adjuvant Palbociclib for Early Breast Cancer: The PALLAS Trial Results (ABCSG‑42/AFT‑05/BIG‑14-03). J Clin Oncol 2022; 40: 282-293
50 Harbeck N, Rastogi P, Martin M. et al. Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: updated efficacy and Ki-67 analysis from the monarchE study. Ann Oncol 2021; 32: 1571-1581
51 Precisiononcologynews.com. Novartis Anticipating Radioligands, New Precision Therapies to Continue Oncology Segment Growth. 2022 Online (Stand: 02.02.2022): https://www.precisiononcologynews.com/cancer/novartis-anticipating-radioligands-new-precision-therapiescontinue-oncology-segment-growth#Yf6ALvgxkuU
52 European Medicines Agency. Verzenios. 2022 Online (Stand: 19.05.2022): https://www.ema.europa.eu/en/documents/productinformation/verzenios-epar-product-information_en.pdf
53 Rugo HS, OʼShaughnessy J, Boyle F. et al. Adjuvant Abemaciclib Combined with Endocrine Therapy for High Risk Early Breast Cancer: Safety and Patient-Reported Outcomes From the monarchE Study. Ann Oncol 2022;
54 Nabieva N, Kellner S, Fehm T. et al. Influence of patient and tumor characteristics on early therapy persistence with letrozole in postmenopausal women with early breast cancer: results of the prospective Evaluate-TM study with 3941 patients. Ann Oncol 2018; 29: 186-192
55 Lüftner D, Schütz F, Stickeler E. et al. Update Breast Cancer 2021 Part 5 – Advanced Breast Cancer. Geburtshilfe Frauenheilkd 2022;
56 Thomssen C, Fehm TN, Stickeler E. et al. Update Breast Cancer 2021 Part 4 – Prevention and Early Stages. Geburtshilfe Frauenheilkd 2022;
57 Ruiz-Borrego M, Guerrero-Zotano A, Bermejo B. et al. Phase III evaluating the addition of fulvestrant (F) to anastrozole (A) as adjuvant therapy in postmenopausal women with hormone receptor-positive HER2-negative (HR+/HER2-) early breast cancer (EBC): results from the GEICAM/2006-10 study. Breast Cancer Res Treat 2019; 177: 115-125
58 Hurvitz SA, Quiroga V, Park YH. et al Neoadjuvant giredestrant (GDC-9545) + palbociclib versus anastrozole + palbociclib in postmenopausal women with estrogen receptor-positive, HER2-negative, untreated early breast cancer: Primary analysis of the randomized, open-label, phase II coopERA breast cancer study. San Antonio Breast Cancer Symposium 2021;. 2021. GS1-07
59 Bardia A, Neven P, Streich G. et al Elacestrant, an oral selective estrogen receptor degrader (SERD), vs. investigatorʼs choice of endocrine monotherapy for ER+/HER2-advanced/metastatic breast cancer (mBC) following progression on prior endocrine and CDK4/6 inhibitor therapy: Results of EMERALD phase 3 trial. San Antonio Breast Cancer Symposium 2021;. 2021. GS2-02
60 Wang N, Li X, Wang R. et al. Spatial transcriptomics and proteomics technologies for deconvoluting the tumor microenvironment. Biotechnol J 2021; 16: e2100041
61 Longo SK, Guo MG, Ji AL. et al. Integrating single-cell and spatial transcriptomics to elucidate intercellular tissue dynamics. Nat Rev Genet 2021; 22: 627-644
62 Bianchini G, Wang XQ, Danenberg E. et al Single-cell spatial analysis by imaging mass cytometry and immunotherapy response in triple-negative breast cancer (TNBC) in the NeoTRIPaPDL1 trial. San Antonio Breast Cancer Symposium 2021;. 2021. GS1-00
63 Keating SM, Taylor DL, Plant AL. et al. Opportunities and Challenges in Implementation of Multiparameter Single Cell Analysis Platforms for Clinical Translation. Clin Transl Sci 2018; 11: 267-276
64 Schmid P, Cortes J, Dent R. et al. Event-free Survival with Pembrolizumab in Early Triple-Negative Breast Cancer. N Engl J Med 2022;
65 Schmid P, Cortes J, Dent R. et al KEYNOTE‑522: Phase III study of neoadjuvant pembrolizumab + chemotherapy vs. placebo + chemotherapy, followed by adjuvant pembrolizumab vs. placebo for early-stage TNBC. Ann Oncol 2021; 32 VP7-2021
66 Schmid P, Cortes J, Dent R. et al KEYNOTE‑522: Phase 3 study of pembrolizumab + chemotherapy vs. placebo + chemotherapy as neoadjuvant treatment, followed by pembrolizumab vs. placebo as adjuvant treatment for early-stage high-risk triple-negative breast cancer (TNBC). San Antonio Breast Cancer Symposium 2021;. 2021. GS1-01
67 Fisher B, Costantino JP, Wickerham DL. et al. Tamoxifen for the prevention of breast cancer: current status of the National Surgical Adjuvant Breast and Bowel Project P‑1 study. J Natl Cancer Inst 2005; 97: 1652-1662
68 Powles TJ, Ashley S, Tidy A. et al. Twenty-year follow-up of the Royal Marsden randomized, double-blinded tamoxifen breast cancer prevention trial. J Natl Cancer Inst 2007; 99: 283-290
69 Cuzick J, Sestak I, Cawthorn S. et al. Tamoxifen for prevention of breast cancer: extended long-term follow-up of the IBIS‑I breast cancer prevention trial. Lancet Oncol 2015; 16: 67-75
70 Cuzick J, Sestak I, Forbes JF. et al. Use of anastrozole for breast cancer prevention (IBIS‑II): long-term results of a randomised controlled trial. Lancet 2020; 395: 117-122
71 Goss PE, Ingle JN, Ales-Martinez JE. et al. Exemestane for breast-cancer prevention in postmenopausal women. N Engl J Med 2011; 364: 2381-2391