Update Breast Cancer 2024 Part 1 – Expert Opinion on
                    Advanced Breast Cancer

Rachel Würstlein; Hans-Christian Kolberg; Andreas D. Hartkopf; Tanja N. Fehm; Manfred Welslau; Florian Schütz; Peter A. Fasching; Wolfgang Janni; Isabell Witzel; Christoph Thomssen; Annika Krückel; Erik Belleville; Diana Lüftner; Michael Untch; Marc Thill; Manuel Hörner; Hans Tesch; Nina Ditsch; Michael P. Lux; Bahriye Aktas; Maggie Banys-Paluchowski; Florin-Andrei Taran; Achim Wöckel; Nadia Harbeck; Elmar Stickeler; Rupert Bartsch; Andreas Schneeweiss; Johannes Ettl; David Krug; Volkmar Müller

doi:10.1055/a-2300-5326

Geburtshilfe und Frauenheilkunde, Table of Contents

CC BY-NC-ND 4.0 · Geburtshilfe Frauenheilkd 2024; 84(06): 529-540
DOI: 10.1055/a-2300-5326

GebFra Science

Review/Übersicht

Update Mammakarzinom 2024 Teil 1 – Expertenmeinungen zu Brustkrebs in fortgeschrittenen Krankheitsstadien

Article in several languages: English | deutsch

Rachel Würstlein

¹Breast Center, Department of Gynecology and Obstetrics and CCC Munich LMU, LMU University Hospital, Munich, Germany

,

Hans-Christian Kolberg

²Department of Gynecology and Obstetrics, Marienhospital Bottrop, Bottrop, Germany

,

Andreas D. Hartkopf

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

,

Tanja N. Fehm

⁴Department of Gynecology and Obstetrics, University Hospital Düsseldorf, Center for Integrated Oncology (CIO Aachen, Bonn, Cologne, Düsseldorf) Germany

,

Manfred Welslau

⁵Onkologie Aschaffenburg, Aschaffenburg, Germany

,

Florian Schütz

⁶Gynäkologie und Geburtshilfe, Diakonissen-Stiftungs-Krankenhaus Speyer, Speyer, Germany

,

Peter A. Fasching

⁷Erlangen University Hospital, Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany

,

Wolfgang Janni

⁸Department of Gynecology and Obstetrics, Ulm University Hospital, Ulm, Germany

,

Isabell Witzel

⁹Universitätsspital Zürich, Klinik für Gynäkologie, Zürich, Switzerland

,

Christoph Thomssen

¹⁰Department of Gynaecology, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany

,

Annika Krückel

⁷Erlangen University Hospital, Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany

,

Erik Belleville

¹¹ClinSol GmbH & Co. KG, Würzburg, Germany

,

Diana Lüftner

¹²Immanuel Hospital Märkische Schweiz, Buckow, Germany & Medical University of Brandenburg Theodor-Fontane, Rüdersdorf, Germany

,

Michael Untch

¹³Clinic for Gynecology and Obstetrics, Breast Cancer Center, Gynecologic Oncology Center, Helios Klinikum Berlin Buch, Berlin, Germany

,

Marc Thill

¹⁴Agaplesion Markus Krankenhaus, Department of Gynecology and Gynecological Oncology, Frankfurt, Germany

,

Manuel Hörner

⁷Erlangen University Hospital, Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany

,

Hans Tesch

¹⁵Oncology Practice at Bethanien Hospital, Frankfurt am Main, Germany

,

Nina Ditsch

¹⁶Department of Gynecology and Obstetrics, University Hospital Augsburg, Augsburg, Germany

,

Michael P. Lux

¹⁷Klinik für Gynäkologie und Geburtshilfe, Frauenklinik St. Louise, Paderborn, St. Josefs-Krankenhaus, Salzkotten, St. Vincenz Krankenhaus GmbH, Paderborn, Germany

,

Bahriye Aktas

¹⁸Department of Gynecology, University of Leipzig Medical Center, Leipzig, Germany

,

Maggie Banys-Paluchowski

¹⁹Department of Gynecology and Obstetrics, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany

,

Florin-Andrei Taran

²⁰Department of Gynecology and Obstetrics, University Hospital Freiburg, Freiburg, Germany

,

Achim Wöckel

²¹Department of Gynecology and Obstetrics, University Hospital Würzburg, Würzburg, Germany

,

Nadia Harbeck

¹Breast Center, Department of Gynecology and Obstetrics and CCC Munich LMU, LMU University Hospital, Munich, Germany

,

Elmar Stickeler

²²Department of Obstetrics and Gynecology, Center for Integrated Oncology (CIO Aachen, Bonn, Cologne, Düsseldorf), University Hospital of RWTH Aachen, Aachen, Germany

,

Rupert Bartsch

²³Medical University of Vienna, Department of Medicine I, Division of Oncology, Vienna, Austria

,

Andreas Schneeweiss

²⁴National Center for Tumor Diseases, University Hospital and German Cancer Research Center, Heidelberg, Germany

,

Johannes Ettl

²⁵Klinikum Kempten, Klinikverbund Allgäu, Klinik für Frauenheilkunde und Gynäkologie, Kempten, Germany

,

David Krug

²⁶Universitätsklinikum Schleswig-Holstein, Campus Kiel, Klinik für Strahlentherapie, Kiel, Germany

,

Volkmar Müller

²⁷Department of Gynecology, Hamburg-Eppendorf University Medical Center, Hamburg, Germany

› Author Affiliations

Abstract

Zusammenfassung

Klinische Evidenz wird auf Basis klinischer Studien und der persönlichen Erfahrung interpretiert. Dies kann in einer unterschiedlichen Deutung der Datenlage resultieren. Vor diesem Hintergrund sind Expertenpanels wie das Advanced Breast Cancer Panel, das im November 2023 zum 7. Mal zusammengekommen ist (ABC7), von besonderer Bedeutung. Aktuelle Themen werden von einem internationalen Expertenteam bewertet.

Im Jahr 2023 scheint sich die Datenlage zu den CDK4/6-Inhibitoren so verdichtet zu haben, dass Fragen zur Sequenz und zu einer möglichen Chemotherapie als Alternative relativ klar beantwortet werden können. Des Weiteren sind für alle molekularen Subtypen Daten zu Antikörper-Wirkstoff-Konjugaten vorhanden, sodass ein gutes Bild über deren Einsatz entstanden ist.

Einige Therapiesituationen sind nach wie vor von besonderer Bedeutung und sind strukturiert diskutiert worden, wie zum Beispiel Hirnmetastasen und leptomeningeale Erkrankung, ältere Patientinnen, das lokal fortgeschrittene Mammakarzinom und die viszerale Krise. Im Rahmen dieser Arbeit werden einige der diskutierten Themen im wissenschaftlichen Kontext dargestellt und bewertet.

Schlüsselwörter

Brustkrebs - metastasiert - endokrine Therapie - Antikörper-Wirkstoff-Konjugate - Chemotherapie

Full Text

References

References/Literatur
1 Diéras V, Miles D, Verma S. et al. Trastuzumab emtansine versus capecitabine plus lapatinib in patients with previously treated HER2-positive advanced breast cancer (EMILIA): a descriptive analysis of final overall survival results from a randomised, open-label, phase 3 trial. Lancet Oncol 2017; 18: 732-742
2 Verma S, Miles D, Gianni L. et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med 2012; 367: 1783-1791
3 Cortés J, Kim S-B, Chung W-P. et al. Trastuzumab deruxtecan versus trastuzumab emtansine for breast cancer. N Engl J Med 2022; 386: 1143-1154
4 Modi S, Saura C, Yamashita T. et al. Trastuzumab deruxtecan in previously treated HER2-positive breast cancer. N Engl J Med 2020; 382: 610-621
5 Rugo HS, Bardia A, Marmé F. et al. Overall survival with sacituzumab govitecan in hormone receptor-positive and human epidermal growth factor receptor 2-negative metastatic breast cancer (TROPiCS-02): a randomised, open-label, multicentre, phase 3 trial. Lancet 2023; 402: 1423-1433
6 Bardia A, Hurvitz SA, Tolaney SM. et al. Sacituzumab govitecan in metastatic triple-negative breast cancer. N Engl J Med 2021; 384: 1529-1541
7 Cortes J, Cescon DW, Rugo HS. et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet 2020; 396: 1817-1828
8 Cortes J, Rugo HS, Cescon DW. et al. Pembrolizumab plus Chemotherapy in Advanced Triple-Negative Breast Cancer. N Engl J Med 2022; 387: 217-226
9 Rugo HS, Loi S, Adams S. et al. Performance of PD-L1 immunohistochemistry (IHC) assays in unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC): Post-hoc analysis of IMpassion130. Ann Oncol 2019; 30: v858-v859
10 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
11 Schmid P, Rugo HS, Adams S. et al. Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 2020; 21: 44-59
12 Miles D, Gligorov J, André F. et al. Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase III trial of first-line paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer. Ann Oncol 2021; 32: 994-1004
13 Schneeweiss A, Brucker SY, Hübner HC. et al. CDK4/6 Inhibition – Therapy Sequences and the Quest for Finding the Best Biomarkers – an Overview of Current Programs. Geburtshilfe Frauenheilkd 2024;
14 Nabieva N, Fasching PA. CDK4/6 Inhibitors–Overcoming Endocrine Resistance Is the Standard in Patients with Hormone Receptor-Positive Breast Cancer. Cancers 2023; 15: 1763
15 Turner NC, Oliveira M, Howell SJ. et al. Capivasertib in hormone receptor–positive advanced breast cancer. N Engl J Med 2023; 388: 2058-2070
16 Jhaveri K, Im S-A, Saura C. et al. Inavolisib or placebo in combination with palbociclib and fulvestrant in patients with PIK3CA-mutated, hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer: Phase III, INAVO120 primary analysis. Proceedings of the 2023 San Antonio Breast Cancer Symposium, San Antonio, TX, USA 2023; 2023: 5-9
17 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
18 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
19 Hurvitz S, Quek R, Turner N. et al. Quality of life with talazoparib after platinum or multiple cytotoxic non-platinum regimens in patients with advanced breast cancer and germline BRCA1/2 mutations: patient-reported outcomes from the ABRAZO phase 2 trial. Eur J Cancer 2018; 104: 160-168
20 Robson M, Im S-A, Senkus E. et al. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med 2017; 377: 523-533
21 Ettl J, Quek R, Lee K-H. et al. Quality of life with talazoparib versus physicianʼs choice of chemotherapy in patients with advanced breast cancer and germline BRCA1/2 mutation: patient-reported outcomes from the EMBRACA phase III trial. Ann Oncol 2018; 29: 1939-1947
22 Robson M, Ruddy KJ, Seock-Ah I. et al. Patient-reported outcomes in patients with a germline BRCA mutation and HER2-negative metastatic breast cancer receiving olaparib versus chemotherapy in the OlympiAD trial. Eur J Cancer 2019; 120: 20-30
23 Engler T, Fasching PA, Lüftner D. et al. Implementation of CDK4/6 Inhibitors and its Influence on the Treatment Landscape of Advanced Breast Cancer Patients–Data from the Real-World Registry PRAEGNANT. Geburtshilfe Frauenheilkd 2022; 82: 1055-1067
24 Braun MSO, Salat C. et al. Current therapy landscape of advanced HER2 negative breast cancer in pateints in a network of office based internistic oncologists and gynecologic oncologists in Germany. Deutscher Krebskongress 2022; 2022: Abstr.. 306
25 AGO Kommission Mamma. Diagnostik und Therapie früher und fortgeschrittener Mammakarzinome: Therapiealgorithmen. 2024 Online (Stand: 25.03.2024): https://www.ago-online.de/leitlinien-empfehlungen/leitlinien-empfehlungen/kommission-mamma
26 Cardoso F, Paluch-Shimon S, Senkus E. et al. 5th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC5). Ann Oncol 2020; 31: 1623-1649
27 Lu Y-S, Mahidin EIBM, Azim H. et al. Primary results from the randomized Phase II RIGHT Choice trial of premenopausal patients with aggressive HR+/HER2− advanced breast cancer treated with ribociclib + endocrine therapy vs physician’s choice combination chemotherapy. Presented at SABCS 2022. December 6–10, 2022. Abstract GS1-10.
28 Ma H, Lu Y, Marchbanks PA. et al. Quantitative measures of estrogen receptor expression in relation to breast cancer-specific mortality risk among white women and black women. Breast Cancer Res 2013; 15: 1-12
29 Azim H, El Saghir N, Yap Y. et al. 402P First-line ribociclib (RIB)+ endocrine therapy (ET) vs. combination chemotherapy (combo CT) in aggressive HR+/HER2− advanced breast cancer (ABC): A subgroup analysis of patients (pts) with or without visceral crisis from the phase II RIGHT choice study. Ann Oncol 2023; 34: S350-S351
30 Schneeweiss A, Ettl J, Lüftner D. et al. Initial experience with CDK4/6 inhibitor-based therapies compared to antihormone monotherapies in routine clinical use in patients with hormone receptor positive, HER2 negative breast cancer–Data from the PRAEGNANT research network for the first 2 years of drug availability in Germany. Breast 2020; 54: 88-95
31 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
32 Hartkopf AD, Huober J, Volz B. et al. Treatment landscape of advanced breast cancer patients with hormone receptor positive HER2 negative tumors–Data from the German PRAEGNANT breast cancer registry. Breast 2018; 37: 42-51
33 Sonke GS, Van Ommen-Nijhof A, Wortelboer N. et al. Primary outcome analysis of the phase 3 SONIA trial (BOOG 2017-03) on selecting the optimal position of cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors for patients with hormone receptor-positive (HR+), HER2-negative (HER2-) advanced breast cancer (ABC). JCO 2023; 41 (Suppl.) LBA1000
34 Finn RS, Rugo HS, Dieras VC. et al. Overall survival (OS) with first-line palbociclib plus letrozole (PAL+LET) versus placebo plus letrozole (PBO+LET) in women with estrogen receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer (ER+/HER2− ABC): Analyses from PALOMA-2. JCO 2022; 40 (Suppl.) LBA1003
35 Kalinsky K, Accordino MK, Chiuzan C. et al. Randomized phase II trial of endocrine therapy with or without ribociclib after progression on cyclin-dependent kinase 4/6 inhibition in hormone receptor–positive, human epidermal growth factor receptor 2–negative metastatic breast cancer: Maintain trial. J Clin Oncol 2023; 41: 4004-4013
36 Mayer EL, Ren Y, Wagle N. et al. Abstract Gs3-06: Gs3-06 Palbociclib after Cdk4/6I and endocrine therapy (PACE): A randomized phase II study of Fulvestrant, Palbociclib, and Avelumab for endocrine pre-treated ER+/Her2-metastatic breast cancer. Cancer Res 2023; 83(5_Supplement): GS3-06
37 Bidard F-C, Kaklamani VG, Neven P. et al. Elacestrant (oral selective estrogen receptor degrader) versus standard endocrine therapy for estrogen receptor–positive, human epidermal growth factor receptor 2–negative advanced breast cancer: results from the randomized phase III EMERALD trial. J Clin Oncol 2022; 40: 3246
38 Clinicaltrials.gov. Study of Trastuzumab Deruxtecan (T-DXd) vs. Investigatorʼs Choice Chemotherapy in HER2-low, Hormone Receptor Positive, Metastatic Breast Cancer (DB-06). 2024 Online (Stand: 24.01.2024): https://clinicaltrials.gov/study/NCT04494425
39 Modi S, Jacot W, Yamashita T. et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med 2022; 387: 9-20
40 Bardia A, Jhaveri K, Im S. et al. LBA11 Datopotamab deruxtecan (Dato-DXd) vs. chemotherapy in previously-treated inoperable or metastatic hormone receptor-positive, HER2-negative (HR+/HER2–) breast cancer (BC): Primary results from the randomised phase III TROPION-Breast01 trial. Ann Oncol 2023; 34: S1264-S1265
41 Murthy RK, Loi S, Okines A. et al. Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer. N Engl J Med 2020; 382: 597-609
42 Curigliano G, Mueller V, Borges V. et al. Tucatinib versus placebo added to trastuzumab and capecitabine for patients with pretreated HER2+ metastatic breast cancer with and without brain metastases (HER2CLIMB): final overall survival analysis. Ann Oncol 2022; 33: 321-329
43 Hurvitz S, Modi S, Li W. et al. 377O A pooled analysis of trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-positive (HER2+) metastatic breast cancer (mBC) with brain metastases (BMs) from DESTINY-Breast (DB)-01,-02, and-03. Ann Oncol 2023; 34: S335-S336
44 Miglietta F, Visani L, Marini S. et al. Oligometastatic breast cancer: Dissecting the clinical and biological uniqueness of this emerging entity. Can we pursue curability?. Cancer Treat Rev 2022; 110: 102462
45 Palma DA, Olson R, Harrow S. et al. Stereotactic ablative radiotherapy for the comprehensive treatment of oligometastatic cancers: long-term results of the SABR-COMET phase II randomized trial. J Clin Oncol 2020; 38: 2830
46 Chmura SJ, Winter KA, Woodward WA. et al. NRG-BR002: A phase IIR/III trial of standard of care systemic therapy with or without stereotactic body radiotherapy (SBRT) and/or surgical resection (SR) for newly oligometastatic breast cancer (NCT02364557). JCO 2022; 40 (Suppl.) 1007
47 Müller V, Hein A, Hartkopf AD. et al. Occurrence and characteristics of patients with de novo advanced breast cancer according to patient and tumor characteristics–A retrospective analysis of a real world registry. Eur J Cancer 2022; 172: 13-21
48 Caglevic C, Rolfo C, Gil-Bazo I. et al. The armed conflict and the impact on patients with cancer in Ukraine: Urgent considerations. JCO Glob Oncol 2022; 8: e2200123
49 van Leeuwen RW, Jansman FG, van den Bemt PM. et al. Drug–drug interactions in patients treated for cancer: a prospective study on clinical interventions. Ann Oncol 2015; 26: 992-997
50 Poggio F, Tagliamento M, Pirrone C. et al. Update on the management of breast cancer during pregnancy. Cancers 2020; 12: 3616
51 Loibl S, Han SN, von Minckwitz G. et al. Treatment of breast cancer during pregnancy: an observational study. Lancet Oncol 2012; 13: 887-896
52 Amant F, von Minckwitz G, Han SN. et al. Prognosis of women with primary breast cancer diagnosed during pregnancy: results from an international collaborative study. J Clin Oncol 2013; 31: 2532-2539
53 Loibl S, Schmidt A, Gentilini O. et al. Breast cancer diagnosed during pregnancy: adapting recent advances in breast cancer care for pregnant patients. JAMA Oncol 2015; 1: 1145-1153
54 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(Suppl): LBA2
55 Loibl S, Azim jr. HA, Bachelot T. et al. ESMO Expert Consensus Statements on the management of breast cancer during pregnancy (PrBC). Ann Oncol 2023; 34: 849-866

Supplementary Material