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DOI: 10.1055/a-1811-6148
Update Mammakarzinom 2022 Teil 2 – Brustkrebs in fortgeschrittenen Krankheitsstadien
Article in several languages: English | deutsch![](https://www.thieme-connect.de/media/gebfra/202206/lookinside/thumbnails/10-1055-a-1811-6148_gf_de-1.jpg)
Zusammenfassung
Für Patientinnen mit einem fortgeschrittenen Mammakarzinom sind in den letzten Jahren mit den CDK4/6-Inhibitoren, den Immuncheckpoint-Inhibitoren, den PARP-Inhibitoren, dem Alpelisib, Tucatinib und Trastuzumab-Deruxtecan sowie Sacituzumab-Govitecan einige Therapien neu etabliert worden, welche die Therapielandschaft von Patientinnen mit einem fortgeschrittenen Mammakarzinom deutlich verändert bzw. erweitert haben. Einige dieser Substanzen sind mittlerweile auch bei frühen Krankheitsstadien zugelassen bzw. eine Zulassung ist in naher Zukunft wahrscheinlich, sodass sich die Therapielandschaft abermals ändern wird. Die Einführung neuer Substanzen und das Verständnis der Progressions- und Effektivitätsmechanismen für diese Substanzen steht deswegen im Fokus der aktuellen wissenschaftlichen Bemühungen. In dieser Übersichtsarbeit werden die neuen Entwicklungen basierend auf aktuellen Publikationen und Kongressen zusammengefasst. Erkenntnisse zur Behandlung von Patientinnen mit einem HER2-positiven Mammakarzinom und Hirnmetastasen werden ebenso dargestellt wie eine Reihe von Studien, die sich mit Biomarkern bei Patientinnen mit HER2-negativem, hormonrezeptorpositivem Mammakarzinom beschäftigen. Insbesondere die Einführung der oralen, selektiven Östrogenrezeptor-Degradierer birgt neue Chancen, eine biomarkerbasierte Therapie zu etablieren. Die molekulare Diagnostik etabliert sich als diagnostischer Marker und Verlaufsparameter.
Publication History
Received: 21 March 2022
Accepted after revision: 26 March 2022
Article published online:
03 June 2022
© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)
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References/Literatur
- 1 Brett JO, Spring LM, Bardia A. et al. ESR1 mutation as an emerging clinical biomarker in metastatic hormone receptor-positive breast cancer. Breast Cancer Res 2021; 23: 85 DOI: 10.1186/s13058-021-01462-3.
- 2 OʼLeary B, Cutts RJ, Huang X. et al. Circulating Tumor DNA Markers for Early Progression on Fulvestrant With or Without Palbociclib in ER+ Advanced Breast Cancer. J Natl Cancer Inst 2021; 113: 309-317 DOI: 10.1093/jnci/djaa087.
- 3 OʼLeary B, Cutts RJ, Liu Y. et al. The Genetic Landscape and Clonal Evolution of Breast Cancer Resistance to Palbociclib plus Fulvestrant in the PALOMA-3 Trial. Cancer Discov 2018; 8: 1390-1403 DOI: 10.1158/2159-8290.CD-18-0264.
- 4 Bidard F, Hardy-Bessard A, Bachelot T. et al. Fulvestrant-palbociclib vs. continuing aromatase inhibitor-palbociclib upon detection of circulating ESR1 mutation in HR+ HER2- metastatic breast cancer patients: Results of PADA-1, a UCBG-GINECO randomized phase 3 trial. San Antonio Breast Cancer Symposium 2021; 2021: GS3-05
- 5 clinicaltrials.gov. Phase III Study to Assess AZD9833+ CDK4/6 Inhibitor in HR+/HER2-MBC With Detectable ESR1m Before Progression (SERENA-6) (SERENA-6). 2021. Accessed October 24, 2021 at: https://clinicaltrials.gov/ct2/show/NCT04964934
- 6 Lüftner D, Schütz F, Stickeler E. et al. Update Breast Cancer 2021 Part 5 – Advanced Breast Cancer. Geburtshilfe Frauenheilkd 2022; DOI: 10.1055/a-1724-9569.
- 7 Nabieva N, Haberle L, Brucker SY. et al. Preexisting musculoskeletal burden and its development under letrozole treatment in early breast cancer patients. Int J Cancer 2019; 145: 2114-2121 DOI: 10.1002/ijc.32294.
- 8 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
- 9 European Medicines Agency. Summary of product characteristics (SmPC). 2022. Accessed March 26, 2022 at: https://www.ema.europa.eu/en/documents/product-information/verzenios-epar-product-information_en.pdf
- 10 Collins JM, Nordstrom BL, McLaurin KK. et al. A Real-World Evidence Study of CDK4/6 Inhibitor Treatment Patterns and Outcomes in Metastatic Breast Cancer by Germline BRCA Mutation Status. Oncol Ther 2021; DOI: 10.1007/s40487-021-00162-4.
- 11 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 DOI: 10.1200/JCO.20.01200.
- 12 Hortobagyi GN, Stemmer SM, Burris HA. et al. Overall survival (OS) results from the phase III MONALEESA-2 (ML-2) trial of postmenopausal patients (pts) with hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2 L) advanced breast cancer (ABC) treated with endocrine therapy (ET) ± ribociclib (RIB). Ann Oncol 2021; 32: S1290-S1291 DOI: 10.1016/j.annonc.2021.08.2090.
- 13 Hortobagyi GN, Stemmer SM, Burris HA. et al. Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer. N Engl J Med 2016; 375: 1738-1748 DOI: 10.1056/NEJMoa1609709.
- 14 Hortobagyi GN, Stemmer SM, Burris HA. et al. Updated results from MONALEESA-2, a phase III trial of first-line ribociclib plus letrozole versus placebo plus letrozole in hormone receptor-positive, HER2-negative advanced breast cancer. Ann Oncol 2018; 29: 1541-1547 DOI: 10.1093/annonc/mdy155.
- 15 Slamon DJ, Neven P, Chia S. et al. Overall Survival with Ribociclib plus Fulvestrant in Advanced Breast Cancer. N Engl J Med 2020; 382: 514-524 DOI: 10.1056/NEJMoa1911149.
- 16 Slamon DJ, Neven P, Chia S. et al. Phase III Randomized Study of Ribociclib and Fulvestrant in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: MONALEESA-3. J Clin Oncol 2018; DOI: 10.1200/JCO.2018.78.9909.
- 17 Slamon DJ, Neven P, Chia S. et al. Ribociclib plus fulvestrant for postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer in the phase III randomized MONALEESA-3 trial: updated overall survival. Ann Oncol 2021; 32: 1015-1024 DOI: 10.1016/j.annonc.2021.05.353.
- 18 Im SA, Lu YS, Bardia A. et al. Overall Survival with Ribociclib plus Endocrine Therapy in Breast Cancer. N Engl J Med 2019; 381: 307-316 DOI: 10.1056/NEJMoa1903765.
- 19 Tripathy D, Im SA, Colleoni M. et al. Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial. Lancet Oncol 2018; DOI: 10.1016/S1470-2045(18)30292-4.
- 20 Sledge jr. GW, Toi M, Neven P. et al. The Effect of Abemaciclib Plus Fulvestrant on Overall Survival in Hormone Receptor-Positive, ERBB2-Negative Breast Cancer That Progressed on Endocrine Therapy-MONARCH 2: A Randomized Clinical Trial. JAMA Oncol 2019; DOI: 10.1001/jamaoncol.2019.4782.
- 21 Sledge jr. GW, Toi M, Neven P. et al. MONARCH 2: Abemaciclib in Combination With Fulvestrant in Women With HR+/HER2- Advanced Breast Cancer Who Had Progressed While Receiving Endocrine Therapy. J Clin Oncol 2017; 35: 2875-2884 DOI: 10.1200/JCO.2017.73.7585.
- 22 Goetz MP, Toi M, Campone M. et al. MONARCH 3: Abemaciclib As Initial Therapy for Advanced Breast Cancer. J Clin Oncol 2017; 35: 3638-3646 DOI: 10.1200/JCO.2017.75.6155.
- 23 Finn RS, Crown JP, Lang I. et al. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol 2015; 16: 25-35 DOI: 10.1016/S1470-2045(14)71159-3.
- 24 Finn RS, Martin M, Rugo HS. et al. Palbociclib and Letrozole in Advanced Breast Cancer. N Engl J Med 2016; 375: 1925-1936 DOI: 10.1056/NEJMoa1607303.
- 25 Cristofanilli M, Turner NC, Bondarenko I. et al. Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial. Lancet Oncol 2016; 17: 425-439 DOI: 10.1016/S1470-2045(15)00613-0.
- 26 Turner NC, Ro J, Andre F. et al. Palbociclib in Hormone-Receptor-Positive Advanced Breast Cancer. N Engl J Med 2015; 373: 209-219 DOI: 10.1056/NEJMoa1505270.
- 27 Turner NC, Slamon DJ, Ro J. et al. Overall Survival with Palbociclib and Fulvestrant in Advanced Breast Cancer. N Engl J Med 2018; 379: 1926-1936 DOI: 10.1056/NEJMoa1810527.
- 28 Schneeweiss A, Ettl J, Luftner 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 DOI: 10.1016/j.breast.2020.08.011.
- 29 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 DOI: 10.1016/j.breast.2017.10.002.
- 30 Bianchini G, Malorni L, Arpino G. et al. Circulating tumor DNA (ctDNA) dynamics in patients with hormone receptor positive (HR+)/HER2 negative (HER2-) advanced breast cancer (aBC) treated in first line with ribociclib (R) and letrozole (L) in the BioItaLEE trial. San Antonio Breast Cancer Symposium 2021; 2021: GS3-07
- 31 André F, Gonçalves A, Filleron T. et al. Clinical utility of molecular tumor profiling: Results from the randomized trial SAFIR02-BREAST. San Antonio Breast Cancer Symposium 2021; 2021: GS1-10
- 32 Mateo J, Chakravarty D, Dienstmann R. et al. A framework to rank genomic alterations as targets for cancer precision medicine: the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT). Ann Oncol 2018; 29: 1895-1902 DOI: 10.1093/annonc/mdy263.
- 33 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 DOI: 10.1056/NEJMoa1706450.
- 34 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 DOI: 10.1016/S0140-6736(20)32531-9.
- 35 Cortes J, Cescon DW, Rugo HS. et al. Final results of KEYNOTE-355: Randomized, double-blind, phase 3 study of pembrolizumab + chemotherapy vs. placebo + chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer. San Antonio Breast Cancer Symposium 2021; 2021: GS1-02
- 36 Bardia A, Hurvitz SA, Tolaney SM. et al. Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer. N Engl J Med 2021; 384: 1529-1541 DOI: 10.1056/NEJMoa2028485.
- 37 Goldenberg DM, Stein R, Sharkey RM. The emergence of trophoblast cell-surface antigen 2 (TROP-2) as a novel cancer target. Oncotarget 2018; 9: 28989-29006 DOI: 10.18632/oncotarget.25615.
- 38 Zaman S, Jadid H, Denson AC. et al. Targeting Trop-2 in solid tumors: future prospects. Onco Targets Ther 2019; 12: 1781-1790 DOI: 10.2147/OTT.S162447.
- 39 Vranic S, Gatalica Z. Trop-2 protein as a therapeutic target: A focused review on Trop-2-based antibody-drug conjugates and their predictive biomarkers. Bosn J Basic Med Sci 2022; 22: 14-21 DOI: 10.17305/bjbms.2021.6100.
- 40 Liao S, Wang B, Zeng R. et al. Recent advances in trophoblast cell-surface antigen 2 targeted therapy for solid tumors. Drug Dev Res 2021; 82: 1096-1110 DOI: 10.1002/ddr.21870.
- 41 Krop I, Juric D, Shimizu T. et al. Datopotamab deruxtecan in advanced/metastatic HER2- breast cancer: Results from the phase 1 TROPION-PanTumor01 study. San Antonio Breast Cancer Symposium 2021; 2021: GS1-05
- 42 Marme F. Phase-III-Studie zur postneoadjuvantenBehandlung mit dem Antikörper-Medikamenten-KonjugatSacituzumab Govitecan bei Frauen mit frühem, HER2-negativem Brustkrebs und hohem Rückfallrisiko nach einer Standardbehandlung im neoadjuvantenSetting -SASCIA. 2020. Accessed July 16, 2020 at: https://www.gbg.de/wAssets/docs/events-vortraege/2020_JT/23_SASCIA.pdf
- 43 Lin NU, Borges V, Anders C. et al. Intracranial Efficacy and Survival With Tucatinib Plus Trastuzumab and Capecitabine for Previously Treated HER2-Positive Breast Cancer With Brain Metastases in the HER2CLIMB Trial. J Clin Oncol 2020; 38: 2610-2619 DOI: 10.1200/JCO.20.00775.
- 44 Hurvitz S, Kim SB, Chung WP. et al. Trastuzumab deruxtecan vs. trastuzumab emtansine in patients with HER2+ metastatic breast cancer: Results of the randomized phase 3 study DESTINY-Breast03. San Antonio Breast Cancer Symposium 2021; 2021: GS3-01
- 45 Montemurro F, Delaloge S, Barrios CH. et al. Trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer and brain metastases: exploratory final analysis of cohort 1 from KAMILLA, a single-arm phase III b clinical trial(). Ann Oncol 2020; 31: 1350-1358 DOI: 10.1016/j.annonc.2020.06.020.
- 46 clinicaltrials.gov. DS-8201a Versus T-DM1 for Human Epidermal Growth Factor Receptor 2 (HER2)-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane [DESTINY-Breast03]. 2022. Accessed February 01, 2022 at: https://clinicaltrials.gov/ct2/show/NCT03529110
- 47 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 DOI: 10.1056/NEJMoa1914609.
- 48 Liao S, Wang B, Zeng R. et al. Recent advances in trophoblast cell-surface antigen 2 targeted therapy for solid tumors. Preprints 2020; DOI: 10.20944/preprints202012.0062.v1.