Zerebrale Metastasierung beim Mammakarzinom

Zusammenfassung

Die Inzidenz von Hirnmetastasen beim Mammakarzinom ist in den letzten Jahren stetig gestiegen. Hirnmetastasen stellen oft den limitierenden Faktor der Erkrankung dar, da das Überleben nach Auftreten einer Hirnmetastasierung meist nur wenige Monate beträgt. Neben der schlechten Prognose kommt es aufgrund kognitiver und neurologischer Defizite zu einer massiven Einschränkung der Lebensqualität. HER2-positive oder triple-negative Karzinome entwickeln häufiger Hirnmetastasen. Untersuchungen zum Thema Hirnmetastasen wurden meist an Kohorten mit unterschiedlichen Primärtumoren durchgeführt. Um die Datenlage bei Patientinnen mit Mammakarzinom zu verbessern, wurde das Register „Brain Metastases in Breast Cancer (BMBC)“ zur Erfassung der deutschen Versorgungsrealität initiiert. Aufgrund der fehlenden spezifischen systemischen Therapieoptionen steht die lokale Therapie der Hirnmetastasen (Operation, stereotaktische Bestrahlung, Ganzhirnbestrahlung) zunächst im Vordergrund. Die lokale Therapie wird durch eine systemische Therapie ergänzt. Die Wahl der systemischen Therapie richtet sich v. a. nach der extrakraniellen Erkrankungssituation, da es derzeit praktisch keine Studiendaten speziell zur systemischen Therapie von Hirnmetastasen gibt. Erst in letzter Zeit werden Substanzen in Studien explizit bei Frauen mit Hirnmetastasen eines Mammakarzinoms untersucht.

Schlüsselworter

Mammakarzinom - Hirnmetastasen - Strahlentherapie - systemische Therapie

Key words

breast cancer - brain metastasis - radiotherapy - systemic therapy

• References

• 1 Quail DF, Joyce JA. Microenvironmental regulation of tumor progression and metastasis. Nat Med 2013; 19: 1423-1437 . doi:10.1038/nm.3394
• 2 Soni A, Ren Z, Hameed O. et al. Breast cancer subtypes predispose the site of distant metastases. Am J Clin Pathol 2015; 143: 471-478 . doi:10.1309/ajcpyo5fsv3upexs
• 3 Kang Y, Pantel K. Tumor cell dissemination: emerging biological insights from animal models and cancer patients. Cancer Cell 2013; 23: 573-581 . doi:10.1016/j.ccr.2013.04.017
• 4 Pedrosa R, Mustafa DA, Soffietti R. et al. Breast cancer brain metastasis: molecular mechanisms and directions for treatment. Neuro Oncol 2018;
• 5 Zhang C, Yu D. Microenvironment determinants of brain metastasis. Cell Biosci 2011; 1: 8 . doi:10.1186/2045-3701-1-8
• 6 Reese TS, Karnovsky MJ. Fine structural localization of a blood-brain barrier to exogenous peroxidase. J Cell Biol 1967; 34: 207-217
• 7 Witzel I, Oliveira-Ferrer L, Pantel K. et al. Breast cancer brain metastases: biology and new clinical perspectives. Breast Cancer Res 2016; 18: 8 . doi:10.1186/s13058-015-0665-1
• 8 Arvold ND, Oh KS, Niemierko A. et al. Brain metastases after breast-conserving therapy and systemic therapy: incidence and characteristics by biologic subtype. Breast Cancer Res Treat 2012; 136: 153-160 . doi:10.1007/s10549-012-2243-x
• 9 Laakmann E, Witzel I, Fasching PA. et al. Hirnmetastasierung bei Patientinnen mit Mammakarzinom nach einer neoadjuvanten Chemotherapie. Senologie – Zeitschrift für Mammadiagnostik und -therapie 2018; 15 (02) e30 . doi: 10.1055/s-0038-1651754
• 10 Witzel I, Kantelhardt EJ, Milde-Langosch K. et al. Management of patients with brain metastases receiving trastuzumab treatment for metastatic breast cancer. Onkologie 2011; 34: 304-308 . doi:10.1159/000328679
• 11 Yau T, Swanton C, Chua S. et al. Incidence, pattern and timing of brain metastases among patients with advanced breast cancer treated with trastuzumab. Acta Oncol 2006; 45: 196-201 . doi:10.1080/02841860500486630
• 12 Laakmann E, Witzel I, Scriba V. et al. Radiological Patterns of Brain Metastases in Breast Cancer Patients: A Subproject of the German Brain Metastases in Breast Cancer (BMBC) Registry. Int J Mol Sci 2016; 17
• 13 Morikawa A, Jordan L, Rozner R. et al. Characteristics and Outcomes of Patients With Breast Cancer With Leptomeningeal Metastasis. Clin Breast Cancer 2017; 17: 23-28 . doi:10.1016/j.clbc.2016.07.002
• 14 Niikura N, Hayashi N, Masuda N. et al. Treatment outcomes and prognostic factors for patients with brain metastases from breast cancer of each subtype: a multicenter retrospective analysis. Breast Cancer Res Treat 2014; 147: 103-112 . doi:10.1007/s10549-014-3090-8
• 15 Thill M, Liedtke C, Müller V. et al. AGO Recommendations for the Diagnosis and Treatment of Patients with Advanced and Metastatic Breast Cancer: Update 2018. Breast Care 2018; 13: 209-215 . doi: 10.1159/000489331
• 16 Harbeck N, Luftner D, Marschner N. et al. ABC4 Consensus: Assessment by a German Group of Experts. Breast Care (Basel) 2018; 13: 48-58 . doi:10.1159/000486722
• 17 Witzel I. Treatment and outcomes of patients in the Brain Metastases in Breast Cancer Network Registry. European Journal of Cancer 2018; 102: 1-9
• 18 Brown PD, Ballman KV, Cerhan JH. et al. Postoperative stereotactic radiosurgery compared with whole brain radiotherapy for resected metastatic brain disease (NCCTG N107C/CEC.3): a multicentre, randomised, controlled, phase 3 trial. Lancet Oncol 2017; 18: 1049-1060 . doi:10.1016/s1470-2045(17)30441-2
• 19 Kocher M, Soffietti R, Abacioglu U. et al. Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: results of the EORTC 22952-26001 study. J Clin Oncol 2011; 29: 134-141 . doi:10.1200/JCO.2010.30.1655
• 20 Brown PD, Jaeckle K, Ballman KV. et al. Effect of Radiosurgery Alone vs Radiosurgery With Whole Brain Radiation Therapy on Cognitive Function in Patients With 1 to 3 Brain Metastases: A Randomized Clinical Trial. Jama 2016; 316: 401-409 . doi:10.1001/jama.2016.9839
• 21 Stemmler HJ, Mengele K, Schmitt M. et al. Intrathecal trastuzumab (Herceptin) and methotrexate for meningeal carcinomatosis in HER2-overexpressing metastatic breast cancer: a case report. Anticancer Drugs 2008; 19: 832-836
• 22 Niwinska A, Murawska M, Pogoda K. Breast cancer brain metastases: differences in survival depending on biological subtype, RPA RTOG prognostic class and systemic treatment after whole-brain radiotherapy (WBRT). Ann Oncol 2010; 21: 942-948 . doi:10.1093/annonc/mdp407
• 23 Swain SM, Baselga J, Miles D. et al. Incidence of central nervous system metastases in patients with HER2-positive metastatic breast cancer treated with pertuzumab, trastuzumab, and docetaxel: results from the randomized phase III study CLEOPATRA. Ann Oncol 2014; 25: 1116-1121 . doi:10.1093/annonc/mdu133
• 24 Krop IE, Lin NU, Blackwell K. et al. Trastuzumab emtansine (T-DM1) versus lapatinib plus capecitabine in patients with HER2-positive metastatic breast cancer and central nervous system metastases: a retrospective, exploratory analysis in EMILIA. Ann Oncol 2015; 26: 113-119 . doi:10.1093/annonc/mdu486
• 25 Bartsch R, Berghoff AS, Vogl U. et al. Activity of T-DM1 in Her2-positive breast cancer brain metastases. Clin Exp Metastasis 2015; 32: 729-737 . doi:10.1007/s10585-015-9740-3
• 26 Borges VF, Ferrario C, Aucoin N. et al. Tucatinib Combined With Ado-Trastuzumab Emtansine in Advanced ERBB2 / HER2-Positive Metastatic Breast Cancer: A Phase 1b Clinical Trial. JAMA oncology 2018;
• 27 Cortes J, Rugo HS, Awada A. et al. Prolonged survival in patients with breast cancer and a history of brain metastases: results of a preplanned subgroup analysis from the randomized phase III BEACON trial. Breast Cancer Res Treat 2017; 165: 329-341 . doi:10.1007/s10549-017-4304-7
• 28 Yamamoto D, Iwase S, Tsubota Y. et al. Bevacizumab in the treatment of five patients with breast cancer and brain metastases: Japan Breast Cancer Research Network-07 trial. OncoTargets and therapy 2012; 5: 185-189 . doi:10.2147/ott.s36515
• 29 Lu YS, Chen TW, Lin CH. et al. Bevacizumab Preconditioning Followed by Etoposide and Cisplatin Is Highly Effective in Treating Brain Metastases of Breast Cancer Progressing from Whole-Brain Radiotherapy. Clin Cancer Res 2015;
• 30 Chen BB, Lu YS, Lin CH. et al. A pilot study to determine the timing and effect of bevacizumab on vascular normalization of metastatic brain tumors in breast cancer. BMC Cancer 2016; 16: 466 . doi:10.1186/s12885-016-2494-8
• 31 Sara MTolaney NUL, Donald Thornton, Suzanne Klise. et al. Abemaciclib for the treatment of brain metastases (BM) secondary to hormone receptor positive (HR+), HER2 negative breast cancer. ASCO 2017 (abs 1019)