Development of central nervous system metastases as a first site of metastatic disease in breast cancer patients treated in the neoadjuvant trials GeparQuinto and GeparSixto

  • Background: The incidence of central nervous system (CNS) metastases in breast cancer patients is rising and has become a major clinical challenge. Only few data are published concerning risk factors for the development of CNS metastases as a first site of metastatic disease in breast cancer patients. Moreover, the incidence of CNS metastases after modern neoadjuvant treatment is not clear. Methods: We analyzed clinical factors associated with the occurrence of CNS metastases as the first site of metastatic disease in breast cancer patients after neoadjuvant treatment in the trials GeparQuinto and GeparSixto (n = 3160) where patients received targeted treatment in addition to taxane and anthracycline-based chemotherapy. Results: After a median follow-up of 61 months, 108 (3%) of a total of 3160 patients developed CNS metastases as the first site of recurrence and 411 (13%) patients had metastatic disease outside the CNS. Thirty-six patients (1%) developed both CNS metastases and other distant metastases as the first site of metastatic disease. Regarding subtypes of the primary tumor, 1% of luminal A-like (11/954), 2% of luminal B-like (7/381), 4% of HER2-positive (34/809), and 6% of triple-negative patients (56/1008) developed CNS metastases as the first site of metastatic disease. In multivariate analysis, risk factors for the development of CNS metastases were larger tumor size (cT3–4; HR 1.63, 95% CI 1.08–2.46, p = 0.021), node-positive disease (HR 2.57, 95% CI 1.64–4.04, p < 0.001), no pCR after neoadjuvant chemotherapy (HR 2.29, 95% CI 1.32–3.97, p = 0.003), and HER2-positive (HR 3.80, 95% CI 1.89–7.64, p < 0.001) or triple-negative subtype (HR 6.38, 95% CI 3.28–12.44, p < 0.001). Conclusions: Especially patients with HER2-positive and triple-negative tumors are at risk of developing CNS metastases despite effective systemic treatment. A better understanding of the underlying mechanisms is required in order to develop potential preventive strategies.

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Author:Elena Laakmann, Isabell Witzel, Peter Andreas Fasching, Mahdi Rezai, Christian Schem, Christine Solbach, Hans Tesch, Peter Klare, Andreas Schneeweiss, Christoph Salat, Dirk-Michael Zahm, Jens-Uwe Blohmer, Barbara Ingold Heppner, Jens Huober, Claus Hanusch, Christian Jackisch, Mattea Reinisch, Michael Untch, Gunter von Minckwitz, Valentina Nekljudova, Volkmar MüllerGND, Sibylle Loibl
URN:urn:nbn:de:hebis:30:3-502532
DOI:https://doi.org/10.1186/s13058-019-1144-x
ISSN:1465-542X
ISSN:1465-5411
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/31077239
Parent Title (English):Breast cancer research
Publisher:BioMed Central
Place of publication:London
Document Type:Article
Language:English
Year of Completion:2019
Date of first Publication:2019/05/10
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2019/05/16
Tag:Breast cancer; Central nervous system metastases; First site of metastatic disease
Volume:21
Issue:1, Art. 60
Page Number:8
First Page:1
Last Page:8
Note:
Open Access: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
HeBIS-PPN:452426529
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0