TY  - JOUR
A1  - Laakmann, Elena
A1  - Witzel, Isabell
A1  - Fasching, Peter Andreas
A1  - Rezai, Mahdi
A1  - Schem, Christian
A1  - Solbach, Christine
A1  - Tesch, Hans
A1  - Klare, Peter
A1  - Schneeweiss, Andreas
A1  - Salat, Christoph
A1  - Zahm, Dirk-Michael
A1  - Blohmer, Jens-Uwe
A1  - Ingold Heppner, Barbara
A1  - Huober, Jens
A1  - Hanusch, Claus
A1  - Jackisch, Christian
A1  - Reinisch, Mattea
A1  - Untch, Michael
A1  - Minckwitz, Gunter von
A1  - Nekljudova, Valentina
A1  - Müller, Volkmar
A1  - Loibl, Sibylle
T1  - 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
T2  - Breast cancer research
N2  - 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.
KW  - Central nervous system metastases
KW  - Breast cancer
KW  - First site of metastatic disease
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/50253
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-502532
SN  - 1465-542X
SN  - 1465-5411
N1  - 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.
VL  - 21
IS  - 1, Art. 60
SP  - 1
EP  - 8
PB  - BioMed Central
CY  - London
ER  -