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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

Laakmann, Elena ; Witzel, Isabell ; Fasching, Peter A. ; Rezai, Mahdi ; Schem, Christian ; Solbach, Christine ; Tesch, Hans ; Klare, Peter ; Schneeweiss, Andreas ; Salat, Christoph ; Zahm, Dirk-Michael ; Blohmer, Jens-Uwe ; Ingold-Heppner, Barbara ; Huober, Jens ; Hanusch, Claus ; Jackisch, Christian ; Reinisch, Mattea ; Untch, Michael ; von Minckwitz, Gunter ; Nekljudova, Valentina ; Müller, Volkmar ; Loibl, Sibylle

In: Breast Cancer Research, 21 (2019), Nr. 60. pp. 1-8. ISSN 1465-5411

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Download (629kB) | Lizenz: Creative Commons LizenzvertragDevelopment of central nervous system metastases as a first site of metastatic disease in breast cancer patients treated in the neoadjuvant trials GeparQuinto and GeparSixto by Laakmann, Elena ; Witzel, Isabell ; Fasching, Peter A. ; Rezai, Mahdi ; Schem, Christian ; Solbach, Christine ; Tesch, Hans ; Klare, Peter ; Schneeweiss, Andreas ; Salat, Christoph ; Zahm, Dirk-Michael ; Blohmer, Jens-Uwe ; Ingold-Heppner, Barbara ; Huober, Jens ; Hanusch, Claus ; Jackisch, Christian ; Reinisch, Mattea ; Untch, Michael ; von Minckwitz, Gunter ; Nekljudova, Valentina ; Müller, Volkmar ; Loibl, Sibylle underlies the terms of Creative Commons Attribution 4.0

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Abstract

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.

Item Type: Article
Journal or Publication Title: Breast Cancer Research
Volume: 21
Number: 60
Publisher: BioMed Central
Place of Publication: London
Date Deposited: 01 Aug 2019 15:30
Date: 2019
ISSN: 1465-5411
Page Range: pp. 1-8
Faculties / Institutes: Service facilities > German Cancer Research Center (DKFZ)
Subjects: 610 Medical sciences Medicine
Uncontrolled Keywords: Central nervous system metastases, Breast cancer, First site of metastatic disease
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