Artikel
Taxane treatment reduces peripheral tumor growth but is associated with increased CNS metastases in a murine model of HER2-positive breast cancer
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Veröffentlicht: | 11. September 2012 |
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Gliederung
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Breast cancer is the most frequent neoplasm in females and frequently associated with CNS-metastases. While the overall incidence of CNS-metastases reaches approximately 15%, much higher rates are observed in patients with HER2-positive breast cancer or receiving taxane treatment up to finally reaching a metastasis rate of 30 to 50%. To elucidate the role of taxane treatment on CNS metastases, we investigated the MDA-MB-231-BR cell line in a murine breast cancer model. In a first approach, we could show that docetaxel treatment of Balb/c nude mice significantly reduced the number of peripheral metastases of MDA-MB-231-BR tumors already in a small cohort (n=9; p=0.0297). Subsequently, mice were injected intravenously with docetaxel at a dose of 10mg/kg every 2 weeks for 5 injections (long tax, N=17) or with only 2 similar injections (short tax, N=16) or no injection (control, N=14). Two weeks later MDA-MB-231 BR tumor cells (250'000 cells in 0.1mL PBS) were injected into the left cardiac chamber. Four weeks later, animals were sacrificed for collection of organs and analysed histologically. Metastatic foci were significantly increased in long-tax mice (median number of foci 52, range 0–76) compared to control mice (median number of foci 20, range 0–52; p=0.015). In short-tax animals an intermediate incidence of foci was found (median 30, range 0–79), with a trend, but not a significant difference compared to untreated animals. Histologically we observed a mainly perivascular intraparenchymal infiltration pattern while superficial metastases or a spread to the cerebrospinal fluid was only rarely seen. We therefore assessed changes of the blood-brain barrier (BBB) by ultrastructural approaches. However, to date, no obvious differences in the BBB configuration after taxane treatment has been detected. In summary, our results provide evidence that taxane treatment might facilitate spread of breast cancer cells into the CNS, however underlying mechanisms remain to be determined.