ASCO abstract study(mice) using TMZ to prevent brain mets from developing, treat them

[Lani]

Evaluation of temozolomide (TMZ) activity in a mouse model of brain metastases (BM) from breast cancer (BC).
Sub-category:
Metastatic Breast Cancer
Category:
Breast Cancer--Metastatic Breast Cancer
Meeting:
2008 ASCO Annual Meeting



Abstract No:
12014
Citation:
J Clin Oncol 26: 2008 (May 20 suppl; abstr 12014)
Author(s):
M. Romani, M. Cilli, C. Neumaier, G. Baio, F. Piccardi
Abstract:
Background: Cerebral metastases are observed in ~15% of BC patients within 2 years from diagnosis. Recently, there has been an increase in the incidence of BM, likely due to increased survival achieved with novel therapies. Overexpression of HER2 is a significant risk factors associated with BM that cannot be efficiently controlled by trastuzumab. The objective of this study was to develop a mouse model of BC BM, in order to evaluate the efficacy of TMZ in controlling development & growth of the metastases. Methods: We developed an in vivo model, a MCF7 BC cell line (stably transfected with a luciferase reporter vector), intracranially injected at day 0 in immunodeficient mice. There were 3 groups of mice. Group 1 (n=5) no treatment; Group 2 (n=6) was treated with oral TMZ, 150 mg/m2 body surface, day 1-7; Group 3 (n=6) the same treatment, day 8- 14. All animals were sacrificed at day 30. Tumor growth was monitored by bio imaging (Xenogen Ivis 200) and by NMR. Histopathologic analysis was performed on brain tissue that had positive tumor growth (by NMR). Results: Bio-imaging showed a dramatic difference between the light intensity of control & of treated mice. Although the signal decreased over time in all groups, the median photon flux for both groups of treated mice was considerably lower than that of the control set. The decrease in signal intensity was more evident in Group 2 as compared to Group 3, although after 3 weeks the difference between the 2 treatment arms leveled off. At the end of the observation period, the photon flux of the mice in group 2 and 3 were respectively 8.48 and 6.54 fold lower than that of the control mice. NMR imaging confirmed the tumor growth observed by bio-imaging. Conclusions: Results indicate that, with time, the majority of injected cells die and this occurs more rapidly in treated animals as compared to controls. This suggests that TMZ may accelerate the elimination of free/ micro-clusters of cells, which could correspond to micrometastases, and also appear to reduce tumor load in this mouse model of BM from BC.