Description:
Abstract Metastatic breast cancer remains essentially incurable, with mortality being especially high in patients who develop brain metastases. Approximately 15% of all epithelial tumors metastasize to the brain, with incidence rates highly dependent on the primary tumor type. Apparently, the brain microenvironment is specifically permissive for the out-growth of tumor cells from some carcinomas but not others. In a previous study we screened by array CGH primary breast tumors and brain metastases. A 10MBp loss at 11pter-p15.4 was found in 70 % of the brain metastases whereas only 15% of the early stage primary tumors showed loss of 11p. In this study the aberration pattern of 11p was verified by microsatellite analysis in primary breast tumors and brain metastases. Six markers with an average spacing of 2 MBp were analyzed at 11p15.5-p15.4. Allelic imbalance (AI) at 11p was found in 26% (11/42) of the primary tumors whereas 71.4% (15/21) of brain metastases showed AI (p=0.001). In primary tumors the occurrence of AI was associated with high grade (p=0.03) and positive lymph node status (p=0.02). Interestingly, primary tumors with a brain relapse showed an equally high AI rate (75%) as the brain metastases (71%) in contrast to primary tumors without a relapse (26%). Furthermore, two matched pairs of primary tumors and brain metastases showed equal aberrations patterns and the third matched pair showed an enlarged AI of 11p, indicating that loss of 11p is defining a specific subgroup of breast cancer patients with a high risk of brain relapse. In summary, these results indicate an accumulation of chromosomal imbalances during the carcinoma-metastasis sequence and the possible involvement of loss of 11p in brain metastasis formation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4827. doi:10.1158/1538-7445.AM2011-4827