Abstract B6: Patterns of DNA copy number changes in primary breast cancer and brain metastases

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. Whereas colorectal cancer very seldom metastasizes to the brain (1–5%), breast cancer (15–20%) commonly metastasizes to the brain. Apparently, the brain microenvironment is specifically permissive for the growth of disseminated tumor cells from some carcinomas but not others. It is unknown by what mechanism the metastatic tumor cells adapt to the selection pressure exerted by the brain microenvironment. In this study we wanted to identify molecular breast tumor markers associated with metastatic spread to the brain. The CGH array profiles of 30 tumors from primary breast cancer patients were compared to 10 tumors of brain metastases from breast cancer cases. Copy number changes were found in all samples, and every chromosome arm (X chromosome and acrocentric short arms were excluded from the analysis). Overall, the CGH results of the primary breast tumors were in agreement with those described before. The brain metastases showed in general similar aberration patterns as the primary tumors. However, in the brain metastases a notably higher frequency of gains and losses could be found almost at every chromosome locus. Only gain of 1p and loss of 16q described as favorable markers for breast cancer were more common in the primary tumors. Statistically significant (multiarray p-value In conclusion, the results show a similarity of genetic aberration patterns between primary and metastatic tumors, i.e. the metastases carried the majority of the genetic alterations present in the corresponding primary tumors but with a significantly higher frequency. This would imply that brain metastases have occurred at a late stage of cancer progression. However, specific aberrations like gain of 2q and loss of 10q could almost exclusively be found in the metastases. Some of these markers could be useful to define a subgroup of high-risk patients and might have implications for their treatment management. Citation Information : Clin Cancer Res 2010;16(7 Suppl):B6