Brain Metastases in Breast Cancer - an In Vitro Study to Evaluate New Systemic Chemotherapeutic Options

Abstract

Background: Fifteen-30% of breast cancer patients develop central nervous system (CNS) metastases. The most potent drugs for the treatment of breast cancer like taxanes, anthracyclines and trastuzumab have limited efficacy for brain metastases. No standardized therapy has yet been established for this condition. Drugs with proven efficacy in the CNS and which are commonly used for primary brain tumors were applied.. We evaluated the capacity of these drugs to inhibit breast tumor cell growth in vitro. Materials and Methods: Twelve primary cell cultures of pulmonary/pleural metastases of breast cancer and 3 commercially available cell lines were used for non-radioactive cytotoxicity assays to evaluate the efficacy of 3 different concentrations of Topotecan, Cisplatin, Nimustine, Vincristine, Irinothecan, Caelyx® (pegylated liposomal Doxorubicin) and Etoposide. Results: Topotecan, Cisplatin, Caelyx® and Vincristine showed significantly higher cytostatic activity in vitro than Irinotecan, Etoposide and Nimustine. With regard to the median cytotoxicity, the order of drugs in our assays was Topotecan, Cisplatin, Vincristine, Caelyx®, Irinotecan, Etoposide and Nimustine. Nimustine showed almost no efficacy against breast cancer cells. Conclusion: Topotecan, Cisplatin, Vincristine and Caelyx® seem to be suitable candidates for further clinical evaluation. The data and the “liposomal packaging” suggest that Caelyx® might be effective in the CNS. Since pulmonary metastases are often associated with brain metastases, evaluating primary cell cultures from malignant pleural effusions could be a valuable approach for the testing of new cytostatic drugs for brain metastases.