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Introduction: Central nervous system metastases (mts CNS) are the most important cause of morbidity and mortality. Despite of the fact that most of these patients (pts) die within a few months, substantial subgroup may survive a year or more. We performed this study to determine factors influencing: incidence, the interval between the disease diagnosis and the mt CNS (TTPcns) and overall survival since the development of metastases in brain (OScns). Methods: We studied a cohort of 187 breast cancer pts who developed mts CNS limited to the brain and were treated at our centre from 1997 to 2007. Immunohistochemistry was performed to determine following phenotypes: 1. triple-negative, 2. triple-negative/basal-like, 3. ER+/Her-2-, 4. Her-2+/ER-, 5. Her-2+/ER+, 6. ER-/PR-/Her-2X. Results: An initial treatment started with a neurosurgery in 11%, WBRT in 87%, and followed by systemic therapy in 35,5% of pts. At the time of the mts CNS identification, 56,5% of pts had progression of the extra-cranial part of the tumor. 28 (15%) pts had developed mts CNS as the first metastatic site and 31 pts (16%) on the trastuzumab based-therapy. The incidence of monitored phenotypes was subsequent: 1. 19,4%; 2. 9,1%; 3. 21,5%; 4. 19,9%; 5. 16,7%; 6. 6,9%. Significant correlation between the phenotype and TTPcns and interval between the first distant metastatic event and the metastases in the CNS (TTPmts-cns) has been proven. In contrast to OS, the tumor phenotype had no influence on OScns. The following positive predictors relating to the prolonged OScns have been found: the number of metastatic foci in the CNS (p=0.0016); the management of local and systemic cancer treatment (p<0,0001);neurosurgery (13,8vs2,4 months, p<0.0001); systemic therapy after the effective local treatment (6,1vs1,9 months, p<0,0001); and, in the case of a further disease progression in CNS, this progression was handled by the change of the system treatment and/or by local therapy (median 10.9 vs 4.4 months, p=0.00006). The longest OScns were seen in the pts who received a dose of WBRT more than 27Gy (4,7vs2.5 months, p<0,0001). Conclusion: A comprehensive approach to patients with breast cancer and brain metastases can significantly increase OScns. This approach is based on early detection of metastases in patients with a risk tumor phenotype, intensified local treatment and systemic therapy. Supported by grant IGA Ministry of Health, CZ. No.: NR/8335-3.
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