Factors influencing survival in patients with breast cancer and single or solitary brain metastasis.

AIM: To perform a comprehensive analysis of patients with breast cancer and solitary or single brain metastasis and to analyze factors influencing survival from brain metastasis. METHODS: One hundred consecutive patients with single or solitary brain metastasis were treated in one institution in the years 2003-2009. Brain lesions were diagnosed by magnetic resonance imaging (MRI). A total of 57% of patients underwent resection of brain metastasis, 95% of patients received whole-brain radiation therapy (WBRT) and 67% were treated systemically after WBRT. RESULTS: Median survival from the detection of brain metastasis was 13 months and 28% of patients survived for 2 years. In 29 patients with solitary brain metastasis, median survival was 20 months (2-80 months) and in 71 patients with single brain metastasis it was 11 months (1-79 months) p = 0.01. Median survival from brain metastasis in patients with Recursive Partitioning Analysis Radiation Therapy Oncology Group (RPA RTOG) prognostic class I, II and III was 22 months (4-80 months), 13 months (2-79 months) and 6 months (0.4-28 months), respectively, p < 0.0001. Median survival from brain metastasis in triple-negative, HER2, luminal B and luminal A subtypes was 11 months, 13 months, 16 months and 15 months, respectively (p = 0.60). Multivariate analysis revealed that RPA RTOG prognostic class I, neurosurgery and systemic therapy after WBRT were factors that correlated with survival. CONCLUSIONS: In patients with one metastatic lesion in the brain, affiliation to RPA RTOG prognostic class I and intensive local and systemic treatment had a strong correlation with survival. There was no significant correlation between biological subtype of cancer and survival.

Breast cancer brain metastases: differences in survival depending on biological subtype, RPA RTOG prognostic class and systemic treatment after whole-brain radiotherapy (WBRT).

BACKGROUND: Patients with breast cancer brain metastasis are a heterogeneous group in relation to tumor biology and outcome. MATERIALS AND METHODS: The group of 222 breast cancer patients with brain metastasis was divided into three biological subgroups. The propensity of biological subtypes for metastases to the brain and survivals depending on biological subtype, recursive partitioning analysis of Radiation Therapy Oncology Group (RPA RTOG) prognostic class and the use of systemic treatment after whole-brain radiotherapy were assessed. RESULTS: The rate of patients with triple-negative, human epidermal growth factor receptor 2 (HER2)-positive and luminal breast cancer with brain metastases was 28%, 53% and 19%, respectively. Median survival from brain metastases in triple-negative, HER2-positive and luminal subtype was 3.7, 9 and 15 months, respectively. Median survival from brain metastases in RPA RTOG prognostic class I, II and III was 15, 11 and 3 months, respectively. In the luminal and in the triple-negative subtype, systemic therapy prolonged survival from 3 to 14 months and from 3 to 4 months, respectively. In HER2-positive subtype, median survival without further treatment, after chemotherapy and after chemotherapy with targeted therapy were 3, 8 and 11 months, respectively. CONCLUSIONS: HER2-positive and triple-negative breast cancers have special predilection for metastases to the brain. Survival from brain metastases depended on performance status and the use of systemic treatment.

Differential kinetics of various subsets of thymic bone marrow-derived stromal cells in rat chimeras.

Identification of those cells within the thymic stroma which are responsible for tolerance induction remains controversial. Evidence derived from studies of bone marrow chimeras or thymus transplants attributed this function to cells of haematopoietic origin, usually class II positive medullary dendritic cells (DC). Recent data suggest, however, that a stromal element located in the thymus cortex might be involved in negative selection. To further explore this issue we used immunohistology and immunocytology with a combination of allotype and cell type specific monoclonal antibodies (MoAb) to study the turnover of thymic stromal cells of haematopoietic origin in different rat models of allogeneic and congenic bone marrow (BM) radiation chimeras. Use of CFU-GM cultured BM inoculum for congenic recipients allowed us to distinguish between direct homing of donor myeloid cells and the delayed migration of the donor stem cell progeny after the post-irradiation recovery of the recipient. Our data indicate a heterogeneity in the turnover rate of thymic mobile stromal cells. While DC and a subset of macrophages located in the cortex as well as in the medulla (ED1+), within 4 weeks were virtually all of donor type, cortical macrophages detected by ED2 MoAbs were still incompletely replaced after a period as long as 20 weeks. Slow turnover, location and variable class II expression may imply a role for thymic cortical macrophages in (self-) tolerance induction.

Kinetics of thymocyte regeneration in adult adriamycin treated rats: evidence for an exclusive role of bone marrow derived cells.

This paper describes a new, less toxic and more selective approach to study the adult thymus. An adriamycin (ADR), sparing bone marrow (BM) stem cells and nontoxic to cells that are not in cycle during treatment, was used as a depleting agent in conjunction with vascular thymus transplantation. We were able to deplete the thymus of thymocytes without damaging its microenvironment as witnessed by intact antigen profiles of stromal cells. Two models were used in this study, (1) regeneration after ADR induced depletion with or without BM reconstitution either systemically or intrathymically and (2) thymocyte turnover or regeneration in vascularly transplanted thymi. In the latter model either normal thymus was grafted into ADR treated recipient or ADR depleted thymus was grafted into normal recipient. These experiments clearly show that intact BM function is a prerequisite for intact continued cellularity of the adult thymus. Although the resident thymocyte population possesses some limited proliferating potential, it clearly does not seem to have a permanent self-renewing capacity of intrathymic stem cells.