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Summary:We have evaluated whether allogeneic hematopoietic stem cell transplantation (HSCT) could induce an antitumor effect in patients with metastatic solid tumors. A total of 12 HLA-identical siblings and 6 HLA-A-, -B-and -DRb1-compatible unrelated grafts were used. Diagnoses were adenocarcinoma of kidney (n ¼ 10), colon (n ¼ 6), breast (n ¼ 1) and cholangiocarcinoma (n ¼ 1). Conditioning was fludarabine 30 mg/m 2 /day for 3 days and 2 Gy of total body irradiation. Recipients of unrelated HSCT were also given thymoglobuline and two additional days of fludarabine. The median CD34+ cell dose was 7.5 Â 10 6 / kg. Immunosuppression was mycophenolate mofetil and cyclosporin. Among all, 12 patients became complete donor chimeras within a median of 28, 29 and 65 days for B, myeloid and T cells, respectively. Two patients rejected the grafts, one developed marrow aplasia and three were mixed chimeras. The probability of grades II-IV acute graft-versus-host-disease (GVHD) was 57%. Regression of all tumor metastases was seen in one patient with colon carcinoma. Another patient with colon and two with renal carcinoma had regression of lung metastases, but progression of metastases in the liver and/or bone. Necrosis of lung metastasis was found in one further patient with renal carcinoma who died of graft-versushost-disease (GVHD). In all, 10 patients died; four of transplant-related complications, one of trauma and five of progressive disease. Thus, progression was common after allogeneic HSCT in unselected patients with advanced solid tumors. However, the regression of some metastases associated with GVHD provides suggestive evidence that the GVHD effect may occur in renal and colon adenocarcinoma using reduced intensity conditioning. The immune system is known to induce tumor regression. 1 Following allogeneic hematopoietic stem cell transplantation (HSCT), graft-versus-host disease (GVHD) has been found to contribute to an antileukemic effect. 2,3 An alloresponse of donor T lymphocytes is most probably the cause of GVHD and the graft-versus-leukemia (GVL) effect. 4 An allogeneic graft-versus-tumor (GVT) effect has also been reported in breast and renal metastatic carcinoma. [5][6][7][8][9] When performing HSCT, lethal myeloablative conditioning to eradicate leukemia and induce marked immunosuppression to pave the way for the donor immunohematopoietic system has been the routine for several decades 10À13 . However, this approach has been challenged by using lower doses and less toxic conditioning to induce immunosuppression and take advantage of the GVT effect later rather than the antitumor effect of chemoradiotherapy. [14][15][16][17][18][19]

An enhanced understanding of the biology of breast cancer metastases is needed to individualize patient management. Here, we show that tumor characteristics of breast cancer metastases significantly influence post-relapse survival, emphasizing that molecular investigation at relapse offers clinically relevant information, with the potential to improve patient management and survival.

The addition of oral capecitabine to docetaxel improves response rate, time to progression (TTP) and overall survival in anthracycline-pretreated metastatic breast cancer (MBC). This phase II study evaluates the efficacy and safety of a 21-day cycle of oral capecitabine (1000 mg m À2 twice daily, days 1 -14) plus i.v. paclitaxel (175 mg m À2 , day 1) in anthracycline-pretreated advanced/ MBC. In all, 73 patients were enrolled at 13 Swedish and Spanish centres. The objective response rate was 52% (95% confidence interval (CI): 40 -63%) in the intent-to-treat population, including complete responses in 11%. Disease was stabilised in a further 29%. The median time to disease progression (TTP) was 8.1 months and the median overall survival was 16.5 months. The combination was generally well tolerated with a predictable safety profile. The most common treatment-related nonhaematological adverse events were hand -foot syndrome (42%), alopecia (30%) and diarrhoea (26%). The only treatment-related Grade 3/4 adverse events occurring in 45% of patients were alopecia (22%) and hand -foot syndrome (11%). Grade 3/4 neutropenia and lymphocytopenia were reported in 12 and 14% of patients, respectively. Capecitabine plus paclitaxel is highly active with a favourable safety profile in anthracycline-pretreated MBC.

in collaboration with the TEX study group Abstract Purpose: The complete molecular basis of the organ-specificity of metastasis is elusive. This study aimed to provide an independent characterization of the transcriptional landscape of breast cancer metastases with the specific objective to identify liver metastasis-selective genes of prognostic importance following primary tumor diagnosis.Experimental Design: A cohort of 304 women with advanced breast cancer was studied. Associations between the site of recurrence and clinicopathologic features were investigated. Fine-needle aspirates of metastases (n ¼ 91) were subjected to whole-genome transcriptional profiling. Liver metastasis-selective genes were identified by significance analysis of microarray (SAM) analyses and independently validated in external datasets. Finally, the prognostic relevance of the liver metastasis-selective genes in primary breast cancer was tested.Results: Liver relapse was associated with estrogen receptor (ER) expression (P ¼ 0.002), luminal B subtype (P ¼ 0.01), and was prognostic for an inferior postrelapse survival (P ¼ 0.01). The major variation in the transcriptional landscape of metastases was also associated with ER expression and molecular subtype. However, liver metastases displayed unique transcriptional fingerprints, characterized by downregulation of extracellular matrix (i.e., stromal) genes. Importantly, we identified a 17-gene liver metastasis-selective signature, which was significantly and independently prognostic for shorter relapse-free (P < 0.001) and overall (P ¼ 0.001) survival in ER-positive tumors. Remarkably, this signature remained independently prognostic for shorter relapse-free survival (P ¼ 0.001) among luminal A tumors.Conclusions: Extracellular matrix (stromal) genes can be used to partition breast cancer by site of relapse and may be used to further refine prognostication in ER positive primary breast cancer.