tretinoin and Carcinoma--Lobular

There are strong data showing that increased breast cancer risk is associated with increased mammographic density. Tamoxifen has been shown to decrease the risk of invasive breast cancer and decrease breast density. We sought to demonstrate and calculate the extent of change in mammographic density in women who have taken tamoxifen for up to 2 years. We evaluated mammograms from 28 high-risk women who were taking tamoxifen. Four different methods of evaluation were used: (a) two qualitative methods (Wolfe criteria and the American College of Radiology Breast Imaging and Reporting Data System criteria); (b) one semiquantitative method (mammograms were assigned one of five semiquantitative scores by visual inspection); and (c) one quantitative method (computer-aided calculation of fibroglandular area from digitized mammograms). The Wolfe criteria showed a 0.03 category decrease per year (P = 0.50). The American College of Radiology Breast Imaging and Reporting Data System criteria showed a 0.1 category decrease per year (P = 0.12). Semiquantitative criteria showed a 0.2 category decrease per year (P = 0.039). Digitized scores showed a 4.3% decrease per year (P = 0.0007). In conclusion, tamoxifen causes a decrease in mammographic density with use, an effect that is better quantitated with semiquantitative criteria or digitized images. Density change might become useful as a surrogate end point for the effect of tamoxifen and other chemopreventive measures, although our data do not predict an individual's degree of risk reduction.

Topics: Adult; Age Factors; Aged; Anticarcinogenic Agents; Antineoplastic Agents; Biomarkers, Tumor; Breast; Breast Neoplasms; Carcinoma in Situ; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Feasibility Studies; Female; Humans; Mammography; Middle Aged; Pilot Projects; Postmenopause; Radiographic Image Enhancement; Reproducibility of Results; Selective Estrogen Receptor Modulators; Tamoxifen; Tretinoin

Dendritic cells (DCs) are antigen-presenting cells that are currently employed in cancer clinical trials. However, it is not clear whether their ability to induce tumour-specific immune responses when they are isolated from cancer patients is reduced relative to their ability in vivo. We determined the phenotype and functional activity of DCs from cancer patients and investigated the effect of putrescine, a polyamine molecule that is released in large amounts by cancer cells and has been implicated in metastatic invasion, on DCs.. The IL-4/GM-CSF (granulocyte-macrophage colony-stimulating factor) procedure for culturing blood monocyte-derived DCs was applied to cells from healthy donors and patients (17 with breast, 7 with colorectal and 10 with renal cell carcinoma). The same peroxide-treated tumour cells (M74 cell line) were used for DC pulsing. We investigated the effects of stimulation of autologous lymphocytes by DCs pulsed with treated tumour cells (DC-Tu), and cytolytic activity of T cells was determined in the same target cells.. Certain differences were observed between donors and breast cancer patients. The yield of DCs was dramatically weaker, and expression of MHC class II was lower and the percentage of HLA-DR-Lin- cells higher in patients. Whatever combination of maturating agents was used, expression of markers of mature DCs was significantly lower in patients. Also, DCs from patients exhibited reduced ability to stimulate cytotoxic T lymphocytes. After DC-Tu stimulation, specific cytolytic activity was enhanced by up to 40% when DCs were from donors but only up to 10% when they were from patients. IFN-gamma production was repeatedly found to be enhanced in donors but not in patients. By adding putrescine to DCs from donors, it was possible to enhance the HLA-DR-Lin- cell percentage and to reduce the final cytolytic activity of lymphocytes after DC-Tu stimulation, mimicking defective DC function. These putrescine-induced deficiencies were reversed by treating DCs with all-trans retinoic acid.. These data are consistent with blockade of antigen-presenting cells at an early stage of differentiation in patients with breast cancer. Putrescine released in the microenvironmement of DCs could be involved in this blockade. Use of all-trans retinoic acid treatment to reverse this blockade and favour ex vivo expansion of antigen-specific T lymphocytes is of real interest.

Topics: Aged; Antineoplastic Agents; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Intraductal, Noninfiltrating; Carcinoma, Lobular; Carcinoma, Renal Cell; Cell Transformation, Neoplastic; Colorectal Neoplasms; Dendritic Cells; Female; Humans; Kidney Neoplasms; Middle Aged; Phenotype; Putrescine; T-Lymphocytes; Tretinoin