We are in vestigating silicon-based platforms for detection and analysis of breast cancer cells. Attachment and spreading of MDA-MB-231 hum an m etastatic breast cancer cells was compared to that of non-tumorigenic human breast epithelial cells, MCF-10A, and the impact of SAHA (Vorinostat), a histone deacetylase (HDAC) inhibitor, on cell behaviors was ascertained. Our results showed the cancer cells attached to flat silicon and PECVD nitride-coated silicon more efficiently than non-cancer cells, and preferential cancer cell attachment was enhanced by SAHA. Fluorescent immunohistochemistry (IHC) revealed that SAHA stimulated actin stress fiber formation and focal adhesion to the substrates; atomic force microscopy (AFM) showed SAHA increased the cancer cell stiffness. Collectively, SAHA-induced biomechanical changes altered the cell morphology and mode of attachment to flat silicon and to three-dimensional silicon microstructures. This is the first report of the use of AFM to characterize the biomechanical effects of a HDAC inhibitor in cancer cells.