Per- and polyfluoroalkyl substances (PFAS) are a class of compounds commonly used as surfactants in food contact materials and household items due to their hydrophobicity. However, their physicochemical properties render them highly resistant to degradation in the environment and human body. Thus, these chemicals are environmentally ubiquitous and have been found in the serum of 98% of U.S. citizens. Evidence implicates some well characterized PFAS in breast cell carcinogenesis and cancer progression. While PFAS-induced receptor-positive breast cancer progression has been widely investigated, PFAS-induced receptor-negative breast cancer has not, and molecular mechanisms remain unclear. Additionally, Generalized Read-Across of PFAS using cancer progression endpoints are lacking. This research analyzes and compares the effects of five PFAS of increasing alkyl chain length on triple negative breast cancer progression in vitro. Using the aggressive human cell line Hs578T the effects of five PFAS were analyzed across environmentally relevant doses. Progression was assessed through 2D cell proliferation assays and “2.5D” Matrigel migration and invasion assays. Results showed significant decreases in mean number of protrusions per cell and total colony formation per well with PFBA and PFDoA treatment. Significant decreases in colony formation were observed with PFDA treatment at all doses. The mean length of the longest protrusion per cell was largely unimpacted by PFAS, except for decreases by PFDoA. When viewing the data though read-across lenses, near significant trends were seen in protrusion counts with increasing alkyl chain length at 1 nM and 10 nM PFAS. The highest alkyl length significantly decreased colony formation in a pattern seen across 10 nM, 100 nM and 1000 nM doses. Cell proliferation was not impacted by PFAS treatment. These results will help elucidate whether triple negative breast cancer progression is related to dose and alkyl chain length, and whether short-chain PFAS exhibit increased progression as longer PFAS have been shown to promote.