Using a systematic in vitro approach to analyze the function of HOXA5, we found that higher levels of HOXA5 in tamoxifen-resistant MCF7 (TAMR) breast cancer cells activated the PI3K/AKT signaling pathway and resulted in reduced p53 and p21 levels and significantly reduced proportion of apoptotic cells after tamoxifen treatment. This evidence concerns the gene TP53 and breast cancer.