Improved prognostication and management of Invasive Breast Cancer (IBC) requires more precise knowledge of the molecular pathways that lead to the development and progression of cancer. Thus, we aimed to identify potential candidate genes in Estrogen Receptor-positive (ER+) and Progesterone Receptor-negative (PR-) IBC to clarify the molecular mechanisms underlying this subtype of breast cancer. A retrospective invasive breast cancer cohort was utilized in this study. An integrated bioinformatic approach was developed to assess the associations between clinical outcomes and data obtained from the Cancer Genome Atlas (TCGA). Differentially Expressed Genes (DEGs) were identified using MultiExperiment Viewer. Multiple online tools were employed to conduct functional enrichment analysis. STRING was used to create protein-protein interaction networks for the identified DEGs. The Breast Cancer Gene Miner online database was employed to analyze the associations of key hub genes with tumor features and clinical outcomes. Overall, 33 and 88 genes were found to be upregulated and downregulated, respectively, in ER+PR- IBC. The upregulated genes are mainly associated with cell proliferation, cell division, mitosis, cell-cell adhesions, and autophagy; the downregulated genes are implicated in lymphocyte migration and negative regulation of immune system processes. Analysis of the protein-protein interaction networks and gene-gene co-occurrence identified the upregulated hub genes PIP4K2C, CDH1, and CLTC are closely related to key nodes. High PIP4K2C, CDH1, and CLTC expression were associated with more aggressive tumor features (p<0.05) and high PIP4K2C and CDH1 expression were associated with poorer disease-free survival (p<0.05). Overall, the study highlights key molecular biomarkers and mechanisms that could be targeted to improve the treatment of ER+PR- IBC.