Basal-like breast cancers (BLBC) are characterized by defects in homologous recombination (HR), deficient mitotic checkpoint, and high proliferation activity. Here, we discover CIP2A as a candidate driver of BLBC. CIP2A was essential for DNA-damage-induced initiation of mouse BLBC-like mammary tumors and for survival of homologous recombination defective (HRD) BLBC cells. CIP2A was dispensable for normal mammary gland development and for unperturbed mitosis, but selectively essential for mitotic progression of DNA-damaged cells. A direct interaction between CIP2A and a DNA repair scaffold protein TopBP1 was identified and CIP2A inhibition resulted in enhanced DNA damage-induced TopBP1 and RAD51 recruitment to chromatin in mammary epithelial cells. In addition to its role in tumor initiation, and survival of BRCA-deficient cells, CIP2A also drove proliferative MYC and E2F1 signaling in basal-like triple negative breast cancer (BL-TNBC) cells. Clinically, high CIP2A expression was associated with poor patient prognosis in BL-TNBCs but not in other breast cancer subtypes. Small molecule reactivators of PP2A (SMAPs) inhibited CIP2A transcription, phenocopied the CIP2A-deficient DNA damage response (DDR), and inhibit growth of patient-derived BLBC xenograft. In summary, these results demonstrate that CIP2A directly interacts with TopBP1 and coordinates DNA-damage induced mitotic checkpoint and proliferation, thereby driving BLBC initiation and progression. SMAPs could serve as a surrogate therapeutic strategy to inhibit the oncogenic activity of CIP2A in BLBCs.