Mechanically, at the upstream of Akt, PTEN elicits its phosphatase activity and inhibit the establishment of phosphatidylinositol‐3, 4, 5‐trisphosphate (PIP3) from phosphatidylinositol‐4, 5‐bisphosphate (PIP2), thus antagonizing the activity of PI3 kinase (PI3K) and leading to Akt dephosphorylation.24 In recent research, PTEN has been accepted as a target of microRNA‐221, and reported to affect the gefitinib‐resistance of cervical cancer cells.13 As for our research, we report that PTEN is crucial for microRNA‐221‐mediated breast cancer resistance to chemotherapy. Here, AKT1 is linked to breast cancer.