Although breast cancer subtypes other than TNBC have been considered “cold tumor” unresponsive to immunotherapy, in light of the greater immunogenicity of the primary tumor and improved PCR in HR+/HER2– early breast cancer patients with anti-PD-1 drugs in the I-SPY2 trial, this suggests the potential to extend immunotherapy beyond TNBC in early breast cancer treatment, and combination paradigm with PI3K inhibition could further transform the immunosuppressive environment and enhance T-cell infiltration. This evidence concerns the gene PIK3CA and breast cancer.