Furthermore, breast cancer cells may also be resistant to ADC due to changes in the routes of HER2 internalization, alterations in antibody–drug ratios may affect ADC efficacy, and mutations in PIK3CA gene and loss of PTEN may disrupt PI3K/AKT/mTOR signaling pathway, decreasing the effectiveness of ADC treatment [194,195]. The gene discussed is PIK3CA; the disease is breast carcinoma.