One study demonstrated that HER2(L755S) mutations can restrict the effectiveness of trastuzumab and lapatinib treatments in individuals diagnosed with HER2-positive breast cancer[146] and are the most prevalent alterations correlated with lapatinib resistance in previously trastuzumab-treated metastatic breast cancer.[28,36]HER2 (L755S and V777L) mutations overactivate the HER3/PI3K/AKT/mTOR axis and induce endocrine resistance, conferring anti-estrogen resistance in ER-positive breast cancer.[147]. This evidence concerns the gene PIK3CA and breast carcinoma.