Most importantly, our study suggests that HER2 mutations in patients with HER2-amplified BC may contribute to resistance to anti-HER2-directed therapy with chemotherapies, even though only low frequencies of the mutations were found (Table 2), which imply HER2 mutation could be one of the predictive markers of HER2 directed therapy and new resistance mechanism of HER2 pathway in breast cancer. Here, ERBB2 is linked to breast carcinoma.