Can trastuzumab emtansine be replaced by additional chemotherapy plus targeted therapy for HER2-overexpressing breast cancer patients with residual disease after neoadjuvant chemotherapy?

Human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer is an aggressive phenotype with a poor prognosis, and can easily metastasize and recur. Currently, chemotherapy plus HER2-targeted therapy is the standard systemic treatment for most of these patients. Given that neoadjuvant chemotherapy (NAC) has an efficacy equivalent to that of adjuvant chemotherapy and some additional benefits, many patients, especially those with more advanced tumors, prefer NAC and generally will not receive additional chemotherapy after surgery, irrespective of the pathological response. However, achieving pathological complete response to NAC is strongly correlated with prognosis, especially in triple-negative and HER2-overexpressing breast cancer. Therefore, postoperative treatment of these patients with residual diseases should be optimized to achieve favorable outcomes. The CREATE-X study has confirmed that additional chemotherapy can improve the outcomes of patients with HER2-negative residual disease after NAC. In addition, chemotherapy plays an indispensable role in the treatment of patients who receive surgery directly or who have recurrent lesions. Therefore, can additional chemotherapy improve prognosis of patients with HER2-overexpressing residual breast cancer? At present, no studies have compared the efficacy of additional chemotherapy plus trastuzumab with that of anti-HER2 therapy alone in residual cancer. The KATHERINE study revealed that trastuzumab emtansine (T-DM1) can reduce the risk of recurrence or death by 50% compared with trastuzumab in patients with HER2-positive residual invasive breast cancer after neoadjuvant therapy. T-DM1 is an antibody-drug conjugate of trastuzumab and the cytotoxic agent emtansine, and thus, to an extent, T-DM1 is equivalent to simultaneous application of chemotherapy and targeted therapy. However, high cost and low accessibility limit its use especially in low- and middle-income countries and regions. Hence, we proposed this perspective that additional chemotherapy plus trastuzumab should be given to HER2-overexpressing breast cancer patients with residual disease after NAC to improve their prognosis by discussing that the efficacy of additional chemotherapy plus trastuzumab is superior to that of anti-HER2 therapy alone and not inferior to T-DM1. Additional chemotherapy plus trastuzumab-based HER2-targeted therapy can be used as an alternative regimen to T-DM1 when T-DM1 is unavailable. However, further clinical research on the selection of chemotherapeutic agents is warranted.