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激素受体(HR)阳性人表皮生长因子受体2(HER-2)阳性乳腺癌侵袭性强，易发生耐药而复发转移，目前临床多采用抗HER-2单抗联合内分泌治疗。但即使两药联合治疗，患者的预后仍不理想，这可能是HER-2下游的PI3K/Akt/mTOR信号通路激活所导致，因此HER-2受体胞外、胞内及其下游PI3K/Akt/mTOR信号通路多重抑制，及HER-2和HR的双重阻断，更有利于HR阳性HER-2阳性乳腺癌的治疗。小分子酪氨酸激酶抑制剂奈拉替尼不仅能抑制HER-1、HER-2和HER-4受体磷酸化，还可以阻断PI3K/Akt和Ras/Raf/MEK/ERK途径的下游信号传导。在强化辅助治疗研究中已证实，奈拉替尼可改善HER-2阳性乳腺癌患者的预后，尤其HR阳性HER-2阳性患者获益更加显著。在晚期乳腺癌的治疗中奈拉替尼也获得了肯定疗效，但尚缺乏奈拉替尼治疗HR阳性HER-2阳性晚期乳腺癌的相关数据。与奈拉替尼类似的小分子HER抑制剂拉帕替尼，在HR阳性HER-2阳性晚期乳腺癌患者的治疗中显示出一定疗效。鉴于奈拉替尼较拉帕替尼更优的作用机制，其有望为乳腺癌的治疗提供更多思路和选择。“,”Hormone receptor (HR), human epidermal growth factor receptor-2(HER-2) double positive breast cancer is a highly aggressive disease, and it is more susceptible to drug resistance and metastasis. Currently, although anti-HER-2 monoclonal antibody combined with endocrine therapy is commonly used in clinical practice, patients with HR-positive and HER-2-positive still have a poor prognosis. That may be caused by the activation of downstream PI3K/Akt/mTOR signaling pathway of HER-2. Therefore, simultaneously blocking the extracellular, intracellular and downstream PI3K/Akt/mTOR signaling pathway of HER-2, as well as the dual blockade of HER-2 and HR, is more conducive to the treatment of HR positive and HER-2 positive breast cancer. The small-molecule tyrosine kinase inhibitor neratinib not only inhibits the phosphorylation of HER-1, HER-2 and HER-4, but also blocks the downstream signal transduction of PI3K/Akt and Ras/Raf/MEK/ERK pathways. The intensive adjuvant chemotherapy studies has confirmed that nelatinib can improve the prognosis of patients with HER-2 positive breast cancer, especially those with HR and HER-2 double positive patients. Nelatinib has also achieved positive effect on the treatment of advanced breast cancer, but relevant data on the treatment of HR-positive and HER-2 positive advanced breast cancer are still lacking. Lapatinib, a small-molecule HER inhibitor similar to neratinib, has shown some effects on the treatment of HR-positive and HER-2 positive patients with advanced breast cancer. Given that nelatinib has a superior efficacy than lapatinib, it is expected to provide more ideas and options for the treatment strategies of breast cancer.