Although survival rates among patients with breast cancer have improved in recent years, those diagnosed with advanced disease with distant metastasis face a 5-year survival rate of less than 25%, making the management of these patients an area still in significant need of continued research. Selecting the optimal treatment order from among the variety of currently available therapy options presents a relevant challenge for medical oncologists. With the understanding that the majority of patients with breast cancer and those who succumb to this disease have HR-positive disease, this review will focus on treatment options and treatment order in patients with HR-positive advanced breast cancer. While endocrine therapy is considered the preferred treatment for first-line therapy in HR-positive/HER2-negative breast cancer, selection of the specific agent depends on the menopausal status of the patient. Palbociclib, a cyclin-dependent kinase (CDK) 4/6 inhibitor, is also recommended as first-line treatment in patients with ER-positive/HER2-negative disease. In patients with endocrine therapy–resistant disease, specific strategies include sequencing of other antiestrogen receptor agents, or agents that target other molecular pathways. Future treatment strategies for patients with primary or secondary resistance to endocrine therapy for advanced disease are discussed. These strategies include first-line therapy with high-dose fulvestrant or everolimus (in combination with exemestane or letrozole or with other endocrine therapies), use of the PI3K inhibitors (e.g., buparlisib, alpelisib, pictilisib, taselisib), entinostat, CDK 4/6 inhibitors (e.g., palbociclib, ribociclib, abemaciclib), and novel selective estrogen receptor degradation agents that may enhance the targeting of acquired mutations in the ESR1 gene.

尽管近年来乳腺癌患者的存活率有所提高，但是那些诊断为患有远处转移的晚期疾病的患者的5年生存率不到25％，这使得这些患者的治疗仍然是亟需继续研究的领域。从各种当前可用的治疗选择中选择最佳治疗顺序对医学肿瘤学家提出了相关的挑战。鉴于大多数乳腺癌患者和死于这种疾病的患者均患有HR阳性疾病，因此本文将重点探讨HR阳性晚期乳腺癌患者的治疗选择和治疗顺序。虽然内分泌疗法被认为是HR阳性/ HER2阴性乳腺癌的一线治疗的首选治疗方法，具体药物的选择取决于患者的绝经状态。Palbociclib，一种细胞周期蛋白依赖性激酶（CDK）4/6抑制剂，也被推荐作为ER阳性/ HER2阴性患者的一线治疗。对于患有内分泌治疗耐药性疾病的患者，具体策略包括对其他抗雌激素受体药物或靶向其他分子途径的药物进行测序。讨论了对晚期疾病的内分泌治疗具有原发性或继发性耐药的患者的未来治疗策略。这些策略包括使用大剂量氟司韦特或依维莫司（与依西美坦或来曲唑或其他内分泌疗法联合）进行一线治疗，使用PI3K抑制剂（例如，buparlisib，alpelisib，pictilisib，taselisib），恩替司他，CDK 4 / 6种抑制剂（例如palbociclib，ESR1基因。