Division of Hematology Oncology, Department of Medicine, Geffen School of Medicine at UCLA, Santa Monica, CA 90404, United States.
Division of Hematology Oncology, Department of Medicine, Geffen School of Medicine at UCLA, Santa Monica, CA 90404, United States.
Semin Oncol. 2020 Oct;47(5):270-277. doi: 10.1053/j.seminoncol.2020.07.005. Epub 2020 Aug 29.
There are over 2 million cases a year of breast cancer, leading to over 600,000 deaths globally [1]. Despite these large numbers, increasingly more women are being cured with early stage disease and women with advanced disease are living longer [2]. The appreciation for molecular subtypes of the disease has led to significant therapeutic advances and estrogen receptor positive (ER+) breast cancer represents the largest of these subgroups. An appreciation for the importance of estrogen signaling in ER+ dates back to 1896 when Dr. George Thomas Beatson observed impressive disease responses after performing bilateral oophorectomy in 3 women at Glasgow Cancer Hospital [3]. The evolution of treatment for advanced disease from progestins, to the selective estrogen receptor modulator tamoxifen, and subsequently the aromatase inhibitors and the selective estrogen receptor degrader fulvestrant, has been accompanied by improved efficacy and decreased side effects. While the use of these drugs has changed the natural history of both early and advanced disease, it has been long recognized that many patients will develop resistance to this approach. After many years of trying to improve on single-agent endocrine treatment, since 2012 there has been an explosion of new drugs that have shown improved efficacy in combination with endocrine approaches. The first of these to receive FDA approval was the mTOR inhibitor everolimus (2012) [4], followed by the approval of 3 cyclin-dependent kinase 4 and 6 (CDK 4/6) inhibitors [palbociclib (2015) [5], ribociclib (2018) [6], and abemaciclib (2018) [7]], and more recently the PI3-kinase inhibitor alpelisib (2019) [8]. In addition, chemotherapy is still used frequently when endocrine manipulations have been exhausted. Like other incurable malignancies, the goal in advanced ER+ breast cancer is to prolong survival and maintain quality of life. Currently, we have more tools available to achieve this than ever before and we will review the efficacy and side effect data with these agents that are driving physician choices for individual patients.
每年有超过 200 万例乳腺癌病例，导致全球超过 60 万人死亡[1]。尽管数字庞大，但越来越多的早期疾病患者得到治愈，晚期疾病患者的生存期也更长[2]。对疾病分子亚型的认识提高，导致了显著的治疗进展，雌激素受体阳性（ER+）乳腺癌是最大的亚组之一。早在 1896 年，格拉斯哥癌症医院的乔治·托马斯·比塞森（George Thomas Beatson）医生在 3 名女性中进行双侧卵巢切除术时观察到令人印象深刻的疾病反应，就已经意识到雌激素信号在 ER+中的重要性[3]。晚期疾病治疗从孕激素发展到选择性雌激素受体调节剂他莫昔芬，随后是芳香化酶抑制剂和选择性雌激素受体降解剂氟维司群，疗效提高，副作用减少，这一演变过程伴随着治疗的进步。尽管这些药物的使用改变了早期和晚期疾病的自然史，但人们早就认识到，许多患者会对这种方法产生耐药性。在多年尝试改进单一内分泌治疗后，自 2012 年以来，出现了许多新的药物，这些药物与内分泌方法联合使用显示出了更好的疗效。第一个获得 FDA 批准的是 mTOR 抑制剂依维莫司（everolimus，2012 年）[4]，随后批准了 3 种细胞周期蛋白依赖性激酶 4 和 6（CDK 4/6）抑制剂[哌柏西利（palbociclib，2015 年）[5]、瑞波西利（ribociclib，2018 年）[6]和阿贝西利（abemaciclib，2018 年）[7]]，最近又批准了 PI3-激酶抑制剂阿培利司（alpelisib，2019 年）[8]。此外，当内分泌治疗无效时，仍经常使用化疗。与其他无法治愈的恶性肿瘤一样，晚期 ER+乳腺癌的目标是延长生存期并维持生活质量。目前，我们拥有比以往任何时候都多的工具来实现这一目标，我们将回顾这些药物的疗效和副作用数据，这些数据将影响医生为每位患者做出的选择。
