O'Connor Thomas N, Schultz Emily, Wang Jianxin, O'Connor Tracey, Levine Ellis, Knudsen Erik S, Witkiewicz Agnieszka K
Department of Molecular and Cellular Biology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.
Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.
Cancers (Basel). 2024 Apr 30;16(9):1749. doi: 10.3390/cancers16091749.
The largest portion of breast cancer patients diagnosed after 70 years of age present with hormone receptor-positive (HR+) breast cancer subtypes. Cyclin-dependent kinase (CDK) 4/6 inhibitor treatment, in conjunction with endocrine therapy, has become standard-of-care for metastatic HR+ breast cancer. In total, 320 patients with metastatic breast cancer receiving CDK4/6 inhibitor combined with fulvestrant or an aromatase inhibitor were enrolled in an ongoing observational study or were included in an IRB-approved retrospective study. All patients receiving CDK4/6 inhibitor-based therapy that were ≥70 years of age (n = 111) displayed prolonged progression-free survival (27.6 months) as compared to patients <70 years of age (n = 209, 21.1 months, HR = 1.38, < 0.05). Specifically, patients receiving a CDK4/6 inhibitor with an aromatase inhibitor who were ≥70 years of age (n = 79) displayed exceptionally prolonged progression-free survival (46.0 months) as compared to patients receiving the same treatment who were <70 years of age (n = 161, 21.8 months, HR = 1.71, < 0.01). However, patients ≥70 years of age also experienced more frequent adverse responses to CDK4/6 inhibitor-based treatment leading to dose reduction, hold, or discontinuation than the younger cohort (69% and 53%, respectively). Treatment strategies that may decrease toxicity without affecting efficacy (such as dose titration) are worth further exploration.
70岁以后确诊的乳腺癌患者中，大部分为激素受体阳性（HR+）乳腺癌亚型。细胞周期蛋白依赖性激酶（CDK）4/6抑制剂联合内分泌治疗已成为转移性HR+乳腺癌的标准治疗方案。共有320例接受CDK4/6抑制剂联合氟维司群或芳香化酶抑制剂治疗的转移性乳腺癌患者被纳入一项正在进行的观察性研究，或被纳入一项经机构审查委员会批准的回顾性研究。与年龄小于70岁的患者（n = 209，21.1个月，HR = 1.38，P < 0.05）相比，所有接受基于CDK4/6抑制剂治疗且年龄≥70岁的患者（n = 111）均表现出无进展生存期延长（27.6个月）。具体而言，与年龄小于70岁接受相同治疗的患者（n = 161，21.8个月，HR = 1.71，P < 0.01）相比，年龄≥70岁接受CDK4/6抑制剂联合芳香化酶抑制剂治疗的患者（n = 79）表现出异常延长的无进展生存期（46.0个月）。然而，与年轻队列相比，年龄≥70岁的患者对基于CDK4/6抑制剂的治疗出现导致剂量减少、暂停或停药的不良反应也更频繁（分别为69%和53%）。可能在不影响疗效的情况下降低毒性的治疗策略（如剂量滴定）值得进一步探索。
