Jacobs Flavia, Gaudio Mariangela, Andreottola Chiara, Borroni Riccardo, Benvenuti Chiara, Saltalamacchia Giuseppe, Gerosa Riccardo, Canzian Jacopo, Tiberio Paola, Torrisi Rosalba, Masci Giovanna, Miggiano Chiara, Zambelli Alberto, Santoro Armando, De Sanctis Rita
Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Rozzano, MI, Italy.
Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, MI, Italy.
Oncologist. 2025 Jun 4;30(6). doi: 10.1093/oncolo/oyaf123.
CDK4/6 inhibitors (CDK4/6i) are cornerstone therapies in Hormone Receptor Positive (HR+)/Human Epidermal Growth Factor Receptor 2 Negative (HER2-) Breast Cancer (BC) and emerging evidence suggests that they may influence immune function, potentially enhancing antitumor immunity but also triggering autoimmune reactions. This study aims to investigate the prevalence of autoimmune diseases (AD) in patients with HR+/HER2- BC to identify potential predictive biomarkers and to assess the impact of AD on disease progression.
This retrospective-prospective cohort study included consecutive HR+/HER2- BC patients treated with CDK4/6i at Humanitas Research Hospital. Clinical-pathological features, treatment data, AD occurrence, and blood test values were collected. Descriptive statistics were used to determine AD prevalence, Kaplan-Meier method to estimate progression-free survival (PFS), and log-rank test to compare survival curves.
352 patients (median age: 54 years) were enrolled, of which 87.2% had metastatic disease and received palbociclib, abemaciclib, or ribociclib (45.2%, 31.0%, and 23.9%, respectively). 12.8% of patients had early BC and received abemaciclib. ADs were identified in 49 patients: most had pre-existing conditions (38 stable and 4 flaring during treatment) while 7 developed new-onset ADs. The most frequent AD were Hashimoto thyroiditis, vitiligo, and rheumatoid arthritis. In the metastatic setting, the median PFS was significantly longer in patients with AD compared to those without (P = .0013), with patients with flaring or new-onset AD showing a better PFS (P = .0015). No significant predictive biomarkers for AD evolution were found.
CDK4/6i therapy is feasible in patients with pre-existing AD. Interestingly, the onset or flaring of AD during treatment is associated with improved PFS, suggesting a potential immune activation induced by CDK4/6i. However, further robust and prospective studies are required to validate these findings and explore the underlying mechanisms.
细胞周期蛋白依赖性激酶4/6抑制剂（CDK4/6i）是激素受体阳性（HR+）/人表皮生长因子受体2阴性（HER2-）乳腺癌（BC）的基石疗法，新出现的证据表明它们可能影响免疫功能，有可能增强抗肿瘤免疫力，但也会引发自身免疫反应。本研究旨在调查HR+/HER2-BC患者自身免疫性疾病（AD）的患病率，以确定潜在的预测生物标志物，并评估AD对疾病进展的影响。
这项回顾性-前瞻性队列研究纳入了在胡马纳塔斯研究医院接受CDK4/6i治疗的连续HR+/HER2-BC患者。收集临床病理特征、治疗数据、AD发生情况和血液检测值。采用描述性统计确定AD患病率，采用Kaplan-Meier法估计无进展生存期（PFS），采用对数秩检验比较生存曲线。
共纳入352例患者（中位年龄：54岁），其中87.2%患有转移性疾病，接受了哌柏西利、阿贝西利或瑞博西利治疗（分别为45.2%、31.0%和23.9%）。12.8%的患者患有早期BC，接受了阿贝西利治疗。49例患者被确诊患有AD：大多数患者有既往疾病（38例在治疗期间病情稳定，4例病情加重），而7例出现新发AD。最常见的AD是桥本甲状腺炎、白癜风和类风湿性关节炎。在转移性疾病患者中，患有AD的患者的中位PFS明显长于未患AD的患者（P = 0.0013），病情加重或新发AD的患者的PFS更好（P = 0.0015）。未发现AD演变的显著预测生物标志物。
CDK4/6i疗法在患有既往AD的患者中是可行的。有趣的是，治疗期间AD的发作或加重与PFS改善相关，提示CDK4/6i可能诱导了潜在的免疫激活。然而，需要进一步进行有力的前瞻性研究来验证这些发现并探索潜在机制。
