Background/Objectives: Despite initial sensitivity to ET, most patients with HR+/HER2− breast cancer develop resistance. A key molecular mechanism of endocrine resistance in HR+ breast cancer involves dysregulation of the cyclin D–CDK4/6–Rb signaling axis, which controls the transition from the G1 to S phase of the cell cycle. Introducing cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) has changed therapeutic paradigms in HR+/HER2− breast cancer, as their synergistic use with endocrine therapy significantly prolongs progression-free survival (PFS) and effectively mitigates clinically relevant endocrine resistance in this patient population compared to ET alone. The aim of our study was to evaluate patients’ clinical characteristics, the clinical effectiveness of treatment, measured by progression-free survival (PFS), and the safety profile of combined ribociclib (CDK4/6i) and standard endocrine therapy (aromatase inhibitor) as a first-line treatment for patients with HR+/HER2− advanced or metastatic breast cancer at the Clinic of Oncology, University Clinical Centre Nis, Serbia. Methods: In this study, we present a retrospective prospective analysis of all patients with metastatic HR+/HER2− breast cancer treated with a combination of ribociclib and aromatase inhibitors in the first-line treatment of metastatic HR+/HER2− BC between June 2022 and January 2025, with a follow-up completed in October 2025. A total of 132 patients who met the criteria were included. Results: The median progression-free survival (PFS) in the entire group was 30 months, while the 12-, 24-, and 36-month PFS were 82.15%, 72.24%, and 28.75%, respectively. The overall response rate (ORR) was 41.7%, while the clinical benefit rate (CBR) was 89.3%. There was no statistically significant difference in PFS with respect to tumor grade (p= 0.54), Ki 67 level (<20% vs. >20%,p= 0.83), or the type of adjuvant endocrine therapy used (tamoxifen vs. AI) It is important to emphasize that female patients who had not previously received chemotherapy had a better response to ribociclib compared to those who had (33 m vs. 28 m,p= 0.05). Although a numerical difference in PFS was found in patients with bone-only metastases compared to those with metastases in other organs, the difference was not statistically significant (PFS 33 m vs. 30 m,p= 0.27;), and efficacy was consistent across menopausal status groups. The most common adverse effect was neutropenia, occurring in 89.4% of patients, 47.7% of whom presented with grade 3 or 4. As for hepatotoxicity, transaminase increase occurred in 25 patients (18.8%), 5 of whom (3.8%) were grade 3–4, and QTc interval prolongation occurred in 5.3% of patients. Conclusions: The results in terms of PFS and AEs are consistent with those of pivotal studies and real clinical practice data, but a direct comparison is not possible due to differences in patient populations. Ribociclib once again demonstrated efficacy in all patient subgroups and remains the gold standard, alongside ET, for first-line HR+/HER2-negative mBC.
背景/目的： 尽管激素受体阳性/人表皮生长因子受体2阴性乳腺癌患者最初对内分泌治疗敏感，但大多数会产生耐药性。HR+乳腺癌内分泌耐药的一个关键分子机制涉及细胞周期蛋白D–CDK4/6–Rb信号轴失调，该轴控制细胞周期从G1期向S期的转换。细胞周期蛋白依赖性激酶4和6抑制剂的出现改变了HR+/HER2−乳腺癌的治疗模式，因为与单用内分泌治疗相比，其与内分泌治疗的协同使用能显著延长无进展生存期，并有效缓解该患者群体中临床相关的内分泌耐药。本研究旨在评估塞尔维亚尼什大学临床中心肿瘤科HR+/HER2−晚期或转移性乳腺癌患者接受瑞波西利联合标准内分泌治疗作为一线治疗的临床特征、临床疗效（以无进展生存期衡量）及安全性。
方法： 本研究对2022年6月至2025年1月期间，在转移性HR+/HER2−乳腺癌一线治疗中接受瑞波西利联合芳香酶抑制剂治疗的所有患者进行了一项回顾性前瞻性分析，随访于2025年10月完成。共纳入132例符合标准的患者。
结果： 整个组的中位无进展生存期为30个月，而12个月、24个月和36个月的无进展生存率分别为82.15%、72.24%和28.75%。总缓解率为41.7%，临床获益率为89.3%。无进展生存期在肿瘤分级、Ki-67水平或所用辅助内分泌治疗类型方面均无统计学显著差异。需要强调的是，与既往接受过化疗的患者相比，未接受过化疗的女性患者对瑞波西利的反应更好。尽管仅骨转移患者与其他器官转移患者的无进展生存期存在数值差异，但该差异无统计学显著性，且疗效在不同绝经状态组中一致。最常见的不良反应是中性粒细胞减少症，发生率为89.4%，其中47.7%为3或4级。肝毒性方面，25例患者出现转氨酶升高，其中5例为3-4级，QTc间期延长发生率为5.3%。
结论： 在无进展生存期和不良事件方面的结果与关键研究和真实临床实践数据一致，但由于患者群体存在差异，无法直接比较。瑞波西利再次在所有患者亚组中显示出疗效，并联合内分泌治疗，仍然是HR+/HER2−转移性乳腺癌一线治疗的金标准。
肿瘤(癌症)患者之家