Minichsdorfer C, Fuereder T, Leutner M, Singer C F, Kacerovsky-Strobl S, Egle D, Greil R, Balic M, Fitzal F, Pfeiler G, Frantal S, Bartsch R, Gnant M
Department of Medicine 1, Clinical Division of Oncology, Medical University of Vienna, Vienna, Austria.
Department of Medicine 3, Clinical Division of Endocrinology, Medical University of Vienna, Vienna, Austria.
ESMO Open. 2022 Apr;7(2):100426. doi: 10.1016/j.esmoop.2022.100426. Epub 2022 Mar 22.
Statins are cholesterol-lowering drugs prescribed for the prevention and treatment of cardiovascular disease. Moreover, statins may possess anticancer properties and interact with receptor activator of nuclear factor κB ligand expression. We aimed at evaluating a hypothetical synergistic effect of statins with denosumab in early-stage breast cancer (BC) patients from the Austrian Breast and Colorectal Cancer Study Group (ABCSG) trial 18.
ABCSG-18 (NCT00556374) is a prospective, randomized, double-blind, phase III study; postmenopausal patients with hormone receptor-positive BC receiving a nonsteroidal aromatase inhibitor were randomly assigned to denosumab or placebo. In this post hoc analysis, we investigated the effects of concomitant statin therapy on recurrence risk (RR) of BC, fracture risk and bone mineral density (BMD).
In the study population (n = 3420), statin therapy (n = 824) was associated with worse disease-free survival (DFS) [hazard ratio (HR) 1.35, 95% confidence interval (CI) 1.04-1.75; P = 0.023]. While no significant effect of lipophilic statins (n = 710) on RR was observed (HR 1.30, 95% CI 0.99-1.72; P = 0.062), patients on hydrophilic statins (n = 87) had worse DFS compared with patients not receiving any statins (HR 2.00, 95% CI 1.09-3.66; P = 0.026). This finding was mainly driven by the effect of hydrophilic statins on DFS in the denosumab arm (HR 2.63, 95% CI 1.21-5.68; P = 0.014). However, this effect subsided after correction for confounders in the sensitivity analysis. No association between statin use and fracture risk or osteoporosis was observed.
According to this analysis, hydrophilic statins showed a detrimental effect on DFS in the main model, which was attenuated after correction for confounders. Our data need to be interpreted with caution due to their retrospective nature and the low number of patients receiving hydrophilic statins.
他汀类药物是用于预防和治疗心血管疾病的降胆固醇药物。此外，他汀类药物可能具有抗癌特性，并与核因子κB配体表达的受体激活剂相互作用。我们旨在评估来自奥地利乳腺癌和结直肠癌研究组（ABCSG）试验18中他汀类药物与地诺单抗对早期乳腺癌（BC）患者的假设协同效应。
ABCSG - 18（NCT00556374）是一项前瞻性、随机、双盲、III期研究；接受非甾体芳香化酶抑制剂的绝经后激素受体阳性BC患者被随机分配至地诺单抗或安慰剂组。在这项事后分析中，我们研究了他汀类药物联合治疗对BC复发风险（RR）、骨折风险和骨密度（BMD）的影响。
在研究人群（n = 3420）中，他汀类药物治疗（n = 824）与无病生存期（DFS）较差相关[风险比（HR）1.35，95%置信区间（CI）1.04 - 1.75；P = 0.023]。虽然未观察到亲脂性他汀类药物（n = 710）对RR有显著影响（HR 1.30，95% CI 0.99 - 1.72；P = 0.062），但与未接受任何他汀类药物的患者相比亲水性他汀类药物治疗的患者（n = 87）DFS较差（HR 2.00，95% CI 1.09 - 3.66；P = 0.026）。这一发现主要由亲水性他汀类药物对接受地诺单抗治疗组DFS的影响所驱动（HR 2.63，95% CI 1.21 - 5.68；P = 0.014）。然而，在敏感性分析中校正混杂因素后，这种影响减弱。未观察到他汀类药物使用与骨折风险或骨质疏松之间存在关联。
根据这项分析，亲水性他汀类药物在主要模型中对DFS显示出有害影响，在校正混杂因素后这种影响减弱。由于我们的数据具有回顾性性质且接受亲水性他汀类药物治疗的患者数量较少，因此需要谨慎解读。
