Murtola Teemu J, Visvanathan Kala, Artama Miia, Vainio Harri, Pukkala Eero
University of Tampere, School of Medicine, Tampere, Finland; Tampere University Hospital, Department of Urology, Tampere, Finland.
Johns Hopkins Bloomberg School of Public Health, Department of Epidemiology, Baltimore, Maryland, United States of America; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore Maryland, United States of America.
PLoS One. 2014 Oct 20;9(10):e110231. doi: 10.1371/journal.pone.0110231. eCollection 2014.
Recent studies have suggested that statins, an established drug group in the prevention of cardiovascular mortality, could delay or prevent breast cancer recurrence but the effect on disease-specific mortality remains unclear. We evaluated risk of breast cancer death among statin users in a population-based cohort of breast cancer patients. The study cohort included all newly diagnosed breast cancer patients in Finland during 1995-2003 (31,236 cases), identified from the Finnish Cancer Registry. Information on statin use before and after the diagnosis was obtained from a national prescription database. We used the Cox proportional hazards regression method to estimate mortality among statin users with statin use as time-dependent variable. A total of 4,151 participants had used statins. During the median follow-up of 3.25 years after the diagnosis (range 0.08-9.0 years) 6,011 participants died, of which 3,619 (60.2%) was due to breast cancer. After adjustment for age, tumor characteristics, and treatment selection, both post-diagnostic and pre-diagnostic statin use were associated with lowered risk of breast cancer death (HR 0.46, 95% CI 0.38-0.55 and HR 0.54, 95% CI 0.44-0.67, respectively). The risk decrease by post-diagnostic statin use was likely affected by healthy adherer bias; that is, the greater likelihood of dying cancer patients to discontinue statin use as the association was not clearly dose-dependent and observed already at low-dose/short-term use. The dose- and time-dependence of the survival benefit among pre-diagnostic statin users suggests a possible causal effect that should be evaluated further in a clinical trial testing statins' effect on survival in breast cancer patients.
近期研究表明，他汀类药物作为预防心血管疾病死亡的常用药物组，可能会延缓或预防乳腺癌复发，但对疾病特异性死亡率的影响仍不明确。我们在一个基于人群的乳腺癌患者队列中评估了他汀类药物使用者的乳腺癌死亡风险。该研究队列包括1995年至2003年期间芬兰所有新诊断的乳腺癌患者（31236例），这些患者来自芬兰癌症登记处。诊断前后他汀类药物使用情况的信息来自国家处方数据库。我们使用Cox比例风险回归方法，将他汀类药物使用作为时间依赖性变量，来估计他汀类药物使用者的死亡率。共有4151名参与者使用过他汀类药物。在诊断后的中位随访期3.25年（范围0.08 - 9.0年）内，6011名参与者死亡，其中3619例（60.2%）死于乳腺癌。在调整了年龄、肿瘤特征和治疗选择后，诊断后和诊断前使用他汀类药物均与降低乳腺癌死亡风险相关（风险比分别为0.46，95%置信区间0.38 - 0.55和0.54，95%置信区间0.44 - 0.67）。诊断后使用他汀类药物导致的风险降低可能受到健康依从者偏倚的影响；也就是说，癌症患者死亡时更有可能停止使用他汀类药物，因为这种关联并不明显依赖剂量，且在低剂量/短期使用时就已观察到。诊断前他汀类药物使用者生存获益的剂量和时间依赖性表明可能存在因果效应，这应在一项测试他汀类药物对乳腺癌患者生存影响的临床试验中进一步评估。
