他汀类是常用的降低血脂药物，可以降低人体胆固醇水平，而人体可以利用胆固醇合成孕激素、雄激素，再通过芳香酶合成雌激素。芳香酶抑制剂可以减少雌激素受体阳性乳腺癌患者的雌激素水平，如果胆固醇水平过高，芳香酶抑制剂不足以减少雌激素的合成，可能造成乳腺癌复发。
2020年6月22日，施普林格自然旗下《乳腺癌研究与治疗》在线发表丹麦奥胡斯大学、奥胡斯大学医院、南丹麦大学、美国佛蒙特大学、瑞典隆德大学的研究报告，针对丹麦全国乳腺癌术后芳香酶抑制剂辅助治疗绝经患者人群，检验了他汀类对乳腺癌复发风险的影响。
该全国人口队列研究根据丹麦乳腺癌协作组数据库和丹麦癌症登记数据库，对2007～2017年丹麦全国诊断为I～III期雌激素受体阳性乳腺癌术后芳香酶抑制剂辅助治疗的1万4773例绝经患者进行回顾分析。根据丹麦全国处方登记数据库，确定其中乳腺癌诊断后至少处方过1次他汀类的患者，并按处方后6个月他汀类用药时间变化建立模型。从乳腺癌诊断后7个月开始随访，直至首次复发、死亡、移民、满5年或2018年9月25日为止。推算5年复发比例，通过多因素比例风险回归模型对其他影响因素进行校正后，对他汀类用药与未用药进行比较，计算校正后复发风险比及其95%置信区间。
结果，随访5年期间，乳腺癌复发比例：
服用他汀类：10.12‰（95%置信区间：6.92～14.28）
未用他汀类：13.40‰（95%置信区间：12.36～14.51）
根据多因素模型分析，对其他影响因素进行校正后，服用与未用他汀类的患者相比，5年乳腺癌复发比例低28%（校正后风险比：0.72，95%置信区间：0.50～1.04）。
此外，如果仅对亲脂性他汀类进行比较，服用与未用他汀类的患者相比，5年乳腺癌复发比例低30%（校正后风险比：0.70，95%置信区间：0.48～1.02）。
因此，该研究结果表明，对于早期乳腺癌术后芳香酶抑制剂辅助治疗的绝经患者，服用与未用他汀类降脂药相比，乳腺癌复发风险总体较低。
Breast Cancer Res Treat. 2020 Jun 22. Online ahead of print.
Statin use and breast cancer recurrence in postmenopausal women treated with adjuvant aromatase inhibitors: a Danish population-based cohort study.
Sixten Harborg, Uffe Heide-Jorgensen, Thomas P. Ahern, Marianne Ewertz, Deirdre Cronin-Fenton, Signe Borgquist.
Aarhus University Hospital, Aarhus, Denmark; Aarhus University, Aarhus, Denmark; University of Vermont, Burlington, USA; University of Southern Denmark, Odense, Denmark; Lund University, Lund, Sweden.
PURPOSE: To examine the association between statin use and risk of breast cancer recurrence in a national Danish cohort of postmenopausal breast cancer patients receiving aromatase inhibitors (AI) in the adjuvant setting.
PATIENTS AND METHODS: We enrolled all postmenopausal patients diagnosed with stage I-III estrogen receptor positive breast cancer during the years 2007-2017, assigned adjuvant AI treatment, and registered in both the Danish Breast Cancer Group database and the Danish Cancer Registry. We ascertained incident statin exposure (≥1 prescription post-diagnosis) from the Danish National Prescription Registry and modeled statins as a time-varying exposure lagged by 6 months. Follow-up began 7 months after diagnosis and continued to the first event of recurrence, death, emigration, 5 years elapsed, or 25th September 2018. We estimated incidence rates of recurrence at 5 years and used Cox regression models to compute crude and adjusted hazard ratios (HRs) with 95% confidence intervals (95% CI), comparing statin exposure with non-exposure.
RESULTS: We enrolled 14,773 eligible patients. During the 5 years of follow-up, there were 32 recurrences in 3163 person-years of follow-up among statin-exposed patients, and 612 recurrences in 45,655 person-years among unexposed patients (incidence rate per 1000 person-years: 10.12 [95% CI 6.92-14.28] and 13.40 [95% CI 12.36-14.51], respectively). In multivariable models, any statin exposure was associated with a reduced rate of 5-year breast cancer recurrence (adjusted HR 0.72 [95% CI 0.50-1.04]). Considering only lipophilic statins as exposure the results were similar (adjusted HR 0.70 [95% CI 0.48-1.02]).
CONCLUSIONS: Statin use was associated with a reduced risk of breast cancer recurrence among postmenopausal patients diagnosed with early stage breast cancer who received adjuvant AI therapy.
KEYWORD: Aromatase inhibitors, Cohort study, Endocrine therapy, Statins, Breast cancer
DOI: 10.1007/s10549-020-05749-5
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