Department of Internal Medicine, The Catholic University of Korea Incheon St. Mary's Hospital, Incheon, Korea.
Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
Cancer Res Treat. 2021 Jan;53(1):65-76. doi: 10.4143/crt.2020.430. Epub 2020 Sep 23.
This study investigated the association of insulin, metformin, and statin use with survival and whether the association was modified by the hormone receptor status of the tumor in patients with breast cancer.
We studied 7,452 patients who had undergone surgery for breast cancer at Seoul National University Hospital from 2008 to 2015 using the nationwide claims database. Exposure was defined as a recorded prescription of each drug within 12 months before the diagnosis of breast cancer.
Patients with prior insulin or statin use were more likely to be older than 50 years at diagnosis and had a higher comorbidity index than those without it (p < 0.01 for both). The hazard ratio (HR) for death with insulin use was 5.7 (p < 0.01), and the effect was attenuated with both insulin and metformin exposure with an HR of 1.2 (p=0.60). In the subgroup analyses, a heightened risk of death with insulin was further prominent with an HR of 17.9 (p < 0.01) and was offset by co-administration of metformin with an HR of 1.3 (p=0.67) in patients with estrogen receptor (ER)-negative breast cancer. Statin use was associated with increased overall mortality only in patients with ER-positive breast cancer with HR for death of 1.5 (p=0.05).
Insulin or statin use before the diagnosis of breast cancer was associated with an increase in all-cause mortality. Subsequent analyses suggested that metformin or statin use may have been protective in patients with ER-negative disease, which warrants further studies.
本研究旨在探讨胰岛素、二甲双胍和他汀类药物的使用与生存的相关性,以及这种相关性是否受乳腺癌患者肿瘤激素受体状态的影响。
我们研究了 2008 年至 2015 年期间在首尔国立大学医院接受乳腺癌手术的 7452 名患者,使用全国性的索赔数据库。暴露被定义为在乳腺癌诊断前 12 个月内记录的每种药物的处方。
与未使用胰岛素或他汀类药物的患者相比,有胰岛素或他汀类药物使用史的患者在诊断时年龄更大,且合并症指数更高(均<0.01)。使用胰岛素的死亡风险比(HR)为 5.7(<0.01),而胰岛素和二甲双胍联合使用的效果减弱,HR 为 1.2(p=0.60)。在亚组分析中,对于雌激素受体(ER)阴性乳腺癌患者,使用胰岛素的死亡风险更高,HR 为 17.9(<0.01),而与二甲双胍联合使用可降低风险,HR 为 1.3(p=0.67)。仅在 ER 阳性乳腺癌患者中,他汀类药物的使用与全因死亡率的增加相关,死亡的 HR 为 1.5(p=0.05)。
在诊断乳腺癌之前使用胰岛素或他汀类药物与全因死亡率的增加相关。随后的分析表明,在 ER 阴性疾病患者中,二甲双胍或他汀类药物的使用可能具有保护作用,这需要进一步的研究。