Inserm, Université Paris Saclay, Institut Gustave Roussy, "Exposome, Heredity, Cancer and Health" Team, Villejuif, France.
Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France.
Int J Cancer. 2023 Apr 1;152(7):1337-1347. doi: 10.1002/ijc.34343. Epub 2022 Nov 17.
Low-dose aspirin has been hypothesized to prevent cancer risk by inhibiting platelet aggregation. However, the anti-cancer effect of low-dose aspirin has recently been questioned and its effect on breast cancer development remains unclear. The impact of other antiplatelet drugs on breast cancer risk has rarely been evaluated. Thus, this study aimed to investigate the associations between breast cancer risk and antiplatelet drug use in a nationwide nested case-control study. From the Danish healthcare registries, we identified as cases all women with invasive breast cancer diagnosis between 2001 and 2018 (n = 68 852). The date of diagnosis corresponded to the index date. We matched cases to 10 population controls on age and calendar time, using risk set sampling. Controls were assigned the same index date as their matched case. We used the prescription registry to identify exposure to low-dose aspirin, clopidogrel and dipyridamole. We defined ever use of antiplatelet drugs as at least two prescriptions filled up to 1 year before the index date. We applied conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals for breast cancer associated with the use of antiplatelet drugs, overall, by breast cancer subtype and by cumulative dose. Twelve percent of women had ever been exposed to low-dose aspirin, 2% to clopidogrel and 2% to dipyridamole. In multivariable models, breast cancer risk was not associated with ever use of low-dose aspirin (OR = 1.00 [0.97-1.03]), clopidogrel (OR = 0.93 [0.87-1.00]), and dipyridamole (OR = 1.02 [0.94-1.10]), compared with never use, and there was no evidence of a dose-response relation. However, we found an inverse association between dipyridamole use and breast cancer risk among women aged <55 years old, with suggestion of a dose-response relationship (OR per 1000 Defined Daily Doses = 0.72 [0.54-0.95]). Associations did not differ by breast cancer histological type, estrogen receptor status or clinical stage at diagnosis. Overall, the findings from this study do not support the use of antiplatelet drugs for breast cancer prevention.
低剂量阿司匹林通过抑制血小板聚集被假设为预防癌症风险。然而,低剂量阿司匹林的抗癌作用最近受到质疑,其对乳腺癌发展的影响仍不清楚。很少有研究评估其他抗血小板药物对乳腺癌风险的影响。因此,本研究旨在通过一项全国性的巢式病例对照研究来调查抗血小板药物使用与乳腺癌风险之间的关系。我们从丹麦的医疗保健登记处中确定了 2001 年至 2018 年间所有患有浸润性乳腺癌的女性作为病例(n=68852)。诊断日期对应于索引日期。我们通过风险集抽样,根据年龄和日历时间与 10 名人群对照进行匹配。对照者的索引日期与匹配的病例相同。我们使用处方登记处来确定低剂量阿司匹林、氯吡格雷和双嘧达莫的暴露情况。我们将至少使用两种在索引日期前 1 年以内开的处方定义为曾经使用过抗血小板药物。我们应用条件逻辑回归来计算与使用抗血小板药物相关的乳腺癌的比值比(OR)和 95%置信区间,总体而言,根据乳腺癌亚型和累积剂量进行分析。12%的女性曾经暴露于低剂量阿司匹林,2%的女性曾经暴露于氯吡格雷,2%的女性曾经暴露于双嘧达莫。在多变量模型中,与从未使用过抗血小板药物相比,乳腺癌风险与曾经使用过低剂量阿司匹林(OR=1.00[0.97-1.03])、氯吡格雷(OR=0.93[0.87-1.00])和双嘧达莫(OR=1.02[0.94-1.10])无关,并且没有证据表明存在剂量-反应关系。然而,我们发现,在年龄<55 岁的女性中,使用双嘧达莫与乳腺癌风险之间存在反比关系,且存在剂量-反应关系(每 1000 个定义的每日剂量的 OR=0.72[0.54-0.95])。关联在乳腺癌组织学类型、雌激素受体状态或诊断时的临床分期上没有差异。总体而言,这项研究的结果不支持使用抗血小板药物预防乳腺癌。