Antiplatelet drugs and breast cancer risk in a large nationwide Danish case-control study

Background
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.

Methods
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 each 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 2 prescriptions filled up to one 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.

Results
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 (0.86 – 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 less than 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.

Conclusion
Overall, the findings from this study do not support the use of antiplatelet drugs for breast cancer prevention.