biostudies-literaturePeng CNIA NIH HHSNCI NIH HHS62https://www.ebi.ac.uk/biostudies/studies/S-EPMC12216965biostudies-literatureUnknown11(1)Epidemiologic data, supported by experiments, suggest aspirin may improve survival in breast cancer patients. However, recent trials reported a lack of protection, though the length of intervention was limited. Among 10,705 stages I-III breast cancer patients in the Nurses' Health Studies (NHS/NHSII), we examined the associations between post-diagnostic aspirin use and long-term breast cancer survival. During up to 34 years of follow-up, regular post-diagnostic aspirin use was associated with a 38% and 28% lower risk of breast cancer-specific and total mortality. Associations were more evident with longer duration of post-diagnostic aspirin use but attenuated with higher stage and older age at diagnosis. Pre-diagnostic long-term aspirin use was associated with the downregulation of tumor proliferation pathways in NHS/NHSII and the aspirin-gene-expression-signature predicted better survival in METABRIC. Our study highlighted the need for trials with longer duration and suggested that aspirin use before diagnosis may alter the tumor-microenvironment towards a less proliferative type.NPJ breast cancerRegular aspirin use, breast tumor characteristics and long-term breast cancer survival.PMC12216965R01 CA050385R01 CA049449P01 CA087969P01 CA87969T32 CA009001R01 CA166666U01 CA176726R01 CA067262K01AG080030U19 CA148065R01 CA50385K01 AG080030UM1 CA186107Willett WCLe PAHolmes MDRosner BASchedin PJStampfer MJBrantley KDChen WYPeng CWang THeather Eliassen AJ Heng YTamimi RMfalseRegular aspirin use, breast tumor characteristics and long-term breast cancer survival.Epidemiologic data, supported by experiments, suggest aspirin may improve survival in breast cancer patients. However, recent trials reported a lack of protection, though the length of intervention was limited. Among 10,705 stages I-III breast cancer patients in the Nurses' Health Studies (NHS/NHSII), we examined the associations between post-diagnostic aspirin use and long-term breast cancer survival. During up to 34 years of follow-up, regular post-diagnostic aspirin use was associated with a 38% and 28% lower risk of breast cancer-specific and total mortality. Associations were more evident with longer duration of post-diagnostic aspirin use but attenuated with higher stage and older age at diagnosis. Pre-diagnostic long-term aspirin use was associated with the downregulation of tumor proliferation pathways in NHS/NHSII and the aspirin-gene-expression-signature predicted better survival in METABRIC. Our study highlighted the need for trials with longer duration and suggested that aspirin use before diagnosis may alter the tumor-microenvironment towards a less proliferative type.2025-01-01T00:00:00Z2025 Jul2026-06-02T00:28:05.889Z2026-05-24T03:07:42.064ZS-EPMC122169654059561310.1038/s41523-025-00775-2