Risk of breast cancer among users of aspirin and other anti-inflammatory drugs

Abstract

We conducted a cohort study with a nested case -control analysis to evaluate the effect of anti-inflammatory drugs in breast cancer incidence using the General Practice Research Database. Women taking aspirin and paracetamol for 1 year or longer had an odds ratio (OR) of 0.77 (95 percent confidence interval (95% CI): 0.62,0.95) and 0.76 (95% CI: 0.65,0.88), respectively, compared to nonusers. Daily doses of aspirin (75 mg) and paracetamol (up to 2000 mg) showed the greatest reduced risk. Use of non-aspirin nonsteroidal anti-inflammatory drugs for more than 1 year was not associated with a reduced risk of breast cancer (OR ¼ 1.00 (95% CI: 0.84, 1.17), and the corresponding estimate among users with at least 2 years duration was similar. Our findings suggest that aspirin at cardioprophylactic doses as well as paracetamol at analgesic doses is associated with a reduced risk of breast cancer. There is mounting epidemiological evidence suggesting that nonsteroidal anti-inflammatory drugs (NSAIDs) may substantially reduce the risk of colorectal cancer (Thun et al, 1991;García Rodríguez and Huerta-Á lvarez, 2000). The effects of NSAIDs in other cancers have also been extensively studied in the last decade. Nonsteroidal anti-inflammatory drugs have been shown to prevent breast cancer in animal models (Lala et al, 1997;Robertson et al, 1998). Proposed mechanisms commonly involve the inhibition of cyclooxygenase-2 (COX-2) (Sjodahl, 2001), the enzyme responsible for the production of various prostaglandins that play a key role in the proliferation of tumour tissue; there is accumulating evidence that NSAIDs may have the ability to restore apoptosis and inhibit angiogenesis (Thun et al, 2002).Observational studies of the effect of NSAIDs in breast cancer have shown inconclusive results through a meta-analysis, including data from 15 studies that concluded that NSAIDs could be associated with a small decrease in risk (Khuder and Mutgi, 2001). However, the association between breast cancer incidence and glucocorticoid therapy has been hardly explored. Results from in vitro studies suggest that glucocorticoids have a direct inhibitory effect on proliferation of mammary cancer cells (Goya et al, 1993). However, to our knowledge, this hypothesis has not been tested in an epidemiological study.We conducted a cohort study with a nested caseÀcontrol analysis to evaluate the effect of anti-inflammatory drugs in breast cancer incidence using the General Practice Research Database (GPRD). MATERIALS AND METHODSWe used data from the GPRD. This database contains computerised information entered by general practitioners (GPs) in the UK (García Rodríguez and Pérez Gutthann, 1998). Data on over two million patients are systematically recorded and sent anonymously to the Medicines and Healthcare products Regulatory Agency (MHRA), which collects and organises this information in order to be used for research projects. The computerised information includes demographics, details from general practitioner's visits, diagnoses from specialist's re...

Use of Analgesics and Nonsteroidal Anti-inflammatory Drugs, Genetic Predisposition, and Bladder Cancer Risk in Spain

“…In our study, paracetamol was protective for bladder cancer among individuals who were GSTP1 I105V wild-type homozygous and was nonsignificantly associated to an increased risk of bladder cancer among subjects homozygous for GSTP1 minor allele. If these findings are replicated, they may suggest that GSTP1 is responsible for the inactivation of the toxic metabolite (NAPQI) of paracetamol and that the inability to eliminate this DNA adduct-forming compound may override the chemoprotective properties of paracetamol described elsewhere for bladder cancer (9,11) and breast cancer (54).…”

Clinical evidence of the relationship between aspirin and breast cancer risk (Review)

“…In this casecontrol study, the lower dose was more effective (the relative risk decreased 33%) in comparison to the higher doses, where no significant differences were obtained (aspirin RR=0.77; NSAIDs (non-aspirin) RR=1.00; acetaminophen RR=0.76). Moreover, they reported that there was no correlation between time of intake and benefit (32).…”

“…In the effort to determine an optimal dose administration of aspirin, García-Rodríguez et al studied 3,708 patients who were divided into three experimental groups according to aspirin concentration: 75, 150 or 300 mg (32). In this casecontrol study, the lower dose was more effective (the relative risk decreased 33%) in comparison to the higher doses, where no significant differences were obtained (aspirin RR=0.77; NSAIDs (non-aspirin) RR=1.00; acetaminophen RR=0.76).…”

The Role of NSAIDs in Breast Cancer Prevention and Relapse: Current Evidence and Future Perspectives

“…Results from epidemiological studies of breast cancer, however, are conflicting [9], despite many meta-analyses having indicated a chemopreventive effect of aspirin or NSAIDs against the disease [8,10,11,12,13]. In contrast, some cohort and case-control studies have reported no reduced risk of breast cancer from use of either aspirin [14,15,16,17,18,19,20,21,22] or non-aspirin NSAIDs [14,15,16,17,23,24]. …”