Aspirin as a potential modality for the chemoprevention of breast cancer: A dose-response meta-analysis of cohort studies from 857,831 participants

Abstract

BackgroundPrevious meta-analyses on the relationship between aspirin use and breast cancer risk have drawn inconsistent results. In addition, the threshold effect of different doses, frequencies and durations of aspirin use in preventing breast cancer have yet to be established.ResultsThe search yielded 13 prospective cohort studies (N=857,831 participants) that reported an average of 7.6 cases/1,000 person-years of breast cancer during a follow-up period of from 4.4 to 14 years. With a random effects model, a borderline significant inverse association was observed between overall aspirin use and breast cancer risk, with a summarized RR = 0.94 (P = 0.051, 95% CI 0.87-1.01). The linear regression model was a better fit for the dose-response relationship, which displayed a potential relationship between the frequency of aspirin use and breast cancer risk (RR = 0.97, 0.95 and 0.90 for 5, 10 and 20 times/week aspirin use, respectively). It was also a better fit for the duration of aspirin use and breast cancer risk (RR = 0.86, 0.73 and 0.54 for 5, 10 and 20 years of aspirin use).MethodsWe searched MEDLINE, EMBASE and CENTRAL databases through early October 2016 for relevant prospective cohort studies of aspirin use and breast cancer risk. Meta-analysis of relative risks (RR) estimates associated with aspirin intake were presented by fixed or random effects models. The dose-response meta-analysis was performed by linear trend regression and restricted cubic spline regression.ConclusionOur study confirmed a dose-response relationship between aspirin use and breast cancer risk. For clinical prevention, long term (>5 years) consistent use (2-7 times/week) of aspirin appears to be more effective in achieving a protective effect against breast cancer.

Aspirin might reduce the incidence of breast cancer

“…Our result of overall aspirin use and breast cancer risk was different from the article reported previously, [ 9 ] which reported that a borderline significant inverse association (RR = 0.94, 95% CI: 0.87–1.01) was observed between overall aspirin use and breast cancer risk. The difference might be explained that previous study just summarized the results of cohort studies.…”

“…Our results were consistent with the previous study. Lu et al [ 9 ] confirmed that breast cancer risk decreased as aspirin intake frequency and a trend of decreasing risk for more years of aspirin intake increased. They also concluded that the optimal aspirin dose for preventing breast cancer may be in the scope of <325 mg per day, 2 to 7 times/wk, along with long-term medication (>5 years).…”

“…A meta-analysis [ 9 ] of 13 cohort studies recently published had found a borderline significant inverse association between aspirin use and breast cancer risk. The researchers had observed potential associations between aspirin intake frequency and breast cancer risk, and the duration of aspirin intake and breast cancer risk.…”

Complex roles of the old drug aspirin in cancer chemoprevention and therapy

“…Although mammary carcinogenesis is not linked to specific infection agents, studies have suggested that NSAIDs may prevent breast cancer . A recent review updates new evidence from epidemiologic and clinical studies that address the effects of aspirin in mammary tumorigenesis . A meta‐analysis of cohort studies including 857,831 participants confirms that aspirin reduces the risk of breast cancer in a dose‐dependent manner …”

S-nitrosylated and non-nitrosylated COX2 has differential expression and distinct subcellular localization in normal and breast cancer tissue

“…Data supporting pro-tumorigenic roles for COX2 include robust preclinical studies identifying COX2 as an oncogene [5][6][7][8] ; the demonstration that NSAID-based COX2 blockade inhibits cancer progression in preclinical models 9,10 ; and epidemiologic studies showing that NSAID use correlates with reductions in colon and breast cancer risk [11][12][13][14][15][16] . However, prospective clinical trials utilizing aspirin or celecoxib therapy for the prevention, recurrence and treatment of colon [17][18][19][20] or breast cancer 14,15,[21][22][23] show variable results. Further, within the breast cancer field, disparate results of COX2 immunohistochemical (IHC) studies call into question the reliability of COX2 as a breast cancer biomarker or therapeutic target [24][25][26][27][28][29] .…”