Use of non-steroidal anti-inflammatory drugs and risk of breast cancer: The Spanish Multi-Case-control (MCC) study

Background: The relationship between non-steroidal anti-inflammatory drug (NSAID) consumption and breast cancer has been repeatedly studied, although the results remain controversial. Most case-control studies reported that NSAID consumption protected against breast cancer, while most cohort studies did not find this effect. Most studies have dealt with NSAIDs as a whole group or with specific drugs, such aspirin, ibuprofen, or others, but not with NSAID subgroups according to the Anatomical Therapeutic Chemical Classification System; moreover, scarce attention has been paid to their effect on different tumor categories (i.e.: ductal/non-ductal, stage at diagnosis or presence of hormonal receptors). Methods: In this case-control study, we report the NSAID – breast cancer relationship in 1736 breast cancer cases and 1895 healthy controls; results are reported stratifying by the women’s characteristics (i.e.: menopausal status or body mass index category) and by tumor characteristics. Results: In our study, NSAID use was associated with a 24 % reduction in breast cancer risk (Odds ratio [OR] = 0.76; 95 % Confidence Interval [CI]: 0.64–0.89), and similar results were found for acetic acid derivatives, propionic acid derivatives and COXIBs, but not for aspirin. Similar results were found in postmenopausal and premenopausal women. NSAID consumption also protected against hormone + or HER2+ cancers, but not against triple negative breast cancers. The COX-2 selectivity showed an inverse association with breast cancer (i.e. OR < 1), except in advanced clinical stage and triple negative cancers. Conclusion: Most NSAIDs, but not aspirin, showed an inverse association against breast cancer; this effect seems to be restricted to hormone + or HER2+ cancers. Keywords: Breast cancer, Non-steroidal anti-inflammatory drug, Hormone receptor positive breast cancer, HER2 positive breast cancer, Triple negative breast cance

A 6-week, multicentre, randomised, double-blind, double-dummy, active-controlled, clinical safety study of lumiracoxib and rofecoxib in osteoarthritis patients

<p>Abstract</p> <p>Background</p> <p>Lumiracoxib is a selective cyclooxygenase-2 inhibitor effective in the treatment of osteoarthritis (OA) with a superior gastrointestinal (GI) safety profile as compared to traditional non-steroidal anti-inflammatory drugs (NSAIDs, ibuprofen and naproxen). This safety study compared the GI tolerability, the blood pressure (BP) profile and the incidence of oedema with lumiracoxib and rofecoxib in the treatment of OA. Rofecoxib was withdrawn worldwide due to an associated increased risk of CV events and lumiracoxib has been withdrawn from Australia, Canada, Europe and a few other countries following reports of suspected adverse liver reactions.</p> <p>Methods</p> <p>This randomised, double-blind study enrolled 309 patients (aged greater than or equal to 50 years) with primary OA across 51 centres in Europe. Patients were randomly allocated to receive either lumiracoxib 400 mg od (four times the recommended dose in OA) (<it>n </it>= 154) or rofecoxib 25 mg od (<it>n </it>= 155). The study was conducted for 6 weeks and assessments were performed at Weeks 3 and 6. The primary safety measures were the incidence of predefined GI adverse events (AEs) and peripheral oedema. The secondary safety measures included effect of treatment on the mean sitting systolic and diastolic blood pressure (msSBP and msDBP). Tolerability of lumiracoxib 400 mg was assessed by the incidence of AEs.</p> <p>Results</p> <p>Lumiracoxib and rofecoxib displayed similar GI safety profiles with no statistically significant difference in predefined GI AEs between the two groups (43.5% <it>vs</it>. 37.4%, respectively). The incidence and severity of individual predefined GI AEs was comparable between the two groups. The incidence of peripheral oedema was low and identical in both the groups (<it>n </it>= 9, 5.8%). Only one patient in the lumiracoxib group and three patients in the rofecoxib group had a moderate or severe event. At Week 6 there was a significantly lower msSBP and msDBP in the lumiracoxib group compared to the rofecoxib group (<it>p </it>< 0.05). A similar percentage of patients in both groups showed an improvement in target joint pain and disease activity. The tolerability profile was similar in both the treatment groups.</p> <p>Conclusion</p> <p>Lumiracoxib 400 mg od (four times the recommended dose in OA) provided a comparable GI safety profile to rofecoxib 25 mg od (therapeutic dose). However, lumiracoxib was associated with a significantly better BP profile as compared to rofecoxib.</p> <p>Trial registration number -</p> <p>NCT00637949</p

Effects of non-steroidal anti-inflammatory drugs on cancer sites other than the colon and rectum: a meta-analysis

BACKGROUND: Observational studies have consistently shown that aspirin and non-steroidal anti-inflammatory drug (NSAID) use is associated with a close to 50% reduced risk of colorectal cancer. Studies assessing the effects of NSAIDs on other cancers have shown conflicting results. Therefore, we conducted a meta-analysis to evaluate the relationship between NSAID use and cancer other than colorectal. METHODS: We performed a search in Medline (from 1966 to 2002) and identified a total of 47 articles (13 cohort and 34 case-control studies). Overall estimates of the relative risk (RR) were calculated for each cancer site using random effects models. RESULTS: Aspirin use was associated with a reduced risk of cancer of the esophagus and the stomach (RR, 0.51; 95%CI (0.38–0.69), and 0.73; 95%CI (0.63–0.84)). Use of NSAIDs was similarly associated with a lower risk of esophageal and gastric cancers (RR,0.65; 95% CI(0.46–0.92) and RR,0.54; 95%CI (0.39–0.75)). Among other cancers, only the results obtained for breast cancer were fairly consistent in showing a slight reduced risk among NSAID and aspirin users (RR, 0.77; 95%CI (0.66–0.88), and RR, 0.77; 95%CI (0.69–0.86) respectively)). CONCLUSIONS: The results of this meta-analysis show that the potential chemopreventive role of NSAIDs in colorectal cancer might be extended to other gastrointestinal cancers such as esophagus and stomach. Further research is required to evaluate the role of NSAIDs at other cancers sites

A liver fibrosis cocktail? Psoriasis, methotrexate and genetic hemochromatosis

BACKGROUND: Pathologists are often faced with the dilemma of whether to recommend continuation of methotrexate therapy for psoriasis within the context of an existing pro-fibrogenic risk factor, in this instance, patients with genetic hemochromatosis. CASE PRESENTATIONS: We describe our experience with two male psoriatic patients (A and B) on long term methotrexate therapy (cumulative dose A = 1.56 gms and B = 7.88 gms) with hetero- (A) and homozygous (B) genetic hemochromatosis. These patients liver function were monitored with routine biochemical profiling; apart from mild perivenular fibrosis in one patient (B), significant liver fibrosis was not identified in either patient with multiple interval percutaneous liver biopsies; in the latter instance this patient (B) had an additional risk factor of partiality to alcohol. CONCLUSION: We conclude that methotrexate therapy is relatively safe in patients with genetic hemochromatosis, with no other risk factor, but caution that the risk of fibrosis be monitored, preferably by non-invasive techniques, or by liver biopsy

Long-term retention on treatment with lumiracoxib 100 mg once or twice daily compared with celecoxib 200 mg once daily: A randomised controlled trial in patients with osteoarthritis

BACKGROUND: The efficacy, safety and tolerability of lumiracoxib, a novel selective cyclooxygenase-2 (COX-2) inhibitor, has been demonstrated in previous studies of patients with osteoarthritis (OA). As it is important to establish the long-term safety and efficacy of treatments for a chronic disease such as OA, the present study compared the effects of lumiracoxib at doses of 100 mg once daily (o.d.) and 100 mg twice daily (b.i.d.) with those of celecoxib 200 mg o.d. on retention on treatment over 1 year. METHODS: In this 52-week, multicentre, randomised, double-blind, parallel-group study, male and female patients (aged at least 40 years) with symptomatic primary OA of the hip, knee, hand or spine were randomised (1:2:1) to lumiracoxib 100 mg o.d. (n = 755), lumiracoxib 100 mg b.i.d. (n = 1,519) or celecoxib 200 mg o.d. (n = 758). The primary objective of the study was to demonstrate non-inferiority of lumiracoxib at either dose compared with celecoxib 200 mg o.d. with respect to the 1-year retention on treatment rate. Secondary outcome variables included OA pain in the target joint, patient's and physician's global assessments of disease activity, Short Arthritis assessment Scale (SAS) total score, rescue medication use, and safety and tolerability. RESULTS: Retention rates at 1 year were similar for the lumiracoxib 100 mg o.d., lumiracoxib 100 mg b.i.d. and celecoxib 200 mg o.d. groups (46.9% vs 47.5% vs 45.3%, respectively). It was demonstrated that retention on treatment with lumiracoxib at either dose was non-inferior to celecoxib 200 mg o.d. Similarly, Kaplan-Meier curves for the probability of premature discontinuation from the study for any reason were similar across the treatment groups. All three treatments generally yielded comparable results for the secondary efficacy variables and all treatments were well tolerated. CONCLUSION: Long-term treatment with lumiracoxib 100 mg o.d., the recommended dose for OA, was as effective and well tolerated as celecoxib 200 mg o.d. in patients with OA. TRIAL REGISTRATION: clinicaltrials.gov NCT00145301

Prescriptions for selective cyclooxygenase-2 inhibitors, non-selective non-steroidal anti-inflammatory drugs, and risk of breast cancer in a population-based case-control study

INTRODUCTION. Non-steroidal anti-inflammatory drugs (NSAIDs) prevent the growth of mammary tumours in animal models. Two population-based case-control studies suggest a reduced risk of breast cancer associated with selective cyclooxygenase-2 (sCox-2) inhibitor use, but data regarding the association between breast cancer occurrence and use of non-selective NSAIDs are conflicting. METHODS. We conducted a population-based case-control study using Danish healthcare databases to examine if use of NSAIDs, including sCox-2 inhibitors, was associated with a reduced risk of breast cancer. We included 8,195 incident breast cancer cases diagnosed in 1991 through 2006 and 81,950 population controls. RESULTS. Overall, we found no reduced breast cancer risk in ever users (>2 prescriptions) of sCox-2 inhibitors (odds ratio (OR) = 1.08, 95% confidence interval (95% CI) = 0.99, 1.18), aspirin (OR = 0.98, 95% CI = 0.90-1.07), or non-selective NSAIDs OR = 1.04, (95% CI = 0.98, 1.10)). Recent use (>2 prescriptions within two years of index date) of sCox-2 inhibitors, aspirin, or non-selective NSAIDs was likewise not associated with breast cancer risk (Ors = 1.06 (95% CI = 0.96, 1.18), 0.96 (95% CI = 0.87, 1.06) and 0.99 (95% CI = 0.85, 1.16), respectively). Risk estimates by duration (<10, 10 to 15, 15+ years) or intensity (low/medium/high) of NSAID use were also close to unity. Regardless of intensity, shorter or long-term NSAID use was not significantly associated with breast cancer risk. CONCLUSIONS. Overall, we found no compelling evidence of a reduced risk of breast cancer associated with use of sCox-2 inhibitors, aspirin, or non-selective NSAIDs.Karen Elise Jensen Foundatio

Regular use of aspirin and pancreatic cancer risk

BACKGROUND: Regular use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) has been consistently associated with reduced risk of colorectal cancer and adenoma, and there is some evidence for a protective effect for other types of cancer. As experimental studies reveal a possible role for NSAIDs is reducing the risk of pancreatic cancer, epidemiological studies examining similar associations in human populations become more important. METHODS: In this hospital-based case-control study, 194 patients with pancreatic cancer were compared to 582 age and sex-matched patients with non-neoplastic conditions to examine the association between aspirin use and risk of pancreatic cancer. All participants received medical services at the Roswell Park Cancer Institute in Buffalo, NY and completed a comprehensive epidemiologic questionnaire that included information on demographics, lifestyle factors and medical history as well as frequency and duration of aspirin use. Patients using at least one tablet per week for at least six months were classified as regular aspirin users. Unconditional logistic regression was used to compute crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Pancreatic cancer risk in aspirin users was not changed relative to non-users (adjusted OR = 1.00; 95% CI 0.72–1.39). No significant change in risk was found in relation to greater frequency or prolonged duration of use, in the total sample or in either gender. CONCLUSIONS: These data suggest that regular aspirin use may not be associated with lower risk of pancreatic cancer

Use of NSAIDs, smoking and lung cancer risk

We investigated the risk of lung cancer in relation to non-steroidal anti-inflammatory drugs (NSAIDs) among 573 cases and 857 sex- and age-matched controls for whom we had information on use of NSAIDs, from a prescription database covering all pharmacies in Denmark since 1995, and self-reported NSAID use, smoking habits and other potential confounders. Associations were expressed as odds ratios, assessed by logistic regression in unmatched analyses. After controlling for smoking habits, length of education and concomitant use of acetaminophen, we found a slightly decreased relative risk of 0.86 (95% confidence intervals, 0.65–1.14) for lung cancer associated with any use of NSAIDs. The risk decreased significantly (P=0.02) with increasing numbers of dispensed prescriptions per year during the 1–3 years before the index date with a relative risk of 0.49 (0.28–0.84) among those with four or more prescriptions per year during this period. Our findings suggest that regular use of NSAIDs is associated with a slightly or moderately reduced risk for lung cancer