Aspirin and other nonsteroidal anti-inflammatory drugs and breast cancer incidence in a large U.S. cohort.

Use of nonsteroidal anti-inflammatory drugs (NSAIDs), particularly aspirin, has consistently been associated with reduced risk of breast cancer in case-control studies. However, results from prospective studies have been less consistent. We examined the association between NSAID use and breast cancer incidence, adjusting for multiple breast cancer risk factors among 77,413 women in the Cancer Prevention Study II Nutrition Cohort. During follow-up from 1992 to 2001, we observed 3,008 cases of incident breast cancer. Information on NSAID use was obtained from a questionnaire completed at enrollment in 1992 or 1993 and was updated using follow-up questionnaires in 1997 and 1999. NSAID use was modeled using time-dependent variables to update exposure status. Neither current total NSAID use (aspirin and other NSAIDs combined) nor current aspirin use were associated with breast cancer incidence even at relatively high levels of use [rate ratio (RR), 1.07; 95% confidence interval (95% CI), 0.96-1.21 for > or =60 NSAID pills per month compared with no reported use of NSAIDs; RR, 1.01; 95% CI, 0.84-1.20 for > or =60 aspirin per month compared with no reported use of aspirin]. Even long-duration regular use (> or =30 pills per month for > or =5 years) was not associated with breast cancer incidence (RR, 1.05; 95% CI, 0.88-1.26 for total NSAIDs; RR, 0.88; 95% CI, 0.69-1.12 for aspirin). Although we cannot exclude a small reduction in breast cancer risk associated with NSAID use, the results of this study provide evidence against a large reduction in risk.     

Non-steroidal anti-inflammatory drug use and risk of adult leukemia.

Epidemiological studies have suggested that regular use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) may be associated with reduced risk of some types of malignancy. Leukemia incidence and self-reported aspirin, as well as other NSAID use, was examined in a prospective cohort of >28,000 postmenopausal women. Eighty-one incident leukemia cases occurred during the period 1993-2000. The multivariate-adjusted relative risk of leukemia was 0.45 (95% confidence interval: 0.27-0.75) for women who reported using aspirin two or more times per week compared with women who reported no use. Similar inverse associations were observed for the two subtypes of leukemia analyzed. In contrast, for women who reported using nonaspirin NSAIDs, the multivariate-adjusted relative risk of leukemia was 1.31 (95% confidence interval: 0.77-2.22). Analyses that excluded cases diagnosed before 1995 did not notably alter results. To our knowledge, this is the first prospective study to examine the association between NSAID use and incident adult leukemia. Although preliminary, the notable differences observed in leukemia risk between aspirin and nonaspirin NSAID use warrant further investigation.     

Aspirin and nonsteroidal anti-inflammatory drug use and risk of pancreatic cancer: a meta-analysis.

BACKGROUND: The association between use of nonsteroidal anti-inflammatory drugs (NSAID), including aspirin, and risk of pancreatic cancer is controversial. We did a meta-analysis to summarize available evidence from epidemiologic studies investigating the relation between use of aspirin or other NSAIDs and the risk of pancreatic cancer. METHODS: We identified potential studies by searching the MEDLINE database (from 1966 to October 2006) and by reviewing the reference lists of pertinent publications. Studies were eligible for inclusion if they met the following criteria: (a) had a case-control or prospective design, (b) examined exposure to aspirin or NSAIDs, (c) the outcome was pancreatic cancer incidence or mortality, and (d) they provided a relative risk (RR) estimate with corresponding confidence interval or sufficient information to permit their calculation. Study-specific RR estimates were pooled using a random effects model. RESULTS: A total of 11 studies (3 case-control studies, 7 cohort studies, and 1 randomized trial), involving 6,386 pancreatic cancer cases, was included in the meta-analysis. The summary RR estimate did not indicate any association between aspirin/NSAID use and risk of pancreatic cancer [any/regular use versus nonregular/never use: RR, 1.01; 95% confidence interval (95% CI), 0.91-1.11; P(heterogeneity) = 0.09]. Neither use of aspirin, nonaspirin NSAIDs, nor overall NSAIDs were associated with pancreatic cancer risk. There was also no overall association with frequent (six or more tablets/times per week versus none: RR, 0.86; 95% CI, 0.61-1.23) or long-term (>or=20 years) use of aspirin (RR, 1.21; 95% CI, 0.74-1.96). CONCLUSIONS: Current epidemiologic evidence does not indicate that use of aspirin or NSAIDs is associated with the risk of pancreatic cancer.     

Aspirin, NSAID, and acetaminophen use and the risk of endometrial cancer

To date, no prospective studies have explored the relationship between the use of aspirin, other nonsteroidal anti-inflammatory medications (NSAID), and acetaminophen and endometrial adenocarcinoma. Of the 82,971 women enrolled in a prospective cohort study, 747 developed medical record-confirmed invasive endometrial cancer over a 24-year period. Use of aspirin was ascertained from 1980 to 2004, and for other NSAIDs and acetaminophen, from 1990 to 2004. Cox regression models calculated multivariate relative risks (MV RR), controlling for body mass index (BMI), postmenopausal hormone (PMH) use, and other endometrial cancer risk factors. Currency, duration, and quantity of aspirin were not associated with endometrial cancer risk overall [current use: MV RR, 1.03; 95% confidence interval (CI) 0.83-1.27; >10 years of use: MV RR, 1.01; 95% CI, 0.78-1.30; and cumulative average >7 tablets per week: (MV RR, 1.10; 95% CI, 0.84-1.44)]. However, stratified analyses showed that a lower risk of endometrial cancer among obese (BMI, >or=30 kg/m(2)) women was seen with current aspirin use (MV RR, 0.66; 95% CI, 0.46-0.95). The greatest risk reduction for current aspirin users was seen in postmenopausal obese women who had never used PMH (MV RR, 0.43; 95% CI, 0.26-0.73). The use of other NSAIDs or acetaminophen was not associated with endometrial cancer. Our data suggest that use of aspirin or other NSAIDs does not play an important role in endometrial cancer risk overall. However, risk was significantly lower for current aspirin users who were obese or who were postmenopausal and had never used PMHs; these subgroup findings require further confirmation.     

Breast cancer and nonsteroidal anti-inflammatory drugs: prospective results from the Women's Health Initiative

We analyzed data from the prospective Women's Health Initiative (WHI) Observational Study to examine the effects of regular use of aspirin, ibuprofen, and other nonsteroidal anti-inflammatory drugs (NSAIDs) on breast cancer risk. We studied a population of 80,741 postmenopausal women between 50 and 79 years of age who reported no history of breast cancer or other cancers (excluding nonmelanoma skin cancer), and we completed a personal baseline interview that elicited comprehensive health information including data on breast cancer risk factors and NSAID use. All of the cases were adjudicated by WHI physicians using pathology reports. Our analysis was based on 1392 confirmed cases of breast cancer. Relative risks (RRs) with 95% confidence intervals (CIs) were estimated with adjustment for age and other breast cancer risk factors. Regular NSAID use (two or more tablets/week) for 5-9 years produced a 21% reduction in the incidence of breast cancer (RR, 0.79; 95% CI, 0.60-1.04); regular NSAID use for 10 or more years produced a 28% reduction (RR, 0.72; CI, 0.56-0.91), and there was a statistically significant inverse linear trend of breast cancer incidence with the duration of NSAID use (P < 0.01). The estimated risk reduction for long-term use of ibuprofen (RR, 0.51; CI, 0.28-0.96) was greater than for aspirin (RR, 0.79; CI, 0.60-1.03). Subgroup analysis by breast cancer risk factors did not result in effect modification. Regular use of acetaminophen (an analgesic agent with little or no anti-inflammatory activity) or low-dose aspirin (<100 mg) was unrelated to the incidence of breast cancer. Our results indicate that the regular use of aspirin, ibuprofen, or other NSAIDs may have a significant chemopreventive effect against the development of breast cancer and underscore the need for clinical trials to confirm this effect.     

A large cohort study of nonsteroidal anti-inflammatory drug use and melanoma incidence

Results of laboratory studies indicate that nonsteroidal anti-inflammatory drugs (NSAIDs) may have chemopreventive activity and therapeutic efficacy against melanoma. However, few published epidemiological studies have examined the association between NSAID use and melanoma risk. We examined whether NSAID use was associated with melanoma risk among 63 809 men and women in the Vitamins and Lifestyle (VITAL) cohort study. Participants self-reported NSAID use (low-dose aspirin, regular or extra-strength aspirin, and nonaspirin NSAIDs) during the previous 10 years and data related to their melanoma risk factors on a baseline questionnaire. After linkage of the VITAL database to the NCI Surveillance, Epidemiology, and End Results cancer registry, 349 patients with incident melanoma were identified through December 31, 2005. Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of melanoma by NSAID use as categorized by overall use, duration of use, and dose (expressed as average number of days of use during the past 10 years). All statistical tests were two-sided. After adjusting for melanoma risk factors and indications for NSAID use, no association between NSAID use and melanoma risk was found. When use of at least 4 d/wk was compared with nonuse, no melanoma risk reduction was detected for any NSAID dose (HR = 1.12, 95% CI = 0.84 to 1.48), for any NSAID excluding low-dose aspirin (HR = 1.03, 95% CI = 0.74 to 1.43), for regular- or extra-strength aspirin (HR = 1.10, 95% CI = 0.76 to 1.58), or for nonaspirin NSAIDs (HR = 1.22, 95% CI = 0.75 to 1.99). Moreover, NSAID use was not associated with tumor invasion (P(interaction) = .38), tumor thickness (P(trend) = .98), or risk of metastasis (HR = 1.09, 95% CI = 0.32 to 3.62). NSAIDs do not appear to be good candidates for the chemoprevention of melanoma.     

NSAID use and breast cancer risk in the VITAL cohort

OBJECTIVE: We prospectively evaluated the association between average 10-year use of NSAIDs and invasive breast cancer. METHODS: Between 2000-2002, 35,323 postmenopausal women participating in the Vitamins And Lifestyle (VITAL) study provided detailed information regarding NSAID use, lifestyle and breast cancer risk factors. Using a Cox proportional hazards model, we analyzed associations between NSAID use and incident breast cancer (N = 482) ascertained through linkage to the SEER cancer registry. RESULTS: Use of low-dose aspirin at 4+ days/week over ten years was associated with a decreased risk of breast cancer (HR 0.65, confidence interval [CI] 0.43-0.97) versus no use, as was moderate use of other types of NSAIDs (HR 0.78, CI 0.61-0.98) for 10-yr average use up to 3 days/week. However, more frequent use of NSAIDs other than low-dose aspirin was associated with an increased risk (HR 1.26, CI 0.96-1.65), particularly frequent use of regular or extra strength aspirin (HR 1.43, CI 1.02-2.00). CONCLUSIONS: We did not find evidence of a global protective effect of NSAID use for the development of breast cancer. However, long-term moderate use (frequent use of low doses or moderate frequency of high doses) was associated with reduced risk, while frequent use of higher dose products was associated with increased risk.     

Nonsteroidal anti-inflammatory drugs and glioma in the NIH-AARP Diet and Health Study cohort

Several case-control studies have suggested that nonsteroidal anti-inflammatory drugs (NSAIDs) reduce risk for glioblastoma, an aggressive form of brain cancer. Prospective investigations have not observed such an association, but these studies lacked adequate brain cancer case numbers and did not stratify by histologic subtype. We prospectively investigated the association between NSAID use and risk of all glioma as well as the risk of glioblastoma subtype in the National Institutes of Health (NIH)-AARP Diet and Health Study. The frequency of aspirin and nonaspirin NSAID use 1 year prior to baseline was ascertained using a self-administered questionnaire. Hazard ratios (HRs) and 95% confidence intervals (CI) were estimated using Cox regression models with age as the underlying time metric, adjusted for sex, race, and history of heart disease. The analysis included 302,767 individuals, with 341 incident glioma cases (264 glioblastoma). No association was observed between regular use (>2 times/wk) of aspirin and risk of glioma (HR = 1.16; 95% CI, 0.87-1.56) or glioblastoma (HR = 1.17; 95% CI, 0.83-1.64) as compared with no use. Null associations were also observed for nonaspirin NSAID use (HR for glioma = 0.90; 95% CI, 0.65-1.25 and HR for glioblastoma = 0.83; 95% CI, 0.56-1.20) as compared with no use. Our findings from this large prospective study do not support an inverse association between NSAIDs and risk of all glioma or glioblastoma.     

Use of analgesics and nonsteroidal anti-inflammatory drugs, genetic predisposition, and bladder cancer risk in Spain.

BACKGROUND: We assessed use of nonaspirin nonsteroidal anti-inflammatory drugs (NSAID), aspirin, paracetamol (acetaminophen), phenacetin, and metamizol (dipyrone) and risk of bladder cancer and their interaction with polymorphisms in drug-metabolizing genes. METHODS: We analyzed personal interview data from 958 incident bladder cancer cases and 1,029 hospital controls from a multicenter case-control study in Spain. A drug matrix was developed to estimate cumulative lifetime dose of active ingredients. Polymorphisms in GSTP1, SULT1A1, CYP2E1, CYP2C9, and NAT2 were examined. RESULTS: A significant reduction in bladder cancer risk [adjusted odds ratio (OR), 0.4; 95% confidence interval (95% CI), 0.2-0.9] was observed for regular users of nonaspirin NSAIDs compared with never users. Regular users of aspirin experienced no reduction in risk (OR, 1.0; 95% CI, 0.7-1.5). Regular users of paracetamol had no overall increased risk of bladder cancer (OR, 0.8; 95% CI, 0.4-1.3), but our data suggested a qualitative interaction with the GSTP1 I105V genotype. Subjects with at least one copy of the 359L or 144C variant alleles in the NSAID-metabolizing gene CYP2C9 had a slightly decreased risk of bladder cancer (OR, 0.8; 95% CI, 0.7-1.0; P = 0.037); however, having at least one copy of the 359L or 144C variant alleles did not significantly modify the protective effect of nonaspirin NSAID use. CONCLUSION: Regular use of nonaspirin NSAIDs was associated with a reduced risk of bladder cancer, which was not modified by polymorphisms in the NSAID-metabolizing gene CYP2C9. We found no evidence of an overall effect for paracetamol or aspirin use.     

Association between nonsteroidal anti-inflammatory drug use and the incidence of lung cancer in the Iowa women's health study.

BACKGROUND: Previous studies have suggested that use of aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) may be associated with reduced risk of lung cancer, but the data are inconsistent and are limited particularly with respect to the effects of aspirin, separate from other NSAIDs. METHODS: The Iowa Women's Health Study is a prospective cohort of 41,836 Iowa women ages 55 to 69 years old at baseline in 1986. NSAID use was assessed in 1992. Over 10 years of follow-up, 403 incident cases of lung cancer were identified. The association of incident lung cancer with current use of aspirin or non-aspirin NSAIDs was analyzed after adjustment for lung cancer risk factors. Hazard ratios (HR) were estimated using multivariate COX proportional hazards regression. RESULTS: There were 27,162 women in the analytic cohort. After controlling for age, education, alcohol intake, pack-years, smoking status, body mass index, and total fruit intake, the RR of women taking six or more aspirin weekly was 1.21 (95% confidence interval, 0.92-1.59). The HR was 1.23 for women taking six or more non-aspirin NSAIDs weekly (95% confidence interval, 0.92-1.65). There was no statistically significant trend by frequency of use for either aspirin (P(trend) = 0.22) or non-aspirin NSAIDs (P(trend) = 0.53). Analyses by histologic type and smoking status yielded similar null results. Information on dosage and duration of use were not available for this analysis. CONCLUSION: These findings do not suggest that aspirin or other NSAIDs reduce risk of lung cancer in this cohort of postmenopausal women.     

Nonsteroidal antiinflammatory drug use and risk of bladder cancer in the health professionals follow-up study

Nonsteroidal antiinflammatory drugs (NSAIDs) use, particularly aspirin, may lower the risk of several cancers, including bladder. NSAIDs may reduce development of bladder tumors by decreasing inflammation, inhibiting cycloxygenase-2, inhibiting proliferation and inducing apoptosis of cancer cells. However, acetaminophen, a major metabolite of phenacetin, may be positively associated with bladder cancer risk. Results from case-control studies on NSAIDs and acetaminophen use and bladder cancer risk are inconsistent. We investigated the association between NSAID and acetaminophen use and bladder cancer risk in a large cohort of US males. Among 49,448 men in the Health Professionals Follow-Up Study, 607 bladder cancer cases were confirmed during 18 years of follow-up. Relative risks (RR) and 95% confidence intervals (CI) were calculated by Cox proportional hazards models. Multivariate RR were adjusted for age, current smoking status, pack years, geographic region and fluid intake. No significant associations were observed for regular aspirin (> or =2 tablets per week), (RR = 0.99, 95% CI 0.83-1.18), ibuprofen (RR = 1.11, 95% CI 0.81-1.54), acetaminophen (RR = 0.96, 95% CI 0.67-1.39) or total NSAID use (not including acetaminophen; RR = 1.01, 95% CI 0.85-1.20) and bladder cancer risk compared with nonuse. Consistent use (over 6 years) of aspirin, ibuprofen, acetaminophen and total NSAIDs, compared to nonuse, was not associated with bladder cancer risk. No association was observed between aspirin frequency and dose and bladder cancer risk. We observed no effect-modification by smoking, age or fluid intake. Our results suggest that regular NSAID or acetaminophen use has no substantial impact on bladder cancer risk among men.     

A large cohort study of nonsteroidal anti-inflammatory drugs and renal cell carcinoma incidence in the National Institutes of Health–AARP Diet and Health Study

Aim

Existing epidemiologic evidence for the association between nonsteroidal anti-inflammatory drugs (NSAIDs) and renal cell carcinoma (RCC) risk is inconsistent.

Methods

We investigated the association between the use of aspirin and nonaspirin NSAIDs and RCC risk in the National Institutes of Health–American Association of Retired Persons (AARP) Diet and Health Study, for which 298,468 AARP members free of cancer, aged 50–71 years, completed a survey on use of NSAIDs (1996–1997). Multivariate Cox proportional hazards models were used to estimate the hazard ratio (HR).

Results

The state cancer registry and mortality index linkage identified 1,084 incident RCC cases through 31 December 2006. No statistically significant associations between the use of aspirin or nonaspirin NSAIDs and RCC risk were found. Compared to nonuse of any NSAIDs, the multivariate-adjusted HRs were 0.95 (95 % CI 0.75–1.21) and 0.93 (95 % CI 0.68–1.26) for monthly use of aspirin and nonaspirin NSAIDs, respectively, 0.92 (95 % CI: 0.69-1.23) and 1.11 (95 % CI: 0.76-1.62) for weekly use, 0.87 (95 % CI: 0.69-1.11) and 1.06 (95 % CI: 0.75-1.48) for daily use; and 0.95 (95 % CI 0.78–1.14) for the use of both aspirin and nonaspirin NSAIDs. We found some suggestions of an increased risk of RCC associated with frequent NSAID use among participants who were <63 years and a reduced risk associated with aspirin use among those ≥63 years. No significant associations were found in other stratified analyses by gender, BMI, smoking, history of diabetes, or history of hypertension.

Conclusion

RCC risk was not significantly associated with NSAID use overall. The difference in association by age needs to be explored further.     

Medication use and risk of ovarian carcinoma: a prospective study

Inflammation and gonadotropins are hypothesized to influence ovarian carcinogenesis. In a prospective study, we evaluated ovarian cancer risk associated with self-reported use of medications that influence inflammation or gonadotropin levels. The Breast Cancer Detection Demonstration Project Follow-Up Study enrolled 61,431 women in 1979 and used telephone interviews and 3 mailed questionnaires through 1998 to update risk factor information and identify incident ovarian cancers. The 1992-95 questionnaire ascertained medication use, including duration and frequency of use for aspirin, acetaminophen, other nonsteroidal anti-inflammatory drugs (NSAIDs), tranquilizers and histamine-receptor antagonists. A Poisson regression analysis generated rate ratios (RRs) and 95% confidence intervals (CIs) for the 31,364 women who were at risk of ovarian cancer and responded to the questionnaire that queried regular medication use. One hundred sixteen women developed ovarian cancer during follow-up. None of the anti-inflammatory medications was associated with ovarian cancer, but the RR for more than 1 aspirin per day for 1 year or longer was 0.56 (95% CI 0.20-1.5) and the RR for more than 5 years of regular "other NSAID" use was 2.0 (95% CI 0.95-4.2). Regular tranquilizer use was not associated with ovarian cancer, but histamine-receptor antagonists used regularly for more than 5 years (RR = 3.6, 95% CI 1.4-9.1) or more than once daily (RR = 3.1, 95% CI 1.5-6.5) appeared to increase risk. In our study, neither anti-inflammatory medications nor anti-psychotic medications were associated with ovarian cancer. Potential associations with histamine-receptor antagonists may warrant further study.     

Mouse mammary tumor like virus sequences in breast milk from healthy lactating women

Aspirin and other non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) can inhibit aromatase activity and thus could selectively lower incidence of hormone receptor positive tumors. We assessed whether the association of aspirin and other NSAIDs with postmenopausal breast cancer risk differs by estrogen and progesterone receptor (ER and PR) status of the tumor. A population-based cohort of 26,580 postmenopausal women was linked to a SEER Cancer Registry to identify incident breast cancers. Regular use of aspirin and other NSAIDs was reported on a self-administered questionnaire mailed in 1992. Cox proportional hazards models were used to estimate multivariate relative risks (RRs) and 95% confidence intervals (CIs) of breast cancer incidence overall and by ER and PR status, adjusting for multiple breast cancer risk factors. Through 2005, 1,581 incident breast cancer cases were observed. Compared to aspirin never users, women who regularly consumed aspirin had a lower risk of breast cancer (RR = 0.80; 95% CI: 0.71–0.90), and there was evidence for lower risk with increasing frequency of use (RR = 0.71 for aspirin use 6 or more times/week vs. never use; P trend = 0.00001). Inverse associations for regular aspirin use were observed for ER+ (RR = 0.77; 95% CI 0.67–0.89), ER− (RR = 0.78; 95% CI 0.56–1.08), PR+ (RR = 0.79; 95% CI 0.68–0.92), and PR− (RR = 0.73; 95% CI 0.56–0.95) breast cancers. In contrast, use of other NSAIDs was not associated with breast cancer incidence overall (RR = 0.95, 95% CI: 0.85–1.07), or by ER or PR status. Aspirin, but not other NSAID use, was associated with about 20% lower risk of postmenopausal breast cancer and did not vary by ER or PR status of the tumor, suggesting that the hypothesized protective effects of aspirin may either be through cellular pathways independent of estrogen or progesterone signaling, or on tumor microenvironment.     

Association between nonsteroidal anti-inflammatory drug use and the incidence of pancreatic cancer

Laboratory studies indicate that nonsteroidal anti-inflammatory drugs (NSAIDs) may inhibit pancreatic cancer, but epidemiologic data to support this finding are limited. We conducted a prospective study from 1992 through 1999 among 28 283 postmenopausal women who lived in Iowa to examine the association between the self-reported use of aspirin and other NSAIDs and the incidence of pancreatic cancer. Eighty incident cases of pancreatic cancer were identified during 7 years of follow-up. The multivariate-adjusted relative risk of pancreatic cancer associated with any current use of aspirin versus no use was 0.57 (95% confidence interval = 0.36 to 0.90). There was a trend of decreasing risk of pancreatic cancer incidence with increasing frequency of aspirin use per week (P(trend) =.005). Nonaspirin NSAID use was not associated with incident pancreatic cancer. These data indicate that aspirin might be chemopreventive for pancreatic cancer.     

Association of aspirin and other non-steroidal anti-inflammatory drug use with incidence of non-Hodgkin lymphoma

Non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, seem to have chemopreventive properties against several types of cancer, particularly colon cancer. Persons with rheumatoid arthritis, an autoimmune disease for which NSAIDs are used commonly, have been reported to be at lower risk of colon cancer but at elevated risk of non-Hodgkin lymphoma (NHL), raising the possibility that NSAIDs may be a risk factor for NHL. We evaluated the association of use of NSAIDs, arthritis history, and risk of NHL in a prospective cohort of 27,290 postmenopausal women from the state of Iowa. The frequency of use of aspirin and of other NSAIDs excluding aspirin (e.g., ibuprofen), as well as a physician diagnosis of rheumatoid arthritis (RA) or osteoarthritis (OA), were self-reported on a questionnaire mailed in 1992. The incidence of NHL was ascertained through annual linkages to the Iowa SEER Cancer Registry. Relative risks (RR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards regression. Through 7 years of follow-up, 131 cases of NHL were identified. Compared to women who did not use either aspirin or other non-aspirin NSAIDs, women using aspirin exclusively (RR = 1.71; 95% CI = 0.94-3.13), non-aspirin NSAIDs exclusively (RR = 2.39; 95% CI = 1.18-4.83), or both types of drugs (RR = 1.97; 95% CI = 1.06-3.68) were at increased risk of NHL. A diagnosis of RA (RR = 1.75; 95% CI = 1.09-2.79), but not OA (RR = 1.06; 95% CI = 0.67-1.68), was associated with risk of NHL, but the positive association of use of aspirin and other NSAIDs with NHL was independent of RA history. Multivariate adjustment for other NHL risk factors only attenuated slightly these associations, whereas exclusion of cases occurring during the first 2 years of follow-up strengthened the associations. These data suggest that use of NSAIDs, either aspirin or other non-aspirin NSAIDs, are associated positively with risk of NHL, and that this association is independent of RA history.     

NSAID use and survival after breast cancer diagnosis in post-menopausal women

Many epidemiologic studies, although not all, have shown an inverse relation between non-steroidal anti-inflammatory drug (NSAID) use and risk of incident breast cancer, but the possible influence of NSAID use on breast cancer survival has not been evaluated. We examined the association between self-reported NSAID use and survival after invasive breast cancer diagnosis among 591 postmenopausal women in a prospective study. Cox proportional hazards regression was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for breast cancer death as well as all-cause mortality associated with NSAID use. There was an indication of reduced risk of breast cancer mortality and all-cause mortality for women reporting any versus no use of NSAIDs, with multivariate-adjusted HRs of 0.64 (95% CI 0.39–1.05) and 0.57 (95% CI 0.40–0.81), respectively. There was no trend of decreasing risk of death with increasing frequency of NSAID use per week. While the results from this exploratory analysis are preliminary, there is biological plausibility for such an association. Further studies should consider whether NSAIDs, which have biological activity affecting tumor promotion and progression and appear to protect against breast cancer incidence, may be associated with better prognosis after a diagnosis of invasive breast cancer. This study was supported by NIH grant National Cancer Institute RO1CA39742     

NSAIDs and breast cancer recurrence in a prospective cohort study

Objective We examined the association between NSAID use and breast cancer recurrence in a prospective cohort of 2,292 early-stage breast cancer survivors diagnosed from 1997 to 2000 participating in the Life After Cancer Epidemiology (LACE) Study. Methods From 2000 to 2002, mailed questionnaires were used to obtain information on aspirin, ibuprofen, and other NSAID use and subsequent breast cancer events. A total of 270 recurrences (local, regional, and distant disease and new primary breast cancers) were reported and verified by medical record review. Cox proportional hazard models were used to estimate rate ratios (RR) and 95% confidence intervals (CI), adjusting for age at diagnosis, race, cancer stage, tamoxifen treatment, chemotherapy use, body mass index, and cyclooxygenase-2 (COX2) inhibitor use. Results Current, regular use (at least three days per week at time of questionnaire administration) of ibuprofen (RR, 0.56; 95% CI, 0.32–0.98), but not aspirin (RR, 1.09; 95% CI, 0.74–1.61), was associated with a statistically significant decreased risk of breast cancer recurrence. The combination of ibuprofen and other non-aspirin NSAIDs such as naproxen and sulindac reflected a similar reduction in risk (RR, 0.56; 95% CI, 0.33–0.95). No association was found for the non-NSAID analgesic acetaminophen. Conclusion Our findings provide support for an inverse association between current, regular ibuprofen use and breast cancer recurrence.     

Non-steroidal anti-inflammatory drugs (NSAIDs) and breast cancer risk: differences by molecular subtype

Use of non-steroidal anti-inflammatory drugs (NSAIDs) has been associated with reduced risk of breast cancer, though findings have been inconsistent. This inconsistency may result from differences in etiology for breast tumors of different subtypes. We examined the association between NSAID use and breast cancer characterized by molecular subtypes in a population-based case-control study in Western New York. Cases (n = 1,170) were women with incident, primary, histologically confirmed breast cancer. Controls (n = 2,115) were randomly selected from NY Department of Motor Vehicles records (<65 years) or Medicare rolls (≥ 65 years). Participants answered questions regarding their use of aspirin and ibuprofen in the year prior to interview and their use of aspirin throughout their adult life. Logistic regression models estimated odds ratios (OR) and 95% confidence intervals (95% CI). Recent and lifetime aspirin use was associated with reduced risk, with no differences by subtype. Recent use of ibuprofen was significantly associated with increased risk of ER+/PR+(OR 1.33, 95% CI: 1.09-1.62), HER2- (OR 1.27, 95% CI: 1.05-1.53), and p53- breast cancers (OR 1.28, 95% CI: 1.04-1.57), as well as luminal A or B breast cancers. These findings support the hypothesis of heterogeneous etiologies of breast cancer subtypes and that aspirin and ibuprofen vary in their effects.