Skip Navigation


American Journal of Epidemiology Advance Access originally published online on August 14, 2007
American Journal of Epidemiology 2007 166(10):1150-1158; doi:10.1093/aje/kwm195
This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
166/10/1150    most recent
kwm195v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (7)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Gill, J. K.
Right arrow Articles by Kolonel, L. N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gill, J. K.
Right arrow Articles by Kolonel, L. N.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

American Journal of Epidemiology © The Author 2007. Published by the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

ORIGINAL CONTRIBUTIONS

Nonsteroidal Antiinflammatory Drugs and Breast Cancer Risk

The Multiethnic Cohort

Jasmeet K. Gill1, Gertraud Maskarinec1, Lynne R. Wilkens1, Malcolm C. Pike2, Brian E. Henderson2 and Laurence N. Kolonel1

1 Cancer Research Center of Hawaii, University of Hawaii, Honolulu, HI
2 Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA

Correspondence to Dr. Jasmeet K. Gill, Cancer Research Center of Hawaii, 1236 Lauhala Street, Honolulu, HI 96813 (e-mail: jgill{at}crch.hawaii.edu).

Received for publication March 19, 2007. Accepted for publication May 31, 2007.


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 
Previous studies on nonsteroidal antiinflammatory drugs (NSAIDs) and breast cancer have produced mixed results. Incident invasive cases of breast cancer from the Multiethnic Cohort (African Americans, Caucasians, Japanese Americans, Latinas, and Native Hawaiians from Hawaii and California) were identified from 1993 to 2002. Data on aspirin, acetaminophen, and other NSAID (ibuprofen, naproxen, indomethacin) use were based on a self-administered questionnaire at baseline (1993–1996). Multivariate Cox proportional hazards models provided estimates of hazard rate ratios and 95% confidence intervals. The authors observed no associations between breast cancer risk and duration of aspirin use for current or past users (hazard rate ratio = 1.05, 95% confidence interval: 0.88, 1.25 and hazard rate ratio = 1.04, 95% confidence interval: 0.84, 1.27 for ≥6 years of use, respectively) compared with nonusers. However, duration of current other NSAID use was protective (hazard rate ratio = 0.70, 95% confidence interval: 0.51, 0.95 for ≥6 years of use; ptrend = 0.01) against the risk of breast cancer, while past use was not (hazard rate ratio = 0.90, 95% confidence interval: 0.62, 1.30 for ≥6 years of use). Analyses by ethnicity and hormone receptor status showed that the protective effect of current other NSAID use was limited to Caucasians and African Americans and to women with at least one positive hormone receptor. This study found duration of current other NSAID use to be protective against breast cancer risk.

anti-inflammatory agents, non-steroidal; breast neoplasms; ethnic groups; risk

Abbreviations: CI, confidence interval; COX, cyclooxygenase; NSAID, nonsteroidal antiinflammatory drug


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 
Studies of breast tumors from humans and animals have suggested that cyclooxygenase (COX)-2 expression is associated with breast cancer development (1). COX-2 is an enzyme involved in the biosynthesis of prostaglandins. Increased COX-2 levels are associated with increased angiogenesis and estrogen synthesis and with reduced apoptosis (2). COX-2 up-regulation leads to overexpression of prostaglandin E2, which is thought to promote local estrogen biosynthesis via aromatase activity (1) and therefore increase risk of breast carcinogenesis. Nonsteroidal antiinflammatory drugs (NSAIDs) may reverse the expression of prostaglandin E2 (3), thereby reducing the local production of estrogens. A 2001 meta-analysis of any NSAID use and risk of breast cancer reported an odds ratio of 0.80 (95 percent confidence interval (CI): 0.73, 0.87) (4), and a recent pooled analysis of aspirin use and breast cancer reported a risk ratio of 0.90 (95 percent CI: 0.87, 0.94) (5). However, two recent, large cohort studies observed no protective effect of NSAID or aspirin use (6, 7). This analysis examines the association of duration of aspirin, other NSAIDs, and total NSAID use with breast cancer risk among female members of the Multiethnic Cohort (8).


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 References
 
Study population
Details of the Multiethnic Cohort have been described previously (8). In brief, data were collected between 1993 and 1996 by using a 26-page, self-administered, mail questionnaire sent to residents of Hawaii and California, mainly Los Angeles County. The institutional review boards at both locations approved the study. Subjects were identified through drivers' license records in both locations; in addition, voter registration records were used in Hawaii and Health Care Financing Administration files in California. African Americans, Caucasians, Japanese Americans, Latinas, and Native Hawaiians were the primary targets for recruitment, but a small number of persons of other ethnicities were also enrolled in the study. Participation in the cohort was limited to people aged 45–75 years in 1993, except for Native Hawaiians, who were recruited at age 42 years or older. The Multiethnic Cohort data set consists of 215,251 people, of whom 118,869 are women. The following women were excluded from this analysis: 1) 8,051 who do not belong to one of the five major ethnic groups; 2) 4,611 whose dietary records were invalid; 3) 6,654 who had a prior history of breast, uterine, or ovarian cancer based on questionnaire or cancer registry data because their cancer treatment may affect their risk of breast cancer; and 4) 633 diagnosed with in situ breast cancer during follow-up. Therefore, data on 98,920 women were available for this analysis.

Data collection
The questionnaire included demographic information, body weight and height, medication history, and dietary history (8). The following question was asked to assess pain medication use: "Have you ever taken any of the following medications at least two times per week (for 1 month or longer)?" The question was posed once for each of three categories of pain medication—aspirin, other NSAIDs (ibuprofen, naproxen, indomethacin, or other), and acetaminophen—and examples of brand names were provided. Cohort participants responded by circling "no," "yes, but not at this time," or "yes, currently." If participants answered "yes," they were asked to mark the length of medication use as 1 year or less, 2–3 years, 4–5 years, 6–10 years, or 11 years or more.

Case identification and follow-up
Follow-up time started at the date of entry into the cohort, defined as questionnaire completion or the date of the 45th birthday for the few Multiethnic Cohort members younger than age 45 years at baseline. Follow-up ended at the earliest of the following dates: 1) breast cancer diagnosis, 2) ovarian or uterine cancer diagnosis, 3) death, or 4) last date of follow-up. Breast cancer was the event of interest. Incident cases of cancer were identified through linkages with the Los Angeles County Cancer Surveillance Program, the State of California Cancer Registry, and the Hawaii Tumor Registry, all members of the Surveillance, Epidemiology, and End Results Program supported by the National Cancer Institute. Information on deaths was obtained from the vital statistics offices in both states and the National Death Index. Case ascertainment was complete through December 31, 2002. All invasive breast cancer cases were identified for the analysis.

Statistical analysis
We created four categories for use of aspirin, acetaminophen, and other NSAIDs: no use, up to 1 year, 2–5 years, and 6 years or more. We also created a total NSAID use variable (no use, up to 1 year, 2–5 years, 6–10 years, and 11 years or more), which combined years of use for aspirin and other NSAIDs, but not acetaminophen. The total NSAID variable summed total years of aspirin use and total years of other NSAID use; if duration information on one variable was missing, then total years of NSAID use was also assigned as missing. We had individuals who reported using pain medications but did not indicate the number of years of use, which we then treated as missing (3.0 percent for aspirin, 4.6 percent for other NSAIDs, and 5.0 percent for acetaminophen; table 1). Therefore, the total amount of missing information on pain medication use was 7.9 percent for aspirin, 10.8 percent for other NSAIDs, and 11.2 percent for acetaminophen.


View this table:
[in this window]
[in a new window]

  		TABLE 1. Distribution of study participants by ethnicity and pain medication use, the Multiethnic Cohort Study, 1993–2002

 
We applied multivariate Cox proportional hazards regression models with age as the time metric to estimate hazard rate ratios and 95 percent confidence intervals while adjusting for covariates (9). The analysis was stratified by follow-up period (≤2 years, >2–5 years, ≥5 years) in an attempt to account for any change in associations over time. The Cox proportional hazards assumption was tested by examining Kaplan-Meier survival curves and by assessing Schoenfeld residuals. All analyses were completed by using SAS version 9.1 software (10). All reported p values are two sided.

We used two models throughout the analyses: one model with the aspirin-, other NSAID-, and acetaminophen-use variables and a second model with total NSAID- and acetaminophen-use variables. All pain medications were considered in the models to adjust for pain-medication-taking behavior. Women who had never used any of the pain medications were the reference group for all models. We analyzed the association of each pain medication (aspirin, acetaminophen, other NSAIDs, and total NSAIDs) with breast cancer in two ways. First, the hazard rate ratio for each pain medication was estimated by adjusting for age at cohort entry and ethnicity (African American, Caucasian, Japanese American, Latina, and Native Hawaiian) only. Next, we added the baseline values for family history of breast cancer (none, mother/sister/daughter diagnosed with breast cancer), mammography screening history (never, more than 2 years ago, within 2 years), education (up to 12 years, more than 12 years), body mass index (<25, 25–<30, ≥30 kg/m2), alcohol intake (≤1 drink per day, >1–<2 drinks per day, ≥2 drinks per day), age at menarche (≤12, 13–14, ≥15 years), age at first full-term pregnancy (nulliparous, ≤20, 21–<31, ≥31 years), number of children for parous women (1, 2–3, ≥4), age at and type of menopause (natural: age <45, 45–<50, 50–<55, ≥55 years; oophorectomy: age <45, 45–<50, ≥50 years; hysterectomy: age <45, 45–<50, ≥50 years), and use of hormone replacement therapy (none, estrogen only, estrogen/progestin). Variables for trend tests were created by using the median value for each duration of use category (≤1 year, 2–5 years, etc.) for each pain medication. Tests for interaction were performed by using the Wald test, jointly comparing all interaction terms of duration of pain medication use and an indicator variable for current/past use against null values of zero (11). After we excluded women for whom values for model covariates were missing, 78,797 women remained.

We also performed separate analyses by ethnicity, body mass index (<25 and ≥25 kg/m2), use of hormone replacement therapy (no use, any use), and estrogen and progesterone receptor status (at least one positive receptor (estrogen and/or progesterone), no positive receptors).


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 References
 
For each of the three pain medications, nearly 60 percent of all study subjects stated that they had never used the medication (table 1). Current use of aspirin, other NSAIDs, and acetaminophen was 17.8 percent, 15.0 percent, and 16.6 percent, respectively. Japanese-American women included the highest proportion of nonusers for all categories of medication (aspirin, 75.7 percent; other NSAIDs, 78.7 percent; and acetaminophen, 72.3 percent) and the lowest proportion of current users (aspirin, 12.4 percent; other NSAIDs, 7.4 percent; and acetaminophen, 11.5 percent). African-American and Latina women included the highest percentage of current or past users of acetaminophen and other pain relief medications, and African-American and Caucasian women included the highest percentage of current or past users of aspirin. Native Hawaiians were similar to Japanese-American women regarding their patterns of aspirin and other NSAIDs use. However, their use of acetaminophen (current and past) was higher than that of Japanese-American and Caucasian women.

We observed no association between breast cancer and duration of current or past aspirin use (ptrend = 0.79 and ptrend = 0.80, respectively) in the fully adjusted models (table 2). The risk estimates for women using aspirin varied little by current or past use (for ≥6 years of use, hazard rate ratio = 1.05, 95 percent CI: 0.88, 1.25 and hazard rate ratio = 1.04, 95 percent CI: 0.84, 1.27, respectively). However, for women using other NSAIDs, the risk estimates differed by current and past use. We observed an association between duration of current use of other NSAIDs and breast cancer (ptrend = 0.01), but not for duration of past use (ptrend = 0.25). Current other NSAID use for 6 or more years decreased the risk of breast cancer by 30 percent (95 percent CI: 0.51, 0.95). A test of interaction between duration and an indicator variable of current/past use of other NSAIDs suggested a possible interaction (pinteraction = 0.07), signifying that total duration of current and past use should not be combined.


View this table:
[in this window]
[in a new window]

  		TABLE 2. Risk estimates for the association of current and past use of pain medications with breast cancer, the Multiethnic Cohort Study, 1993–2002*

 
Total NSAID use—current or past—was not associated with breast cancer (≥11 years of use: hazard rate ratio = 0.99, 95 percent CI: 0.82, 1.18 for current use and hazard rate ratio = 1.01, 95 percent CI: 0.82, 1.25 for past use). Acetaminophen, in accordance with its lack of COX-2 inhibitory properties, was not associated with breast cancer risk (≥6 years of use: hazard rate ratio = 0.87, 95 percent CI: 0.71, 1.06 for current use and hazard rate ratio = 1.05, 95 percent CI: 0.83, 1.33 for past use). We also examined the association of each pain medication with in situ breast cancer and found no associations (results not shown).

We observed the protective association of current duration of other NSAID use with breast cancer for African-American and Caucasian women only (table 3, ptrend = 0.02 for both ethnic groups). African-American women's risk decreased by 60 percent if they were current users of other NSAIDs for 6 or more years (95 percent CI: 0.17, 0.91), whereas Caucasian women had a 40 percent decrease in risk (95 percent CI: 0.36, 1.02). However, past other NSAID use did not decrease risk of breast cancer for any of the ethnic groups, although there was a suggestion of a trend with duration for Caucasian women (ptrend = 0.08). For Japanese, Latina, and Native-Hawaiian women, we found no association with current or past other NSAID use. Aspirin use was not associated with breast cancer for any of the ethnic groups, nor was total NSAID use.


View this table:
[in this window]
[in a new window]

  		TABLE 3. Risk estimates for the association of current and past use* of pain medications with breast cancer by ethnicity,{dagger} the Multiethnic Cohort Study, 1993–2002{ddagger}

 
Information on estrogen receptor and progesterone receptor status of tumors was available through our registries for 80 percent of all cases. Cases for whom information on estrogen receptor and progesterone receptor status was or was not available did not differ in their distribution of current/past aspirin or other NSAID use. Analyses by subgroups of women with breast cancer who had at least one positive estrogen receptor and/or progesterone receptor compared with women with both receptors negative showed differences in the strength of association by duration of current (ptrend = 0.02) versus past (ptrend = 0.15) other NSAID use (table 4). However, a test for interaction was not statistically significant (pinteraction = 0.77). Duration of current/past aspirin use or total NSAID use was not associated with risk of hormone receptor positive tumors or hormone receptor negative tumors.


View this table:
[in this window]
[in a new window]

  		TABLE 4. Risk estimates for the association of different pain medications with breast cancer risk by estrogen/progesterone receptor status,* the Multiethnic Cohort Study, 1993–2002{dagger},{ddagger}

 
Stratification by weight status as measured by body mass index did not indicate any differences in breast cancer risk estimates between overweight (≥25 kg/m2) and normal-weight (<25 kg/m2) women (results not shown). Use of hormone replacement therapy also did not change the association between current or past pain medication use and risk of breast cancer (results not shown).


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
References
 
We observed no association between aspirin use or total NSAID use and breast cancer risk among the female members of the Multiethnic Cohort study, but we did observe a protective effect of other NSAID use among current users. Longer duration of current other NSAID use was associated with a greater protective effect against breast cancer (ptrend = 0.01), and use for 6 or more years decreased risk by 30 percent. Past use of other NSAIDs was not associated with risk of breast cancer, suggesting a possible interaction between timing (current/past) of other NSAID use and duration (pinteraction = 0.07). After we performed analyses by ethnicity and by subgroups of hormone receptor status, the protective effect for the longest duration of current other NSAID use was limited to Caucasian and African-American women and to women with at least one positive hormone receptor.

Our findings agree with results from some cohort studies of NSAID use and breast cancer (12, 13) but not with others (6, 7, 14). The Women's Health Initiative and a Canadian cohort study of NSAIDs and aspirin found aspirin and other NSAIDs to be protective against breast cancer (12, 13). On the other hand, the Iowa Women's Health study (14) observed that daily aspirin use, but not use of the other NSAIDs, was protective against breast cancer, and the California Teacher's study and the American Cancer Society Cohort found neither aspirin nor ibuprofen to have a protective effect (6, 7). The California Teacher's study actually observed a higher risk of breast cancer with daily, regular ibuprofen use (risk ratio = 1.24, 95 percent CI: 1.07, 1.44). The lack of an association between aspirin use and breast cancer in our study may be a result of women taking primarily low-dose aspirin for heart disease prevention. As shown by a randomized trial and an observational study, low-dose aspirin does not appear to lower invasive breast cancer risk (13, 15).

Data from our study suggested a heterogeneity of effect by timing for other NSAID use, but two other studies that analyzed timing of NSAID use (7, 16) did not find differences such as ours. However, they did not analyze duration of current use and duration of past use separately. One study looked at current use versus past use for less than 5 years and past use for 5 or more years (16), while the other study compared past or less-than-regular use with current, regular use for less than 5 years and use for 5 or more years (7). The differences we observed across ethnic groups, especially among current users of other NSAIDs, could be due to biology, such as COX-2 polymorphisms, or they could reflect differences in patterns of and reasons for medication use. They could also be the result of residual confounding or unmeasured confounding. More research is required to clarify the role of timing of NSAID use on breast carcinogenesis as well as potential differences in risk across ethnic groups.

Similar to our study, a few others have found different patterns of risk by estrogen or progesterone receptor status (6, 16), but the findings have been inconsistent. Although our study found a protective association between breast cancer with at least one positive hormone receptor and duration of current other NSAID use but not duration of current aspirin use, the Long Island Breast Cancer Study Project found current and former aspirin use to have similar protective risk estimates for breast cancer cases with at least one positive hormone receptor (odds ratio = 0.74, 95 percent CI: 0.57, 0.96 and odds ratio = 0.79, 95 percent CI: 0.55, 1.13, respectively) (16). The California Teacher's Cohort found 5 or more years of daily aspirin use to suggest protection against breast cancer among women with estrogen- or progesterone-positive tumors (risk ratio = 0.80, 95 percent CI: 0.62, 1.03), while a similar duration and frequency of ibuprofen use increased risk of breast cancer (risk ratio = 1.50, 95 percent CI: 1.11, 2.03) (6). Further adding to the inconsistencies, the American Cancer Society Cohort and a 2005 case-control study found no difference in the association between NSAID use and breast cancer risk by hormone receptor status (7, 17). Thus, more research is needed before any conclusions can be made about the role of NSAIDs in the incidence of hormone-receptor-positive tumors.

Our study found no differences in risk for overweight (≥25 kg/m2) compared with normal-weight (<25 kg/m2) women. Results from three previous studies support our findings. A population-based case-control study and the American Cancer Society Cohort found no difference with aspirin and/or NSAID use across strata of body mass index (7, 18), and, whereas the Women's Health Initiative study found a 29 percent reduction in risk for women with a body mass index of ≥27 kg/m2 who used any NSAID for 5 or more years, a test for heterogeneity of effect was not statistically significant (12). Similarly, our study supports results from previous research showing that use of hormone replacement therapy does not change the relation between aspirin and/or NSAID use and breast cancer (7, 12, 16).

Menopausal status may modify the association between NSAIDs and breast cancer. A statistically significant reduction in risk was described for premenopausal but not postmenopausal women in one case-control study of NSAIDs (17), but another case-control study of aspirin use found just the opposite (16). The Nurses' Health Study observed a lower relative risk for aspirin users under age 50 years than for older women (0.79 and 1.06, respectively) (19). Since the Multiethnic Cohort is mostly composed of postmenopausal women, we were unable to address this question.

In contrast to relatively inconsistent results of cohort studies, the majority of case-control studies that examined aspirin or NSAID use reported them to be protective against breast cancer (4, 17, 18, 20–24). A recent pooled analysis of aspirin use and breast cancer produced risk ratios of 0.94 (95 percent CI: 0.90, 0.98) for 12 cohort studies and 0.80 (95 percent CI: 0.73, 0.87) for six case-control studies (5).

The inconsistencies across studies may be due to differences in exposure classification, study design, definition of use, age at data collection and start of medication, prevalence of medication use, and choice of covariates. Case-control studies appear to be more likely to report protective effects of NSAIDs (aspirin and/or ibuprofen). Recall bias and selection bias may be partly responsible for this repeated observation. The variations in results may also be due to unmeasured confounders, such as frequency of contact with health care providers and higher screening rates for women who obtain regular prescriptions. Compared with that for populations in other locations, the Multiethnic Cohort screening rate is relatively high; 89.7 percent of Caucasians, 87.9 percent of African Americans, 84.5 percent of Native Hawaiians, 88.9 percent of Japanese, and 81.4 percent of Latinas reported having had a previous mammogram.

Strengths of our study are the prospective design and the large number of breast cancer cases from different ethnic groups. In addition, recall bias should be minimal because medication use was ascertained before breast cancer diagnosis. A serious limitation of this study is a lack of detailed data on the frequency of medication use, dosage, and age at initiation that may have resulted in misclassification of exposure. We could not assess whether women were concurrently using the various pain medications or whether the patterns of use were unchanged until the time of diagnosis. Therefore, we assumed that aspirin and other NSAID use was nonconcurrent when analyzing by total NSAID use and that women's reported patterns of use at baseline did not change. We did not have data on the reasons for pain medication use and thus could not assess the role of comorbidities in duration of use. Our study had limited power for analyses of current or past pain medication use across the different ethnic groups and for analysis of estrogen-receptor-/progesterone-receptor-negative tumors. Furthermore, when the cohort was established, newer NSAIDs, such as selective COX-2 inhibitors, had not entered the market yet. Therefore, we were not able to study their effects.

In summary, this investigation suggests that the relation between other NSAID use and breast cancer may vary by timing of use, although we observed no associations for aspirin or total NSAID use, regardless of timing. Long-term current use of other NSAIDs appeared to be protective against breast cancer for Caucasians and African Americans and for women with at least one positive hormone receptor. There is much debate about the possible role of COX-2 inhibitors in breast cancer chemoprevention. However, the literature is inconsistent, and the benefits of such a regimen must be weighed against the potential side effects. It would be valuable for future research on NSAIDs to include a detailed assessment of medication use including frequency, duration, dose, type, and timing in addition to information on the frequency of contact with the health care system and comorbidities. Further analyses also need to be conducted across ethnic groups to verify our results that duration of current other NSAID use is protective for only Caucasian and African-American women.


   ACKNOWLEDGMENTS
 
The Multiethnic Cohort Study has been supported by US Public Health Service (National Cancer Institute) grant R37 CA 54281 (Principal Investigator: L. N. K.). One of the authors (J. G.) was supported by a postdoctoral fellowship on grant R25 CA 90956.

Conflict of interest: none declared.


   References
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 

  1. Arun B, Goss P. The role of COX-2 inhibition in breast cancer treatment and prevention. Semin Oncol (2004) 31(2 suppl 7):22–9.[Web of Science][Medline]
  2. Taketo MM. Cyclooxygenase-2 inhibitors in tumorigenesis (part I). J Natl Cancer Inst (1998) 90:1529–36.[Abstract/Free Full Text]
  3. Thun MJ, Henley SJ, Patrono C. Nonsteroidal anti-inflammatory drugs as anticancer agents: mechanistic, pharmacologic, and clinical issues. J Natl Cancer Inst (2002) 94:252–66.[Abstract/Free Full Text]
  4. Khuder SA, Mutgi AB. Breast cancer and NSAID use: a meta-analysis. Br J Cancer (2001) 84:1188–92.[CrossRef][Web of Science][Medline]
  5. Bosetti C, Gallus S, La Vecchia C. Aspirin and cancer risk: an updated quantitative review to 2005. Cancer Causes Control (2006) 17:871–88.[CrossRef][Web of Science][Medline]
  6. Marshall SF, Bernstein L, Anton-Culver H, et al. Nonsteroidal anti-inflammatory drug use and breast cancer risk by stage and hormone receptor status. J Natl Cancer Inst (2005) 97:805–12.[Abstract/Free Full Text]
  7. Jacobs EJ, Thun MJ, Connell CJ, et al. Aspirin and other nonsteroidal anti-inflammatory drugs and breast cancer incidence in a large U.S. cohort. Cancer Epidemiol Biomarkers Prev (2005) 14:261–4.[Abstract/Free Full Text]
  8. Kolonel LN, Henderson BE, Hankin JH, et al. A multiethnic cohort in Hawaii and Los Angeles: baseline characteristics. Am J Epidemiol (2000) 151:346–57.[Abstract/Free Full Text]
  9. Agresti A. Categorical data analysis. (2002) Hoboken, NJ: John Wiley & Sons.
  10. SAS Institute, Inc. SAS. OnlineDoc 9.1.2. (2004) Cary, NC: SAS Institute, Inc.
  11. Therneau T, Grambsch P. Modeling survival data: extending the Cox model. (2000) New York, NY: Springer-Verlag.
  12. Harris RE, Chlebowski RT, Jackson RD, et al. Breast cancer and nonsteroidal anti-inflammatory drugs: prospective results from the Women's Health Initiative. Cancer Res (2003) 63:6096–101.[Abstract/Free Full Text]
  13. Rahme E, Ghosn J, Dasgupta K, et al. Association between frequent use of nonsteroidal anti-inflammatory drugs and breast cancer. BMC Cancer (2005) 5:159.[CrossRef][Medline]
  14. Johnson TW, Anderson KE, Lazovich D, et al. Association of aspirin and nonsteroidal anti-inflammatory drug use with breast cancer. Cancer Epidemiol Biomarkers Prev (2002) 11:1586–91.[Abstract/Free Full Text]
  15. Cook NR, Lee IM, Gaziano JM, et al. Low-dose aspirin in the primary prevention of cancer: the Women's Health Study: a randomized controlled trial. JAMA (2005) 294:47–55.[Abstract/Free Full Text]
  16. Terry MB, Gammon MD, Zhang FF, et al. Association of frequency and duration of aspirin use and hormone receptor status with breast cancer risk. JAMA (2004) 291:2433–40.[Abstract/Free Full Text]
  17. Zhang Y, Coogan PF, Palmer JR, et al. Use of nonsteroidal antiinflammatory drugs and risk of breast cancer: the Case-Control Surveillance Study revisited. Am J Epidemiol (2005) 162:165–70.[Abstract/Free Full Text]
  18. Moorman PG, Grubber JM, Millikan RC, et al. Association between non-steroidal anti-inflammatory drugs (NSAIDs) and invasive breast cancer and carcinoma in situ of the breast. Cancer Causes Control (2003) 14:915–22.[CrossRef][Web of Science][Medline]
  19. Egan KM, Stampfer MJ, Giovannucci E, et al. Prospective study of regular aspirin use and the risk of breast cancer. J Natl Cancer Inst (1996) 88:988–93.[Abstract/Free Full Text]
  20. Coogan PF, Rao SR, Rosenberg L, et al. The relationship of nonsteroidal anti-inflammatory drug use to the risk of breast cancer. Prev Med (1999) 29:72–6.[CrossRef][Web of Science][Medline]
  21. Harris RE, Namboodiri K, Stellman SD, et al. Breast cancer and NSAID use: heterogeneity of effect in a case-control study. Prev Med (1995) 24:119–20.[CrossRef][Web of Science][Medline]
  22. Swede H, Mirand AL, Menezes RJ, et al. Association of regular aspirin use and breast cancer risk. Oncology (2005) 68:40–7.[CrossRef][Web of Science][Medline]
  23. Harris RE, Beebe-Donk J, Alshafie GA. Reduction in the risk of human breast cancer by selective cyclooxygenase-2 (COX-2) inhibitors. BMC Cancer (2006) 6:27.[CrossRef][Medline]
  24. Sharpe CR, Collet JP, McNutt M, et al. Nested case-control study of the effects of non-steroidal anti-inflammatory drugs on breast cancer risk and stage. Br J Cancer (2000) 83:112–20.[CrossRef][Web of Science][Medline]

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 JNCI J Natl Cancer InstHome page
B. Takkouche, C. Regueira-Mendez, and M. Etminan
Breast Cancer and Use of Nonsteroidal Anti-inflammatory Drugs: A Meta-analysis
J Natl Cancer Inst, October 15, 2008; 100(20): 1439 - 1447.
[Abstract] [Full Text] [PDF]

Home page
 JNCI J Natl Cancer InstHome page
L. R. Howe and S. M. Lippman
Modulation of Breast Cancer Risk by Nonsteroidal Anti-inflammatory Drugs
J Natl Cancer Inst, October 15, 2008; 100(20): 1420 - 1423.
[Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
166/10/1150    most recent
kwm195v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (7)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Gill, J. K.
Right arrow Articles by Kolonel, L. N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gill, J. K.
Right arrow Articles by Kolonel, L. N.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?