title: Nonsteroidal anti-inflammatory drug use and breast cancer risk by stage and hormone receptor status.
abstract: BACKGROUND
  Epidemiologic studies of the association between nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin and ibuprofen, and breast cancer risk have yielded inconsistent results. We investigated the association of NSAID use with risk of breast cancer in the California Teachers Study cohort, with special attention to risk of specific breast cancer subtypes and to type of NSAID used.
  
  
  METHODS
  We analyzed data on 114 460 women in the California Teachers Study cohort who were aged 22 to 85 years and free of breast cancer at baseline in 1995 to 1996. Information on frequency and duration of NSAID use was collected through a self-administered questionnaire. A total of 2391 women were diagnosed with breast cancer during the follow-up period from 1995 to 2001. We used Cox proportional hazards regression to estimate relative risks (RR) and 95% confidence intervals (CI) of breast cancer subtypes with NSAID use.
  
  
  RESULTS
  Neither regular use (more than once a week) of any NSAID (aspirin and ibuprofen combined) nor regular use of aspirin was associated with breast cancer risk (RR = 1.09, 95% CI = 0.97 to 1.21 for daily versus no regular use of NSAIDs and RR = 0.98, 95% CI = 0.86 to 1.13 for daily versus no regular use of aspirin). However, long-term (> or = 5 years) daily aspirin users had a non-statistically significant decreased risk of estrogen receptor and progesterone receptor (ER/PR)-positive breast cancer (RR = 0.80, 95% CI = 0.62 to 1.03). In contrast, we observed a statistically significantly increased risk of ER/PR-negative breast cancer with long-term daily use of aspirin (RR = 1.81, 95% CI = 1.12 to 2.92). In this population, 11 fewer ER/PR-positive breast cancer cases and seven excess ER/PR-negative breast cancer cases may be due to daily long-term aspirin use among 2391 breast cancer cases observed over 6 years if the association were proven to be causal. Long-term daily use of ibuprofen was also associated with an increased risk of breast cancer (RR = 1.51, 95% CI = 1.17 to 1.95), particularly of nonlocalized tumors (RR = 1.92, 95% CI = 1.24 to 2.97). If causality were subsequently proven, 16 of the observed 2391 breast cancer cases and 8 of the 713 non-localized breast cancer cases would be attributable to long-term daily use of ibuprofen.
  
  
  CONCLUSIONS
  Long-term daily use of NSAIDs was not associated with breast cancer risk overall. Ibuprofen use was associated with an increased risk of breast cancer, and long-term daily aspirin use was associated with an increased risk of ER/PR-negative breast cancer. However, it is not clear if the observed association is causal.
authors.affiliation: Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA. smarshal@usc.edu
authors.forename: Sarah F
authors.initials: SF
authors.lastname: Marshall
authors.forename: Leslie
authors.initials: L
authors.lastname: Bernstein
authors.forename: Hoda
authors.initials: H
authors.lastname: Anton-Culver
authors.forename: Dennis
authors.initials: D
authors.lastname: Deapen
authors.forename: Pamela L
authors.initials: PL
authors.lastname: Horn-Ross
authors.forename: Harvey
authors.initials: H
authors.lastname: Mohrenweiser
authors.forename: David
authors.initials: D
authors.lastname: Peel
authors.forename: Rich
authors.initials: R
authors.lastname: Pinder
authors.forename: David M
authors.initials: DM
authors.lastname: Purdie
authors.forename: Peggy
authors.initials: P
authors.lastname: Reynolds
authors.forename: Dan
authors.initials: D
authors.lastname: Stram
authors.forename: Dee
authors.initials: D
authors.lastname: West
authors.forename: William E
authors.initials: WE
authors.lastname: Wright
authors.forename: Argyrios
authors.initials: A
authors.lastname: Ziogas
authors.forename: Ronald K
authors.initials: RK
authors.lastname: Ross
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage* / Q000009:adverse effects; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects; D001241:Aspirin / Q000008:administration & dosage; D001943:Breast Neoplasms / Q000139:chemically induced / Q000737:chemistry / Q000453:epidemiology* / Q000473:pathology*; D002140:California / Q000453:epidemiology; D005178:Faculty / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage; D015994:Incidence; D016013:Likelihood Functions; D008875:Middle Aged; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011960:Receptors, Estrogen / Q000032:analysis*; D011980:Receptors, Progesterone / Q000032:analysis*; D012042:Registries; D012107:Research Design; D018570:Risk Assessment; D012307:Risk Factors; D011795:Surveys and Questionnaires
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D000082:Acetaminophen; D001241:Aspirin; D007052:Ibuprofen