title: Use of non-steroidal anti-inflammatory drugs and risk of breast cancer: The Spanish Multi-Case-control (MCC) study.
abstract: 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).
  
  
  
  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.
  
  
  
  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.
  
  
  
  Most NSAIDs, but not aspirin, showed an inverse association against breast cancer; this effect seems to be restricted to hormone + or HER2+ cancers.
authors.affiliation: CIBER Epidemiologia y Salud Publica (CIBERESP), Madrid, Spain. dierssent@unican.es.|University of Cantabria - IDIVAL, Santander, Spain. dierssent@unican.es.
authors.forename: Trinidad
authors.initials: T
authors.lastname: Dierssen-Sotos
authors.affiliation: CIBER Epidemiologia y Salud Publica (CIBERESP), Madrid, Spain.|University of Cantabria - IDIVAL, Santander, Spain.
authors.forename: Inés
authors.initials: I
authors.lastname: Gómez-Acebo
authors.affiliation: Department of Obstetrics and Gynecology, Nuevo Belén University Hospital, Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: de Pedro
authors.affiliation: CIBER Epidemiologia y Salud Publica (CIBERESP), Madrid, Spain.|Cancer and Environmental Epidemiology Unit, National Center for Epidemiology, Carlos III Institute of Health, Madrid, Spain.|Cancer Epidemiology Research Group, Oncology and Hematology Area, IIS Puerta de Hierro (IDIPHIM), Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Pérez-Gómez
authors.affiliation: Servei d'Oncologia Mèdica, Hospital del Mar, Barcelona, Spain.|Cancer Research Program IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: Servitja
authors.affiliation: CIBER Epidemiologia y Salud Publica (CIBERESP), Madrid, Spain.|Cancer Prevention and Control Program, Catalan Institute of Oncology-IDIBELL, and University of Barcelona, Barcelona, Spain.
authors.forename: Víctor
authors.initials: V
authors.lastname: Moreno
authors.affiliation: CIBER Epidemiologia y Salud Publica (CIBERESP), Madrid, Spain.|Public Health Division of Gipuzkoa, Biodonostia Research Institute, San Sebastian, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Amiano
authors.affiliation: Área de Medicina Preventiva y Salud Pública, Departamento de Ciencias Biomédicas, Universidad de León, León, España.|Grupo de Investigación en Interacciones Gen-Ambiente y Salud (GIIGAS), Universidad de León, León, España.
authors.forename: Tania
authors.initials: T
authors.lastname: Fernandez-Villa
authors.affiliation: Navarra Public Health Institute, Pamplona, Spain.|Navarra Institute for Health Research (IdiSNA), Pamplona, Spain.
authors.forename: Aurelio
authors.initials: A
authors.lastname: Barricarte
authors.affiliation: CIBER Epidemiologia y Salud Publica (CIBERESP), Madrid, Spain.|IUOPA, Universidad de Oviedo, Oviedo, Spain.
authors.forename: Adonina
authors.initials: A
authors.lastname: Tardon
authors.affiliation: Universidad de Huelva, Huelva, Spain.|Centro de Investigación en Salud y Medio Ambiente (CYSMA), Huelva, Spain.
authors.forename: Marian
authors.initials: M
authors.lastname: Diaz-Santos
authors.affiliation: CIBER Epidemiologia y Salud Publica (CIBERESP), Madrid, Spain.|Area de Cáncer y Salud Pública, Fundación FISABIO- Salud Pública, Valencia, Spain.
authors.forename: Rosana
authors.initials: R
authors.lastname: Peiro-Perez
authors.affiliation: Epidemiology Unit and Girona Cancer Registry, Oncology Coordination Plan, Department of Health, Autonomous Government of Catalonia and Descriptive Epidemiology, Genetics and Cancer Prevention Group [Girona Biomedical Research Institute (IdIBGi)], Catalan Institute of Oncology, Girona, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Marcos-Gragera
authors.affiliation: CIBER Epidemiologia y Salud Publica (CIBERESP), Madrid, Spain.|Cancer and Environmental Epidemiology Unit, National Center for Epidemiology, Carlos III Institute of Health, Madrid, Spain.|Cancer Epidemiology Research Group, Oncology and Hematology Area, IIS Puerta de Hierro (IDIPHIM), Madrid, Spain.
authors.forename: Virginia
authors.initials: V
authors.lastname: Lope
authors.affiliation: CIBER Epidemiologia y Salud Publica (CIBERESP), Madrid, Spain.|Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.|Universitat Pompeu Fabra (UPF), Barcelona, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Gracia-Lavedan
authors.affiliation: CIBER Epidemiologia y Salud Publica (CIBERESP), Madrid, Spain.|Cancer Prevention and Control Program, Catalan Institute of Oncology-IDIBELL, and University of Barcelona, Barcelona, Spain.
authors.forename: M Henar
authors.initials: MH
authors.lastname: Alonso
authors.affiliation: Onkologikoa- Oncology Institute Gipuzkoa, San Sebastian, Spain.
authors.forename: Maria Jesus
authors.initials: MJ
authors.lastname: Michelena-Echeveste
authors.affiliation: Sección de Oncología, Complejo Asistencial Universitario de León, León, Spain.
authors.forename: Andrés
authors.initials: A
authors.lastname: Garcia-Palomo
authors.affiliation: CIBER Epidemiologia y Salud Publica (CIBERESP), Madrid, Spain.|Navarra Public Health Institute, Pamplona, Spain.|Navarra Institute for Health Research (IdiSNA), Pamplona, Spain.
authors.forename: Marcela
authors.initials: M
authors.lastname: Guevara
authors.affiliation: CIBER Epidemiologia y Salud Publica (CIBERESP), Madrid, Spain.|Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.|Universitat Pompeu Fabra (UPF), Barcelona, Spain.|IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Castaño-Vinyals
authors.affiliation: CIBER Epidemiologia y Salud Publica (CIBERESP), Madrid, Spain.|Cancer and Environmental Epidemiology Unit, National Center for Epidemiology, Carlos III Institute of Health, Madrid, Spain.|Cancer Epidemiology Research Group, Oncology and Hematology Area, IIS Puerta de Hierro (IDIPHIM), Madrid, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Aragonés
authors.affiliation: CIBER Epidemiologia y Salud Publica (CIBERESP), Madrid, Spain.|Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.|Universitat Pompeu Fabra (UPF), Barcelona, Spain.
authors.forename: Manolis
authors.initials: M
authors.lastname: Kogevinas
authors.affiliation: CIBER Epidemiologia y Salud Publica (CIBERESP), Madrid, Spain.|Cancer and Environmental Epidemiology Unit, National Center for Epidemiology, Carlos III Institute of Health, Madrid, Spain.|Cancer Epidemiology Research Group, Oncology and Hematology Area, IIS Puerta de Hierro (IDIPHIM), Madrid, Spain.
authors.forename: Marina
authors.initials: M
authors.lastname: Pollán
authors.affiliation: CIBER Epidemiologia y Salud Publica (CIBERESP), Madrid, Spain.|University of Cantabria - IDIVAL, Santander, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Llorca
mesh_terms: D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000473:pathology* / Q000517:prevention & control; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008875:Middle Aged; D016017:Odds Ratio; D017698:Postmenopause; D017697:Premenopause; D012307:Risk Factors; D013030:Spain / Q000453:epidemiology; D011795:Surveys and Questionnaires
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal
keywords: Breast cancer; HER2 positive breast cancer; Hormone receptor positive breast cancer; Non-steroidal anti-inflammatory drug; Triple negative breast cancer