title: Pooled analysis of active cigarette smoking and invasive breast cancer risk in 14 cohort studies.
abstract: The 2014 US Surgeon General's report noted research gaps necessary to determine a causal relationship between active cigarette smoking and invasive breast cancer risk, including the role of alcohol consumption, timing of exposure, modification by menopausal status and heterogeneity by oestrogen receptor (ER) status.
  
  
  
  To address these issues, we pooled data from 14 cohort studies contributing 934 681 participants (36 060 invasive breast cancer cases). Cox proportional hazard regression models were used to calculate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs).
  
  
  
  Smoking duration before first birth was positively associated with risk ( P -value for trend = 2 × 10 -7 ) with the highest HR for initiation >10 years before first birth (HR = 1.18, CI 1.12-1.24). Effect modification by current alcohol consumption was evident for the association with smoking duration before first birth ( P -value=2×10 -4 ); compared with never-smoking non-drinkers, initiation >10 years before first birth was associated with risk in every category of alcohol intake, including non-drinkers (HR = 1.15, CI 1.04-1.28) and those who consumed at least three drinks per day (1.85, 1.55-2.21). Associations with smoking before first birth were limited to risk of ER+ breast cancer ( P -value for homogeneity=3×10 -3 ). Other smoking timing and duration characteristics were associated with risk even after controlling for alcohol, but were not associated with risk in non-drinkers. Effect modification by menopause was not evident.
  
  
  
  Smoking, particularly if initiated before first birth, was modestly associated with ER+ breast cancer risk that was not confounded by amount of adult alcohol intake. Possible links with breast cancer provide additional motivation for young women to not initiate smoking.
authors.affiliation: Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA.
authors.forename: Mia M
authors.initials: MM
authors.lastname: Gaudet
authors.affiliation: Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Carter
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
authors.forename: Louise A
authors.initials: LA
authors.lastname: Brinton
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
authors.forename: Roni T
authors.initials: RT
authors.lastname: Falk
authors.affiliation: Department of Community Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway.
authors.forename: Inger T
authors.initials: IT
authors.lastname: Gram
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Indiana University, Bloomington, IN, USA.
authors.forename: Juhua
authors.initials: J
authors.lastname: Luo
authors.affiliation: Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, VIC, Australia and Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Victoria, Australia.
authors.forename: Roger L
authors.initials: RL
authors.lastname: Milne
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.|Department of Radiology, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Nyante
authors.affiliation: Department of Community Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway.|Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.|Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway.|Genetic Epidemiology Group, Folkhälsan Research Center, Helsinki, Finland.
authors.forename: Elisabete
authors.initials: E
authors.lastname: Weiderpass
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Beane Freeman
authors.affiliation: Epidemiology Branch, National Institute of Environmental Health Sciences, NIH/DHHS, Research Triangle Park, NC, USA.
authors.forename: Dale P
authors.initials: DP
authors.lastname: Sandler
authors.affiliation: Department of Epidemiology and Biostatistics, Milken Institute School of Public Health, George Washington University, Washington, DC, USA.
authors.forename: Kim
authors.initials: K
authors.lastname: Robien
authors.affiliation: School of Public Health, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Kristin E
authors.initials: KE
authors.lastname: Anderson
authors.affiliation: Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, VIC, Australia and Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Victoria, Australia.
authors.forename: Graham G
authors.initials: GG
authors.lastname: Giles
authors.affiliation: Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.|Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA, USA.
authors.forename: Wendy Y
authors.initials: WY
authors.lastname: Chen
authors.affiliation: Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Diane
authors.initials: D
authors.lastname: Feskanich
authors.affiliation: Department of Community Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø, Norway.
authors.forename: Tonje
authors.initials: T
authors.lastname: Braaten
authors.affiliation: Department of Oncology, School of Medicine, Georgetown University, Washington, DC, USA.|Lombardi Comprehensive Cancer Center at Georgetown University, Washington, DC, USA.
authors.forename: Claudine
authors.initials: C
authors.lastname: Isaacs
authors.affiliation: University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
authors.forename: Lesley M
authors.initials: LM
authors.lastname: Butler
authors.affiliation: Duke-NUS Graduate Medical School Singapore, Singapore, Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore.
authors.forename: Woon-Puay
authors.initials: WP
authors.lastname: Koh
authors.affiliation: Department of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
authors.forename: Alicja
authors.initials: A
authors.lastname: Wolk
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.|Department of Epidemiology, Harvard T.H. Chan School of Public Health Community, Boston, MA, USA.
authors.forename: Hans-Olov
authors.initials: HO
authors.lastname: Adami
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.|Department of Epidemiology, University of Washington, Seattle, Washington, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: White
authors.affiliation: HealthPartners Institute for Education and Research, Minneapolis, MN, USA.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Margolis
authors.affiliation: Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Thun
authors.affiliation: Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Gapstur
mesh_terms: D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000453:epidemiology*; D001943:Breast Neoplasms / Q000453:epidemiology*; D000073865:Cigarette Smoking / Q000009:adverse effects / Q000453:epidemiology*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D054547:National Cancer Institute (U.S.); D016016:Proportional Hazards Models; D011960:Receptors, Estrogen / Q000235:genetics; D012307:Risk Factors; D014481:United States
chemical_list: D011960:Receptors, Estrogen
keywords: alcohol; breast cancer; tobacco smoking