title: Initiators and promoters for the occurrence of screen-detected breast cancer and the progression to clinically-detected interval breast cancer.
abstract: BACKGROUND
  The risk factors responsible for breast cancer have been well documented, but the roles of risk factors as initiators, causing the occurrence of screen-detected breast cancer, or promoters, responsible for the progression of the screen-detected to the clinically-detected breast cancer, have been scarcely evaluated.
  
  
  METHODS
  We used data from women in a cohort in Kopparberg (Dalarna), Sweden between 1977 and 2010. Conventional risk factors, breast density, and tumor-specific biomarkers are superimposed to the temporal course of the natural history of the disease.
  
  
  RESULTS
  The results show that older age at first full-term pregnancy, dense breast, and a family history of breast cancer increased the risk of entering the preclinical screen-detectable phase of breast cancer by 23%, 41%, and 89%, respectively. Overweight/obesity (body mass index ≥25 kg/m2) was a significant initiator (adjusted relative risk [aRR] 1.15; 95% confidence interval [CI], 0.99-1.33), but was inversely associated with the role of promoter (aRR 0.65; 95% CI, 0.51-0.82). Dense breast (aRR 1.46; 95% CI, 1.12-1.91), triple-negative (aRR 2.07; 95% CI, 1.37-3.15), and Ki-67 positivity (aRR 1.66; 95% CI, 1.19-2.30) were statistically significant promoters. When the molecular biomarkers were considered collectively as one classification, the basal-like subtype was the most influential subtype on promoters (aRR 4.24; 95% CI, 2.56-7.02) compared with the Luminal A subtype.
  
  
  CONCLUSIONS
  We ascertained state-dependent covariates of initiators and promoters to classify the risk of the two-step progression of breast cancer. The results of the current study are useful for individually-tailored screening and personalized clinical surveillance of patients with breast cancer that was detected at an early stage.
authors.affiliation: School of Oral Hygiene, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Amy Ming-Fang
authors.initials: AM
authors.lastname: Yen
authors.affiliation: Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; Department of Radiation Sciences, Umeå University, Umeå, Sweden.
authors.forename: Wendy Yi-Ying
authors.initials: WY
authors.lastname: Wu
authors.affiliation: Department of Mammography, Falun Central Hospital, Falun, Sweden.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Tabar
authors.affiliation: Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK.
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Duffy
authors.affiliation: Cancer Control Science Department, American Cancer Society, Atlanta, GA, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Smith
authors.affiliation: Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan. Electronic address: chenlin@ntu.edu.tw.
authors.forename: Hsiu-Hsi
authors.initials: HH
authors.lastname: Chen
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D014408:Biomarkers, Tumor; D015992:Body Mass Index; D001940:Breast / Q000473:pathology; D000071060:Breast Density; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000000981:diagnostic imaging*; D018450:Disease Progression; D055088:Early Detection of Cancer / Q000379:methods; D006801:Humans; D042361:Mammary Glands, Human / Q000002:abnormalities*; D008327:Mammography / Q000379:methods*; D008875:Middle Aged; D057285:Precision Medicine; D011960:Receptors, Estrogen / Q000378:metabolism; D012307:Risk Factors; D013548:Sweden
chemical_list: D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen
keywords: Breast cancer; Multi-state; Personalized; Risk factor