title: Tipping the balance of benefits and harms to favor screening mammography starting at age 40 years: a comparative modeling study of risk.
abstract: BACKGROUND
  Timing of initiation of screening for breast cancer is controversial in the United States.
  
  
  OBJECTIVE
  To determine the threshold relative risk (RR) at which the harm-benefit ratio of screening women aged 40 to 49 years equals that of biennial screening for women aged 50 to 74 years.
  
  
  METHODS
  Comparative modeling study.
  
  
  METHODS
  Surveillance, Epidemiology, and End Results program, Breast Cancer Surveillance Consortium, and medical literature.
  
  
  METHODS
  A contemporary cohort of women eligible for routine screening.
  
  
  METHODS
  Lifetime.
  
  
  CONCLUSIONS
  Societal.
  
  
  METHODS
  Mammography screening starting at age 40 versus 50 years with different screening methods (film, digital) and screening intervals (annual, biennial).
  
  
  METHODS
  
  
  
  RESULTS
  life-years gained, breast cancer deaths averted; harms: false-positive mammography findings; harm-benefit ratios: false-positive findings/life-years gained, false-positive findings/deaths averted.
  
  
  RESULTS
  Screening average-risk women aged 50 to 74 years biennially yields the same false-positive findings/life-years gained as biennial screening with digital mammography starting at age 40 years for women with a 2-fold increased risk above average (median threshold RR, 1.9 [range across models, 1.5 to 4.4]). The threshold RRs are higher for annual screening with digital mammography (median, 4.3 [range, 3.3 to 10]) and when false-positive findings/deaths averted is used as an outcome measure instead of false-positive findings/life-years gained. The harm-benefit ratio for film mammography is more favorable than for digital mammography because film has a lower false-positive rate.
  
  
  RESULTS
  The threshold RRs changed slightly when a more comprehensive measure of harm was used and were relatively insensitive to lower adherence assumptions.
  
  
  CONCLUSIONS
  Risk was assumed to influence onset of disease without influencing screening performance.
  
  
  CONCLUSIONS
  Women aged 40 to 49 years with a 2-fold increased risk have similar harm-benefit ratios for biennial screening mammography as average-risk women aged 50 to 74 years. Threshold RRs required for favorable harm-benefit ratios vary by screening method, interval, and outcome measure.
  
  
  BACKGROUND
  National Cancer Institute.
authors.affiliation: Erasmus Medical Center, Rotterdam, the Netherlands. n.vanravesteyn@erasmusmc.nl
authors.forename: Nicolien T
authors.initials: NT
authors.lastname: van Ravesteyn
authors.forename: Diana L
authors.initials: DL
authors.lastname: Miglioretti
authors.forename: Natasha K
authors.initials: NK
authors.lastname: Stout
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Lee
authors.forename: Clyde B
authors.initials: CB
authors.lastname: Schechter
authors.forename: Diana S M
authors.initials: DS
authors.lastname: Buist
authors.forename: Hui
authors.initials: H
authors.lastname: Huang
authors.forename: Eveline A M
authors.initials: EA
authors.lastname: Heijnsdijk
authors.forename: Amy
authors.initials: A
authors.lastname: Trentham-Dietz
authors.forename: Oguzhan
authors.initials: O
authors.lastname: Alagoz
authors.forename: Aimee M
authors.initials: AM
authors.lastname: Near
authors.forename: Karla
authors.initials: K
authors.lastname: Kerlikowske
authors.forename: Heidi D
authors.initials: HD
authors.lastname: Nelson
authors.forename: Jeanne S
authors.initials: JS
authors.lastname: Mandelblatt
authors.forename: Harry J
authors.initials: HJ
authors.lastname: de Koning
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000453:epidemiology* / Q000401:mortality; D055088:Early Detection of Cancer; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D008327:Mammography; D008403:Mass Screening / Q000379:methods*; D008875:Middle Aged; D015233:Models, Statistical; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D013997:Time Factors; D014481:United States / Q000453:epidemiology