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.
Design: Comparative modeling study.
Data Sources: Surveillance, Epidemiology, and End Results program, Breast Cancer Surveillance Consortium, and medical literature.
Target Population: A contemporary cohort of women eligible for routine screening.
Time Horizon: Lifetime.
Intervention: Mammography screening starting at age 40 versus 50 years with different screening methods (film, digital) and screening intervals (annual, biennial).
Outcome Measures: Benefits: 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 of Base-Case Analysis: 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 of Sensitivity Analysis: The threshold RRs changed slightly when a more comprehensive measure of harm was used and were relatively insensitive to lower adherence assumptions.
Limitation: Risk was assumed to influence onset of disease without influencing screening performance.
Conclusion: 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.
Primary Funding Source: National Cancer Institute.