Estimation of Breast Cancer Overdiagnosis in a U.S. Breast Screening Cohort

Abstract

Background: Mammography screening can lead to overdiagnosis-that is, screen-detected breast cancer that would not have caused symptoms or signs in the remaining lifetime. There is no consensus about the frequency of breast cancer overdiagnosis.

Objective: To estimate the rate of breast cancer overdiagnosis in contemporary mammography practice accounting for the detection of nonprogressive cancer.

Design: Bayesian inference of the natural history of breast cancer using individual screening and diagnosis records, allowing for nonprogressive preclinical cancer. Combination of fitted natural history model with life-table data to predict the rate of overdiagnosis among screen-detected cancer under biennial screening.

Setting: Breast Cancer Surveillance Consortium (BCSC) facilities.

Participants: Women aged 50 to 74 years at first mammography screen between 2000 and 2018.

Measurements: Screening mammograms and screen-detected or interval breast cancer.

Results: The cohort included 35 986 women, 82 677 mammograms, and 718 breast cancer diagnoses. Among all preclinical cancer cases, 4.5% (95% uncertainty interval [UI], 0.1% to 14.8%) were estimated to be nonprogressive. In a program of biennial screening from age 50 to 74 years, 15.4% (UI, 9.4% to 26.5%) of screen-detected cancer cases were estimated to be overdiagnosed, with 6.1% (UI, 0.2% to 20.1%) due to detecting indolent preclinical cancer and 9.3% (UI, 5.5% to 13.5%) due to detecting progressive preclinical cancer in women who would have died of an unrelated cause before clinical diagnosis.

Limitations: Exclusion of women with first mammography screen outside BCSC.

Conclusion: On the basis of an authoritative U.S. population data set, the analysis projected that among biennially screened women aged 50 to 74 years, about 1 in 7 cases of screen-detected cancer is overdiagnosed. This information clarifies the risk for breast cancer overdiagnosis in contemporary screening practice and should facilitate shared and informed decision making about mammography screening.

Primary funding source: National Cancer Institute.

Figure 1.

Overdiagnosis definition, data structure, and mathematical model. A. In the absence of screening, healthy women can develop preclinical cancer (t₁). After a period of asymptomatic but screen-detectable tumor latency (sojourn time), women with preclinical cancer develop clinical cancer (t₂). B. A screen-detected cancer at age t₃ is overdiagnosed if, in the absence of screening, death from a breast cancer unrelated cause (age t₄) would have occurred before onset with symptoms or signs (t₄ < t₃). C. On the other hand, the detected cancer is not overdiagnosed if the time of death would have occurred after onset with symptoms or signs (t₄ > t3). D. The screening and cancer diagnosis histories of women in the Breast Cancer Surveillance Consortium cohort can be assigned to 1 of 3 groups: no cancer diagnosis, diagnosis with a screen-detected cancer (gray square), and diagnosis with an interval cancer (red square). E. The mathematical model used for natural history estimation and overdiagnosis prediction has several components: (i) age-dependent incidence of preclinical cancer, (ii) fraction of preclinical cancer that is nonprogressive, (iii) sensitivity of screening tests, and (iv) tumor latency among progressive cancer.

Figure 2.

Data summary. In the middle and right panels, Gaussian kernel density estimates were used to smooth the data (see Supplement 1). Left. Participant age at first screen in the analyzed cohort. Middle. Time between consecutive screens, across all participants. Right. Cases of cancers (per 10 000 women) diagnosed during the first 5 screening rounds, across all participants and by method of detection.

Figure 3.

Overdiagnosis in women undergoing biennial screening, ages 50 to 74 years. For women undergoing biennial screening starting at age 50 years, the mean predicted overdiagnosis rate is shown by the height of each bar for each screen until age 74 years (gray lines represent the 95% prediction intervals). There are 2 sources of overdiagnosis: the detection of progressive preclinical cancer that would not have progressed to clinical cancer before death from a breast cancer unrelated cause (white) and the detection of nonprogressive preclinical cancer (green).