Is there an estimate of the rate of breast cancer overdiagnosis in contemporary mammography practice accounting for the detection of non-progressive cancer?

The American Cancer Society recommends the following:

Women between 40 and 44 have the option to start screening with a mammogram every year.
Women 45 to 54 should get mammograms every year.
Women 55 and older can switch to a mammogram every other year, or they can choose to continue yearly mammograms. Screening should continue as long as a woman is in good health and is expected to live at least 10 more years.

Women who are at high risk for breast cancer based on certain factors should get a breast MRI and a mammogram every year, starting at age 30. This includes women who:
Have a lifetime risk of breast cancer of about 20% to 25% or greater.
Have a known BRCA1 or BRCA2 gene mutation.
Have a first-degree relative with a BRCA1 or BRCA2 gene mutation, and have not had genetic testing themselves.
Had radiation therapy to the chest when they were between the ages of 10 and 30 years.
Have Li-Fraumeni syndrome, Cowden syndrome, or Bannayan-Riley-Ruvalcaba syndrome, or have a first-degree relatives with one of these syndromes. [1]

The U.S. Preventive Services Task Force (USPSTF) recommends the following:

Biennial mammography screening is recommended for women aged 50 to 74 years.
The decision to start screening mammography in women prior to age 50 years should be an individual one.
There is insufficient evidence to assess the balance of benefits and harms of screening mammography in women aged 75 years or older. [2]

The American College of Obstetricians and Gynecologists recommend the following:

Mammography screening should be offered starting at the age of 40, and recommended no later than 50, and should continue to the age of 75. The decision for annual vs biennial screening can be made after shared discussion with a counselor. [3]

Overdiagnosis estimates are associated with uncertainty due the heterogeneity elements of the disease and screening process. To better understand the extent of overdiagnosis, simulation models were used to estimate outcomes. The model indicated per 1,000 women screened versus no screening:
biennial screening from age 50 to 74 years, 7 breast cancer deaths are averted and 19 cases are over-diagnosed
biennial screening from age 40 to 74 years, 8 breast cancer deaths are averted and 21 cases are over-diagnosed [4]

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

Design

Cohort study using Bayesian inference to estimate overdiagnosis

N= 35,986

Objective

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

Inclusion Criteria

Women aged 50 to 74 years whose first screen occurred at a Breast Cancer Surveillance Consortium (BCSC) facility between 2000 and 2018 from four BCSC registries.

Exclusion Criteria

Had received a mammogram or a breast cancer diagnosis before their first mammogram in the BCSC registry.

Methods

This study took place at a variety of BCSC facilities. As per the researchers, the BCSC is a racially, ethnically, and geographically diverse cohort that is representative of the mammography screening population in the United States.

Data on screen and interval cancer incidence was used to estimate the underlying latency and fraction of indolent cancer. These estimates, along with life tables on the risk for death from causes other than breast cancer, were used to predict the extent of overdiagnosis in a cohort of women undergoing regular mammography screening.

The rate of breast cancer overdiagnosis was defined as the proportion of screen-detected cancer cases that were either nonprogressive or progressive but would not have progressed to clinical disease before the woman died of causes unrelated to breast cancer.

To estimate this proportion, a cohort of women whose parameters for disease natural history were given by the best-fitting parameter combinations and who had regular screening, starting at age 50 years and until age 74 years or death from a cause unrelated to breast cancer, whichever occurred first, were considered.

The competing mortality risk was modeled on a published age–cohort model for a 1971 birth cohort. Residual uncertainty around the predicted mean rate of overdiagnosis was captured by 95% prediction intervals (PIs).

Outcome Measures

Parameter estimates:

Preclinical onset rate for patients aged 40 to 55

Preclinical onset rate for patients aged 55 to 65

Preclinical onset rate for patients aged 65 and up

Mean sojourn time

Fraction indolent cancers

Screening episode sensitivity

Predicted overdiagnosis rates for a biennial screening program at:

Overall

At first screen (age 50 y)

At fifth screen (age 58 y)

At ninth screen (age 66 y)

At thirteenth screen (age 74 y)

Baseline characteristics

Screening participants, n	35,986
Median age at first screen (IQR) [range], y	56 (52-64) [50-74]
Race, n (%):
White	20,001 (55.6)
Asian	5,897 (16.4)
Black	3,754 (10.4)
Other	1,417 (3.9)
Unknown	4,917 (13.7)
Ethnicity, n (%):
Hispanic	3,704 (10.3)
Non-Hispanic	29,964 (83.3)
Unknown	2,318 (6.4)
Screens, n	82,677
Screens per participant, mean (range)	2.3 (1–17)
Screens per participant, median (IQR)	1 (1–3)
Number of screens, n (%) of participants:
1	18,451 (51.3)
2	7,114 (19.8)
3	3,848 (10.7)
4	2,211 (6.1)
5	1,516 (4.2)
>6	2,846 (7.9)
Cancer, n	718
Mode of cancer detection, n (%):
Screen detected	645 (90.0)
Interval	73 (10.0)
Cancer type, n (%):
Invasive	530 (73.8)
In situ	141 (19.6)
Unknown	47 (6.5)

Results

Parameter Estimates:

Preclinical onset rate for ages [40, 55], y-1	0.0017 (0.0015–0.0021)
Preclinical onset rate for ages [55, 65], y-1	0.0029 (0.0024–0.0033)
Preclinical onset rate for ages [65, Infinity],y-1	0.0035 (0.0029–0.0042)
Mean sojourn time, y	6.6 (4.9–8.6)
Fraction indolent cancers, %	4.5 (0.1–14.8)
Screening episode sensitivity, %	81.4 (73.1–88.7)

Predicted Overdiagnosis Rates:

Overdiagnosis Measure	Mean Predicted Overdiagnosis Rate (95% Prediction Interval), %
Overall:
Total	15.4 (9.4–26.5)
Indolent cancer contribution	6.1 (0.2–20.1)
Progressive cancer contribution	9.3 (5.5–13.5)
At first screen (age 50 y):
Total	11.5 (3.8–28.3)
Indolent cancer contribution	8.4 (0.3–26.4)
Progressive cancer contribution	3.1 (1.6–5.1)
At fifth screen (age 58 y):
Total	11.6 (6.5–21.1)
Indolent cancer contribution	5.4 (0.2–16.8)
Progressive cancer contribution	6.2 (3.7–9.5)
At ninth screen (age 66 y):
Total	16.7 (11.3–25.4)
Indolent cancer contribution	5.4 (0.2–16.8)
Progressive cancer contribution	11.3 (7.1–16.0)
At 13^th screen (age 74 y):
Total	23.6 (17.7–31.9)
Indolent cancer contribution	5.5 (0.2–17.0)
Progressive cancer contribution	18.1 (11.9–24.5)

Study Author Conclusions

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 over-diagnosed.

InpharmD^TM Researcher

Critique

The BCSC database is encounter based, and thus it was not possible to distinguish between women who were lost to follow up and those who had not yet come back for their next screening exam. Additionally, there was exclusion of women with first mammography screening outside BCSC, which could have lowered event numbers.

References:

Ryser MD, Lange J, Inoue LYT, O'Meara ES, Gard C, Miglioretti DL, Bulliard JL, Brouwer AF, Hwang ES, Etzioni RB. Estimation of Breast Cancer Overdiagnosis in a U.S. Breast Screening Cohort. Ann Intern Med. 2022 Mar 1. doi: 10.7326/M21-3577. Epub ahead of print. PMID: 35226520.