Study Suggests Overdiagnosis in More Than 15 Percent of Mammography-Detected Breast Cancer Cases

New research suggests that approximately one out of seven cases of screen-detected breast cancer is overdiagnosed in patients between 50 and 74 years of age.

Drawing from the Breast Cancer Surveillance Consortium (BCSC), researchers assessed nearly 36,000 women, reviewed 82,677 mammograms and 718 breast cancer diagnoses, according to the recently published study in Annals of Internal Medicine.¹ Looking at biennial screening in women ranging between 50 to 74 years of age, the study authors estimated that 15.4 percent of screen-detected cases of breast cancer were overdiagnosed. Out of these overdiagnosed cases, the researchers attributed 9.3 percent to progressive pre-clinical cancer in women who would have died from another unrelated cause prior to clinical diagnosis and 6.1 percent to indolent pre-clinical cancer.

“Such a decomposition of overdiagnosis into its principal sources is rarely reported, and it allows for a more informative characterization of age-dependent patterns of overdiagnosis,” wrote Marc D. Ryser, PhD, an assistant professor of population health sciences and mathematics at Duke University, and colleagues.

According to the study, the bilateral screening mammograms were performed at least nine months after the preceding mammogram. The researchers noted that cancer diagnoses included invasive breast cancer and preinvasive ductal carcinoma in situ (DCIS) lesions.

Ryser and colleagues predicted a mean overdiagnosis rate of 8.4 percent for indolent cancer for the first mammography screen at age 50 with this percentage dropping to 5.4 percent at the fifth mammography screen at age 58 and largely remaining at that percentage through a 13th screen at age 74. In contrast, they noted a 3.1 percent mean overdiagnosis rate for progressive cancer at the first screening at age 50. This percentage rate doubled to 6.2 percent by the fifth mammography screening at age 58 and nearly tripled to 18.1 percent by the 13th screen at age 74, according to the study.

The study authors also speculated that a large percentage of the overdiagnosed lesions in the study may have been DCIS lesions. Citing previous research showing that between 70 to 80 percent of DCIS lesions are non-progressive, and that 20 percent of screen-detected lesions are DCIS, Ryser and colleagues said these statistics suggest that DCIS diagnosis contributes to overdiagnosis in approximately 15 percent of screen-detected cancer cases.^2,3

“Because this estimate coincides with our overall overdiagnosis estimate, we hypothesize that overdiagnosis may be infrequent among cases of invasive cancer,” wrote Ryser and colleagues.

The study authors acknowledge that an inability to estimate natural histories for DCIS and invasive cancer due to identifiability issues in this study prohibited a formal assessment of this hypothesis. In regard to other study limitations, Ryser and colleagues conceded that data from the BCSC is encounter-based, which prohibited distinguishing between patients lost to follow-up and those who had not returned for a subsequent screening exam. With the study being limited to women who had their first screening within the BCSC, the study authors acknowledged that resulting event numbers were too low to address factors, such as breast density, race and ethnicity, as well as molecular or histologic subtypes.

In an accompanying editorial, Felippe O. Marcondes, MD and Katrina Armstrong, MD, who are affiliated with the Division of General Internal Medicine in the Department of Medicine at Massachusetts General Hospital in Boston, praised the research by Ryser and colleagues as an “important step forward” in addressing controversial uncertainty over the probability of overdiagnosis in breast cancer screening.⁴

In order to eliminate or reduce overdiagnosis, Marcondes and Armstrong said there needs to be greater clarity about the progression of breast tumors. They also called for continued efforts to enhance the accuracy of screening techniques.

References

1. Ryser MD, Lange J, Inoue LYT, et al. Estimation of breast cancer overdiagnosis in a U.S. breast screening cohort. Ann Intern Med. 2022 Mar 1. Doi: 10.7326/M21-3577. Online ahead of print.

2. Ryser MD, Weaver DL, Zhao F, et al. Cancer outcomes in DCIS patients without locoregional treatment. J Natl Cancer Inst. 2019;11(9):952-960.

3. Erbas B, Provenzano E, Armes J, et al. The natural history of ductal carcinoma in situ of the breast: a review. Breast Cancer Res Treat. 2006;97(2):135-44.

4. Marcondes FO, Armstrong K. Reducing the burden of overdiagnosis in breast cancer screening and beyond. Ann Intern Med. 2022 Mar 1. Doi: 10.7326/M22-0483. Online ahead of print.