New Review Reveals Flaws of Influential Canadian RCTs on Mammography Screening

While the efficacy of mammography for breast cancer screening has been demonstrated in a majority of published randomized controlled trials (RCTs), two Canadian RCTs failed to find a benefit for the use of mammography for women ranging between 40 to 59 years of age.^1,2 However, newly published research in the Journal of Breast Imaging (JBI) reveals significant flaws in the methodology and execution of the Canadian studies.³

Published in 1992, the influential Canadian National Breast Screening Studies (CNBSS) assessed the efficacy of mammography in 50,430 women between the ages of 40 to 49 with a mean follow-up of 8.5 years, and another study population of women between the ages of 50 to 59 with a mean follow-up of 8.3 years.^1,2 The study authors noted no impact of annual mammography screening upon breast cancer mortality rates for women in either of the two studies with up to seven years of follow-up.

However, the authors of the new JBI research said there were a number of flaws with the CNBSS research including the study’s inclusion of women with breast cancer symptoms; violation of the randomization process required of RCTs; the use of poor quality mammography devices; and insufficient power to ascertain differences in mortality for people with breast cancer.³

Sarah M. Friedewald, MD, FACR, concurred with the authors of the JBI article.

“The most significant flaw in the trials was the lack of adherence to randomized controlled trial (RCT) protocols, including improper randomization of patients (purposefully moving patients with palpable abnormalities after a clinical breast examination into the mammography group) and recruitment of symptomatic patients into this screening trial that should have only included asymptomatic patients,” noted Dr. Friedewald, the vice chair of clinical operations and women’s imaging, and an associate professor in the Department of Radiology at the Feinberg School of Medicine at Northwestern University. “These violations resulted in diminishing the effectiveness of mammography and explain why there was a higher incidence of breast cancers in the mammography arm.”

Lead author Jean M. Seely, MD, who is affiliated with the Department of Medical Imaging at the University of Ottawa in Canada, and colleagues noted seemingly contradictory findings in the CNBSS studies as well as survival rates that ran counter to established breast cancer survival rates at that time.

The JBI authors pointed out that the first CNBSS study, looking at mammography in patients between the ages of 40 and 49, found a higher number of deaths from cancers detected in the first mammography screening in comparison to the usual care arm of the study.^1,3 Yet there was a “markedly lower” number of deaths from cancer detected by mammography alone in comparison to those detected via physical examination with or without mammography, according to Dr. Seely and colleagues.

In the second CNBSS study, examining mammography use for women aged 50 to 59, researchers noted similar seven-year survival rates between the study groups (90.2 percent for mammography vs. 89.9 percent in the non-mammography arm) that were 10 to 15 percent higher than reported five-year breast cancer survival rates at that time, according to the authors of the JBI review.^2,3

Dr. Friedewald noted that national organizations have relied upon the CNBSS trials “for decades” to shape mammography guidelines in the United States. She says the findings by Seely and colleagues as well as simultaneously published firsthand accounts of staff who participated in the administration of the CNBSS trials should change that moving forward.

“The CNBSS trials should not be used as evidence in forming guidelines as the results are not representative of the true benefits of mammography,” emphasized Dr. Friedewald, the medical director of the Lynn Sage Comprehensive Breast Center in Chicago. “ … By eliminating these trials from meta-analyses of RCTs on the effectiveness of screening mammography, it will be even more evident that the most lives are saved when women are screened annually beginning at age 40. This should result in long-term support for insurance coverage for annual mammography screening for women, including women in their 40s.”

In regard to future research, Dr. Friedewald would like to see more of a focus on investigating effective treatment for breast cancer “rather than repeating studies which already show that early detection with mammography reduces mortality.”

References

Miller AB, Baines CJ, To T, Wall C. Canadian National Breast Screening Study: 1. Breast cancer detection and death rates among women aged 40 to 49 years. CMAJ. 1992;147(10):1459-1476.

Miller AB, Baines CJ, To T, Wall C. Canadian National Breast Screening Study: 2. Breast cancer detection and death rates among women aged 50 to 59 years. CMAJ. 1992;147(10):1477-1488.

Seely JM, Eby PR, Yaffe MJ. The fundamental flaws of the CNBSS trials: a scientific review. Journal of Breast Imaging. 2022. https://doi.org/10.1093/jbi/wbab099. Published March 29, 2022. Accessed March 29, 2022.