Study: Screening responsible for ‘widespread overdiagnosis’ of breast cancer

Just when you thought it was safe to sidestep arguably the most hotly debated clinical topic in healthcare, along comes a mammoth, population-based study to show that regular mammograms seem to be producing “widespread overdiagnosis” of breast cancer.

Published July 6 in JAMA Internal Medicine, the study looked at 16 million women at least 40 years old in 547 U.S. counties reporting to cancer registries. The key finding: the more mammograms performed in a given geographic area, the more small tumors and precancerous tumors turned up—but with no increase in findings of larger tumors and no drop in breast cancer-associated death rates.

Lead author Charles Harding, a Seattle-based data scientist, worked with co-authors from Harvard and Dartmouth to analyze county-level relationships between breast cancer diagnoses and screening mammography according to tumor size. They found a very strong association between screening and detection of tumors less than 2 cm in size at diagnosis. Indeed, the counties highest in screenings ferreted out some 2.2 times more of these tiny tumors than the counties with the fewest screenings. At the same time, the counties with the most screening had 1.8 times as many breast cancers diagnosed as counties with the least screening.

However, for tumors larger than 2 cm, there was very little screening-detection association—and no reduction in the rate of breast cancer diagnosis.

“I think this tells us that the potential for overdiagnosis is very high,” Harding told JAMA IM in an audio interview posted on the publication’s website. “Overdiagnosis was perhaps the clearest result of screening when analyzed at the population level.”

The study's ecological design will likely provide fuel for those inclined to challenge its conclusions. The design is generally used to test broad hypotheses. It wasn’t intended to find out, in this instance, whether the women who were screened were the same women who were diagnosed or in some way helped by their screenings.

The 16 million subjects reported to the Surveillance, Epidemiology, and End Results cancer registries during the year 2000. Of these women, 53,207 were diagnosed with breast cancer that year and followed up for the next 10 years. The study covered the period Jan. 1, 2000, to Dec. 31, 2010, and the analysis was performed between April 2013 and March 2015.

Joann Elmore, MD, MPH, of the University of Washington in Seattle, co-wrote an accompanying opinion piece for JAMA IM. In the audio interview, she said the hard part now is drawing from the new study to make decisions about breast cancer screening.

“We are increasingly realizing that there are harms associated with breast cancer screening, and the benefit is less than we had hoped for,” Elmore said. “We are not able, though, to give the exact percentage of cases that are over-detected. And, perhaps even more importantly, we’re not able to tell a new patient who has just been diagnosed with breast cancer if she is overdiagnosed or not. We probably need more help from basic scientists to guide this. In the meantime, we are having to try and talk with patients and help them make informed choices.”

Women deserve to hear information about benefits as well as potential harms, Elmore added, “but we will also have to share with them some of the uncertainties.”

“[O]bserved mortality from breast cancer may be too rare and too noisy to reliably detect the 20 percent reduction at 13 years of follow-up that was estimated in a comprehensive meta-analysis of screening mammography trials,” concluded Harding and colleagues in their study. They added that questions about both the failure to catch true cancers before they become large and the lack of association between screening and reduced mortality from breast cancer at the 10-year followup mark are “promising topics for future research. This is also the right time to begin investigating whether all women undergoing screening mammography have the same risk of overdiagnosis, or if overdiagnosis is especially likely in some groups.”

JAMA IM has posted the study and the associated commentary.