“If women are to truly participate in the decision of whether or not to be screened [for breast cancer using mammography], they need some quantification of its benefits and harms,” asserted H. Gilbert Welch, MD, MPH, Professor of Medicine, and Honor J. Passow, PhD, Instructor, at The Dartmouth Institute for Health Policy & Clinical Practice, Hanover, New Hampshire, in a Special Communication in JAMA Internal Medicine.¹ Acknowledging that the task of providing that information is beset with uncertainty, the authors presented their attempt to “bound this uncertainty by providing a range of estimates—optimistic and pessimistic—on the absolute frequency of 3 outcomes important to the mammography decision: breast cancer deaths avoided, false alarms, and overdiagnosis.”

The optimistic and pessimistic estimates reflect the most and least favorable results of nine randomized trials of screening mammography. Drs. Welch and Passow reported that for every 1,000 women aged 50 screened annually for a decade, an estimated 0.3 to 3.2 will avoid a breast cancer death, 490 to 670 will have at least one false alarm (requiring recall testing, including biopsies), and 3 to 14 will be overdiagnosed and treated needlessly. They also provided estimates for women aged 40 (generally less benefit and greater harm) and women aged 60 (generally greater benefit and less harm).

“Because the risk of false-positive results is considerably lower in other countries and with biennial screening, these data should not be generalized elsewhere,” the authors emphasized. The lower risk of false-positives is partly due to reduced frequency of screening, but “it is more than that,” Dr. Welch told The ASCO Post. “It is because they have a higher threshold for calling a film abnormal.”

Quantified Outcomes for 10 Years

The authors explained that they quantified outcomes for 10 years because it is “long enough for benefit to accrue and short enough to be contemplated by an individual.” They also made the assumption that “a 10-year course of mammography results in mortality reduction extending 15 years. This assumption favors screening because it assumes that the benefit is not delayed at the front end; instead, the reduction in death appears with the first mammogram.” Surveillance, Epidemiology and End Results (SEER) data were used to calculate the risk of dying with and without screening.

The authors resisted the temptation to provide a “best” estimate because “doing so would convey a false sense of certainty and thus be misleading,” they stated.

In a related op-ed piece in The New York Times, Dr. Welch noted that the decision to pursue screening is “a close call.” He continued, “Different people in the same situation can rationally make different choices. But first patients need some quantification of the benefits and harms.”

Changing Attitudes

It has only been in the last decade or so that people have begun to consider the possible harms, as well as the benefits, of screening mammography, Dr. Welch noted. “Part of the cost—and I am talking about human cost, not dollar cost—is that when you look hard for disease, you end up worrying a lot of people unnecessarily about it. And it also leads some people to be treated for a disease that will never bother them. That is the overdiagnosis problem.”

The report noted that the anxiety of false alarms may persist for at least 3 years and produce psychological morbidity. Dr. Welch said there is anecdotal evidence that false alarms can also cause women to become “so frustrated and scared by the process, they want to stop, which can become a major issue” he said.

“One of the most important changes we’ve undergone in the past 10 or 20 years is that advocacy groups for breast cancer have moved from being 100% behind screening to recognizing that there are some limitations, and it is not as simple as it seems on first blush,” Dr. Welch said.

“Some of the women’s advocacy groups are worried that this has created an epidemic of overtreatment and having women excessively worried about their health,” he added. “That is not the road to a healthy society either. So I think there is a recognition that we’ve got to have a better balance.”

Shift to Biennial Screening?

According to the study, decreasing the frequency of screening mammography to every 2 years has been shown to minimize the harm of false-positives and likely also reduces the harm of overdiagnosis.

“The harm it will most clearly affect is the cumulative risk of false-positives,” said Dr. Welch, “but it is a pretty crude way to reduce the rate of false-positives. It doesn’t really change the character of the test; it just reduces a patient’s exposure to it. I would hope in the long run that we would have more sophisticated ways of lowering the false-positive rate.”

Switching to biennial screening might also be expected to lower the rate of preventable deaths, but not by much. “Randomized trial data suggest that the interval between 2 years and 1 year does not have a big effect on preventable death,” Dr. Welch said.

“Reducing the harms of both overdiagnosis and false alarms was the primary motivation behind efforts of the U.S. Preventive Services Task Force (and others) to lengthen the screening interval from annual to biennial,” the article noted. But letters to the editor in response to Dr. Welch’s Times op-ed point out that other organizations continue to adhere to an annual schedule.

“Every medical organization experienced in breast cancer (including the American Cancer Society, American Congress of Obstetricians and Gynecologists, American College of Radiology, Society of Breast Imaging and National Accreditation Program for Breast Centers) recommends annual mammograms for women ages 40 and older,” wrote Barbara Monsees, MD, Chairwoman of the Breast Imaging Commission of the American College of Radiology, and Murray Rebner, MD, President of the Society of Breast Imaging.³

Moving Target

As noted in the JAMA Internal Medicine article, “the better we are at treating clinically evident disease, the less benefit there is to screening.” It has been more than 50 years since the last randomized trial of screening mammography in the United States. “Now that treatment is so much better, how much benefit does screening actually provide? What we need is a clinical trial in the current treatment era,” Dr. Welch wrote in his New York Times op-ed article.

“We have a moving target here, as we always do in medicine. We have an intervention that is done on a massive scale; it literally involves millions of women. It comes with benefits, but it also comes with harms,” Dr. Welch commented in the interview with The ASCO Post. “My coauthor and I have tried to give some sense of the range of effects, and some might be looking at those ranges and saying, ‘There is a lot of imprecision there.’ Maybe we need to have a better idea of what the benefit of mammography is in this current treatment environment, and that would take another randomized trial.”

Two Trials Suggested

Dr. Welch stressed that he knows of no plans or protocols for such trials. In the op-ed, he suggested, “Two randomized trials could begin to answer the central question of mammography interpretation: How hard should the radiologist look? Women who view mammography favorably might be willing to be screened under either the current approach or a high-threshold approach—meaning their radiologist would ignore small, likely harmless abnormalities found on a mammogram. Those who view it less favorably might choose that high-threshold approach (knowing that the harms of false alarms and overdiagnosis would be minimized) or forgo mammography completely,” he wrote.

“Putting the two trials together, we could finally learn what level of screening minimizes false alarms and overdiagnosis while saving the most lives,” he continued. He questioned, however, whether there was the will, interest, or money for such an undertaking. “It is not going to be small, and it is not going to be easy,” he told The ASCO Post.

Disclosure: Dr. Welch reported no potential conflicts of interest.

References

1. Welch HG, Passow HJ: Quantifying the benefits and harms of screening mammography. JAMA Intern Med. December 30, 2013 (early release online).

2. Welch HG: Breast cancer screening: What we still don’t know. New York Times, December 29, 2013.

3. Monsees B, Rebner M: Weighing the value of mammograms. Letter. New York Times, January 2, 2014.