Kate Johnson

December 12, 2013

After standardizing 4 large studies on mammography screening, researchers report that the results are not as disparate as previously believed. All 4 showed a similar substantial breast cancer survival benefit with screening,

This analysis addresses a long-running debate about the value of mammography and the scope of its benefit, said Robert Smith, PhD, senior director of cancer screening at the American Cancer Society in Atlanta.

He spoke at a press conference here at the 36th Annual San Antonio Breast Cancer Symposium (SABCS).

"Typically, people wonder why one organization estimates that you have to screen 2000 women for 10 years to prevent 1 death, and another organization comes up with a much smaller number," Dr. Smith told Medscape Medical News.

"Through standardization, we show that the extreme estimates become less extreme. I hope that by deconstructing these numbers, we can show a more realistic benefit of mammography," he explained.

Before standardization, the analysis showed about a 20-fold difference in estimates of absolute benefit from mammography screening from 4 major reports: the UK Independent Review of Breast Cancer Screening (Br J Cancer. 2013;108:2205-2240), The Nordic Cochrane Review on Screening for Breast Cancer with Mammography (Cochrane Database Syst Rev. 2013;6:CD001877), the US Preventive Services Task Force (USPSTF) review on breast cancer screening (Ann Intern Med. 2009;151:727-737), and the EUROSCREEN (J Med Screen. 2012;19[Suppl 1]:5-13).

The EUROSCREEN study estimated that 90 women need to be screened, with a follow-up of 30 years, to prevent 1 breast cancer death, whereas the Cochrane study estimated that more than 2000 should be screened and followed for 10 years for the same benefit.

But measurements of the effectiveness of mammography screening can vary widely depending on a number of factors, such as the age of the subjects, whether they are simply invited to screening or actually receive screening, and the duration of follow-up.

"Commonly, 30% to 40% of women in these trials never show up to get a mammogram, so the effectiveness measures are biased downward by nonattendance and deaths in the invited group," Dr. Smith explained. "A letter of invitation doesn't do anyone any good. You have to show up for the mammography to benefit from it."

Dr. Smith added that the duration of follow-up is a "critical issue because breast cancer has relatively long survival, even among women who eventually die of their disease." Therefore, "the number needed to screen to prevent 1 cancer death gets increasingly favorable with more years of follow-up, so follow-up of 20 years at a minimum is really critical to begin to see the full benefit of screening."

To reflect these observations, Dr. Smith and his colleagues standardized the results of the 4 studies according to the number of screened patients (rather than those invited), the age of the patients, and the duration of follow-up. The analysis used the UK Independent Review of Breast Cancer Screening as the reference against which the other studies were standardized.

The analysis showed that where there was a previous 20-fold difference between the studies in the estimated number of patients needed to screen to prevent 1 breast cancer death, this disparity between the studies was reduced to a difference of just 2.5-fold.

For example, the Nordic Cochrane review initially used a 10-year screening period followed by a 10-year follow-up period in women 40 to 74 years of age to estimate that 1 breast cancer death could be prevented per 2000 women invited to screening.

After standardization according to actual screenings and a 20-year follow-up in women 50 to 69 years of age, the number of women needed to screen to prevent 1 death fell to 300.

Similarly, the USPSTF estimated that 1339 women 50 to 59 years of age needed to be screened to prevent 1 death; after standardization, this was reduced to 200 to 300.

A similar process with the EUROSCREEN data actually brought the number of women needed to be screened from 90 up to 96.

"Once you standardize to a common population, a common screening scenario, and a common duration of follow-up, these differences become not so significant or important at all, certainly not enough to question the value of mammography," said Dr. Smith.

He added that in discussing the balance of benefit and risk for screening mammography, the biggest downside is clearly overdiagnosis, defined as the detection of a cancer "that never would have arisen symptomatically in a person's lifetime, and never would have been detected if screening had not taken place." Estimates of overdiagnosis with mammography have reached as high as 50%, he reported.

In the process of standardizing estimates, estimates of overdiagnosis must also be adjusted according to lead time and incidence trends, he said.

The standardization process makes sense to quantify the benefit of mammography for early breast cancer detection, said Kent Osborne, MD, codirector of the SABCS and director of the Dan L. Duncan Cancer Center and the Lester and Sue Smith Breast Center at Baylor College of Medicine in Houston. But he added that the need to diagnose breast cancer early may be less urgent than it once was.

"As our treatment of breast cancer improves, it becomes less important to diagnose the cancer early, so the need for mammography and other screening programs declines," Dr. Osborne explained. "We're in a transition; the treatments are getting better, thus the need to diagnose a cancer very early may be a bit less important."

The study was funded by the Centre for Cancer Prevention; the Wolfson Institute of Preventive Medicine; and Barts and The London School of Medicine and Dentistry, Queen Mary University of London. Dr. Smith has disclosed no relevant financial relationships.

36th Annual San Antonio Breast Cancer Symposium (SABCS): Abstract S1-10. Presented December 11, 2013.

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