Canadian trial follow up makes controversial mammography claims

An extended follow up of the Canadian National Breast Screening Study (CNBSS) found that annual mammography does not reduce breast cancer mortality for women aged 40-59 beyond what is achieved with usual care and physical examination, according to results published Feb. 11 in the British Medical Journal (BMJ).

However, the American College of Radiology (ACR) and others were quick to point out flaws with the original trial design and said the CNBSS and subsequent follow up analysis of the trial should not be used to set mammography policy.

The CNBSS was a randomized, controlled trial that took place in 15 Canadian screening centers from 1980-1985 and featured nearly 90,000 participants. It was designed to evaluate the benefit of screening mammography versus usual care in women aged 40-49 and also examine the risk and benefits of mammography for women 50-59.

The women in the study were randomly assigned either to receive five annual mammography screens or to a control group with no mammography. Women aged 40-49 in the mammography arm and all women aged 50-59 in both arms also received annual physical breast exams.

Anthony B. Miller, MD, of the University of Toronto, and colleagues sought to reexamine the findings now that study participants had been followed for a mean of 22 years.

They reported that during the five-year screening period, 666 cases of invasive breast cancer were diagnosed in the mammography arm and 524 were diagnosed in the control arm. Of these, 180 women in the mammography arm and 171 women in the control arm died of breast cancer during a follow-up of up to 25 years. Over the entire study period, 3,250 women in the mammography arm and 3,133 in the control arm were diagnosed with cancer, and 500 and 505 died of breast cancer, respectively.

“Thus the cumulative mortality from breast cancer was similar between women in the mammography arm and in the control arm,” wrote Miller and colleagues, who added that the data suggest the value of mammography screening should be reassessed.

The analysis also found that 22 percent of the screen-detected invasive cancers in the mammography arm were over-diagnosed.

Miller and colleagues noted that the findings might not be generalizable to all countries and that early detection could offer greater benefit in areas where cancers are larger at clinical presentation and where there’s a higher proportion of node positive cancers. “However, in technically advanced countries, our results support the views of some commentators that the rationale for screening by mammography should be urgently reassessed by policy makers. Nevertheless, education, early diagnosis, and excellent clinical care should continue to be provided to women to ensure that as many breast tumours as possible are diagnosed at or less than 2 cm.”

In a statement following the publication of the BMJ article, the ACR and the Society of Breast Imaging (SBI) called the analysis misleading and argued that the CNBSS is “deeply flawed and widely discredited.”

According to the ACR and SBI, experts who have reviewed the CNBSS have found that the quality of the mammography was poor and acquired with second-hand machines that were not state-of-the-art at the time of the trial. Grids to remove scatter were not used for much of the trial. Technologists were not taught proper patient positioning and the radiologists involved had no specific training in interpreting mammography. As a result, only 32 percent of cancers in the BMJ paper were detected by mammography alone, when at least two-thirds of cancers should have been detected by mammography alone had they been of higher quality.

The statement also observed that the CNBSS violated protocol for randomized, controlled trials by having study participants evaluated for breast lumps and large lymph nodes before assigning them to the screening or control arms.

“The results of this BMJ study, and others resulting from the CNBSS trial, should not be used to create breast cancer screening policy as this would place a great many women at increased risk of dying unnecessarily from breast cancer,” read the statement.