Based on a 25 year follow-up data study from a Canadian screening facility, yearly mammography failed to diminish breast cancer mortality rates in women ages 40 to 59, as opposed to physical examination or standard care.
Women screened on an annual basis by mammography for 5 years had had a breast cancer mortality propensity of 1.05 as opposed to the control group during the screening period. During follow-up for an average of 22 years, the mammography group had a breast cancer mortality propensity of 0.99 compared to the control group. However, neither value was statistically significant.
Following 15 years of follow-up, the mammography group had a surplus of 106 breast cancers associated to overdiagnosis, as reported in BMJ Open.
"Although the difference in survival after a diagnosis of breast cancer was significant between those cancers diagnosed by mammography alone and those diagnosed by physical examination screening, this is due to lead time, length of time bias, and overdiagnosis," Anthony B. Miller, MD, of the University of Toronto School of Public Health, and colleagues said of their findings.
"At the end of the screening period, an excess of 142 breast cancers occurred in the mammography arm compared with the control arm, and at 15 years, the excess remained at 106 cancers. This implies that 22% (106 of 484) of the screen-detected cancers in the mammography arm were overdiagnosed. The findings suggest a need to reassess the value of screening mammography,” they added.
The publication garnered a swift and strong response from the American College of Radiology (ACR) and the Society of Breast Imaging (SBI). In a shared statement, officials of the two organizations described the results as "an incredibly misleading analysis based on the deeply flawed and widely discredited Canadian National Breast Screening Study (CNBSS)."
Taking into account that the 32% rate of cancer detection by mammography, the ACR and SBI said "this extremely low number is consistent with poor-quality mammography. Mammography alone should detect twice that many cancers,” they added. The organizations mentioned that a former outside review of the CNBSS verified the poor quality of mammography in the study.
The joint statement also called the randomization process used by CNBSS into question, highlighting that all women had a clinical breast examination prior to allocation, providing investigators with advance knowledge about which patients had breast lumps or enlarged lymph nodes.
“The findings should come as no surprise,” said Richard C. Wender, MD, of the American Cancer Society (ACS). “The CNBSS has been an "outlier" from the initial report, and the lack of benefit with mammography wouldn't be expected to change with additional follow-up.”
Miller and colleagues reported 25-year follow-up data from the CNBSS, which started in 1980. All women, ages 50 to 59, had yearly clinical breast examinations, as did women 40 to 49 in the mammography arm. Younger women in the control arm had a clinical breast exam at enrollment, followed by standard care.
The study included 89,835 women registered at 15 centers in six Canadian provinces. During the 5-year mammographic-screening period, 666 invasive cancers were diagnosed in the mammography arm and 524 in the control group. Moreover, 180 women randomized to mammography died of breast cancer, as did 171 in the control group.
The hazard ratio (HR) for breast cancer-specific mortality during the screening period was 1.05 for mammography compared to control.
During the whole study, 3,250 women in the mammography group developed breast cancer as opposed to 3,133 in the control group, and 500 breast cancer deaths occurred in the mammographically screened patients as opposed to 505 in the control group, leading to an HR of 0.99.
The authors of an accompanying editorial noted that some evidence suggests that improved treatment, rather than breast cancer screening, has propelled the decline in breast cancer mortality in recent years. Regardless of the rates found in different studies, overdiagnosis represents a larger problem.
"The real amount of diagnosis in current screening programs might be even higher than that reported in the Canadian study, because ductal carcinoma in situ, which accounts for one in four breast cancers detected in screening programs, was not included in the analysis. We agree with Miller and colleagues that 'the rationale for screening by mammography be urgently reassessed by policymakers," said Mette Kalager, MD, of the University of Oslo in Norway, and colleagues.
In a response to the ACR/SBI comments, Miller called the statement "deeply flawed and misleading, as it ignores all our previous clarifications on the issues raised."
To the claim of poor mammographic quality, Miller said “the study demonstrated an excellent cancer detection rate, participating centers used modern (for the time) imaging machines, and technologists were trained in accordance with prevailing standards for North America.”
"The randomization in the trial was assessed by two internationally recognized epidemiologists and was deemed to comply fully with accepted standards," Miller added in an e-mail. "Other commentators have agreed and regarded our study as high quality."
In planning the trial, researchers overestimated the number of breast cancer deaths that would occur, a reflection of the care the patients received.
"We had to postpone our first definitive analysis for 2 years so that sufficient events would accumulate. However, our long-term follow-up has resulted in sufficient events so that we can state with a high degree of confidence that mammography screening does not result in a reduction of breast cancer mortality,” said Miller.
In direct reference to the ACR and SBI, Miller said the study's outcome "has to be unwelcome to this highly financially conflicted group, but which will be of substantial interest to policy makers in considering the future of screening for breast cancer."
Recognizing the powerful emotions essential viewpoints on mammography, Wender said the issues will continue to be debated. ACS plans to review its mammography recommendations this year, and the United States Preventive Services Task Force (USPSTF) has implied that a panel may review the organization's recommendations later this year.
"My own sense is that we did not learn a lot from the Canadian study. These numbers have been out for a long time. Maybe the one new thing we learned is that if you go out 25 years, the number of cases in the screening and control groups were pretty similar,” said Wender.
A main issue often gets overlooked or lost in the debate over statistics and methodology.
"There is unanimity of opinion among the major guidelines groups that attempt to synthesize all of the data. That is, mammography reduces age-adjusted mortality rates. It does avert/prevent premature breast cancer death, not just in women over 50 but in women in their 40s. Ultimately, the guideline groups are charged with balancing the benefits and risks of screening, and there is no perfect way to do that,” said Wender.
As of now the final word on the issue according to Wender is that the ACS and USPSTF recommendations, possibly the best known in the U.S., are more similar than different. "I think we all look at the differences."