Large trial, long follow-up are key strengths
The UK Age trial’s primary strength is its study design: a large population-based RCT that included diverse participants with the critical study outcome for cancer screening (mortality). The study’s long-term follow-up is another key strength, since breast cancer mortality typically occurs 7 to 10 years after diagnosis. In addition, results were available for 99.9% of the women enrolled in the trial (that is, only 0.1% of women were lost to follow-up). Interestingly, the demonstrated mortality reduction with screening mammography for women in their 40s validates the mortality benefit demonstrated in other large RCTs of women in their 40s.1
Another strong point is that the study addresses the issue of whether screening women in their 40s results in overdiagnosis compared with women who start screening in their 50s. Further, this study validates a prior observational study that mammographic findings of nonprogressive cancers do not disappear, so nonaggressive cancers that present on mammography in women in their 40s still would be detected when women start screening in their 50s.8
Study limitations should be noted
The study has several limitations. For example, significant improvements have been made in breast cancer treatments that may mitigate against the positive impact of screening mammography. The impact of changed breast cancer management over the past 20 years could not be addressed with this study’s design since women would have been treated in the 1990s. In addition, substantial improvements have occurred in breast cancer screening standards (2 views vs the single view used in the study) and technology since the 1990s. Current mammography includes nearly uniform use of either digital mammography (DM) or digital breast tomosynthesis (DBT), both of which improve breast cancer detection for women in their 40s compared with the older film-screen technology. In addition, DBT reduces false-positive results by approximately 40%, resulting in fewer callbacks and biopsies. While improved cancer detection and reduced false-positive results are seen with DM and DBT, whether these technology improvements result in improved breast cancer mortality has not yet been sufficiently studied.
Perhaps the most important limitation in this study is that the women did not undergo routine risk assessment before trial entry to assure that they all were at “average risk.” As a result, both high- and average-risk women would have been included in this population-based trial. Without risk stratification, it remains uncertain whether the reduction in breast cancer mortality disproportionately exists within a high-risk subgroup (such as breast cancer gene mutation carriers).
Finally, the cost efficacy of routine screening mammography for women in their 40s was not evaluated in this study.
The UK Age trial in perspective
The good news is that there is the clear evidence that breast cancer mortality rates (deaths per 100,000) have decreased by about 40% over the past 50 years, likely due to improvements in breast cancer treatment and routine screening mammography.9 Breast cancer mortality reduction is particularly important because breast cancer remains the most common cancer and is the second leading cause of cancer death in women in the United States. In the past decade, considerable debate has arisen arguing whether this reduction in breast cancer mortality is due to improved treatments, routine screening mammography, or both. Authors of a retrospective trial in Australia, recently reviewed in OBG Management, suggested that the majority of improvement is due to improvements in treatment.3,10 However, as the authors pointed out, due to the trial’s retrospective design, causality only can be inferred. The current UK Age trial does add to the numerous prospective trials demonstrating mortality benefit for mammography in women in their 40s.11
What remains a challenge for clinicians, and for women struggling with the mammography question, is the absence of risk assessment in these long-term RCT trials as well as in the large retrospective database studies. Without risk stratification, these studies treated all the study population as “average risk.” Because breast cancer risk assessment is sporadically performed in clinical practice and there are no published RCTs of screening mammography in risk-assessed “average risk” women in their 40s, it remains uncertain whether the women benefiting from screening in their 40s are in a high-risk group or whether women of average risk in this age group also are benefiting from routine screening mammography.
Continue to: What’s next: Incorporate routine risk assessment into clinical practice...