Design, implementation, and pitfalls of TMIST.

The early detection of breast cancer has been shown to reduce deaths through randomized, controlled trials. Numerous observational studies, failure analyses, and "incidence of death" studies have confirmed that screening reduces deaths in the general population. Digital Breast Tomosynthesis (DBT) which collects mammographic images from different angles and uses them to synthesize planes through the breast is simply another advance in mammography among others that have been made over the years. DBT "absolutely" detects more cancers at a time when cure is more likely while also having the advantage of reducing recall rates. The Tomosynthesis Mammographic Imaging Screening Trial (TMIST) has been designed to compare DBT with 2-Dimensional Full Field Digital Mammography (FFDM), but it's major design issues may provide misleading results. Instead of using a reduction in deaths as the endpoint, benefit in TMIST is predicated on a reduction in advanced cancers in the DBT group. This is a questionable "endpoint" (a reduction in advanced cancers is not necessary as proof of benefit). In addition, the trial may be underpowered so that even if DBT shows a benefit it may not be able to achieve "statistical significance". The six CISNET models of the National Cancer Institute have shown that annual mammography beginning at the age of 40 will save the most lives. Yet TMIST will only include women ages 45 and over and will screen postmenopausal women every two years instead of annually. Consequently, TMIST results may be used, inappropriately, to limit access to breast cancer screening starting at the age of 45, and only offer biennial screening for post-menopausal women.