TMIST Lead-In Randomized Trial of Breast Tomosynthesis Versus Digital Mammography: Results in Women Ineligible for the Full TMIST Trial Due to Age (40-44 or ≥ 75 Years Old).

BACKGROUND. Digital breast tomosynthesis (DBT) has shown improved screening performance compared with digital mammography (DM), although the modality is less well-studied in women 40-44 years old and 75 years and older. OBJECTIVE. The purpose of this study was to compare screening performance between DM and DBT in Tomosynthesis Mammographic Imaging Screening Trial (TMIST) Lead-In trial (A4705) participants who were ineligible for transition to the full TMIST trial (EA1151) due to age at trial entry (40-44 or ≥ 75 years). METHODS. A4705, a prospective trial recruiting women 40 years old and older at four Canadian sites from October 2014 to July 2017, randomized participants to undergo multiple screening rounds by DM or DBT. Final EA1151 eligibility incorporated a narrower age range of 45-74 years. This unplanned analysis included a subset of A4705 participants ineligible for transition to EA1151 due to age at entry (40-44 or ≥ 75 years old). Examination-level screening performance metrics were calculated. The reference standard was determined by 1-year follow-up after participants' last screening round. RESULTS. The study included 271 A4705 participants (mean age, 54 ± 17 [SD] years) who were age-ineligible for EA1151; 181 were 40-44 years old (76 and 105 randomized to DM and DBT, respectively), and 90 were 75 years old or older (46 and 44 randomized to DM and DBT, respectively). Participants in the DM and DBT arms underwent 389 and 482 screening examinations, respectively (mean, 3.2 screening rounds per participant in each arm). Eight cancers were diagnosed (seven screen-detected [one by DM; six by DBT]; one interval cancer in the DBT arm). In participants 40-44 years old, DM, compared with DBT, exhibited a recall rate of 13.2% versus 12.0%, a cancer detection rate (CDR) per 1000 examinations of 0.0 versus 14.6, a PPV1 of 0.0% versus 12.2%, and a PPV3 of 0.0% versus 83.3%, respectively. In participants 75 years old and older, DM, compared with DBT, exhibited a recall rate of 10.1% versus 3.6%, a CDR per 1000 examinations of 7.2 versus 7.1, a PPV1 of 7.1% versus 20.0%, and a PPV3 of 50.0% in both arms. CONCLUSION. Screening performance metrics were overall more favorable for DBT than for DM in women 40-44 years old and 75 years old and older. CLINICAL IMPACT. DBT may mitigate limitations of DM and improve screening performance in the evaluated age groups.