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 ≥ 74 Years Old).

Background: Digital breast tomosynthesis (DBT) has shown improved screening performance compared to digital mammography (DM), although the modality is less well-studied in women 40-44 or ≥75 years old. Objective: 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 old). Methods: A4705, a prospective trial recruiting women ≥40 years old 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 years) 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 (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 (7 screen-detected 1 by DM; 6 by DBT; one interval cancer in DBT arm). In participants 40-44 years old, DM, compared with DBT, exhibited recall rate of 13.2% versus 12.0%, cancer detection rate (CDR) per 1000 of 0.0 versus 14.6, PPV1 of 0.0% versus 12.2%, and PPV3 of 0.0% versus 83.3%, respectively. In participants ≥75 years old, DM, compared with DBT, exhibited recall rate of 10.1% versus 3.6%, CDR per 1000 of 7.2 versus 7.1, PPV1 of 7.1% versus 20.0%, and 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 or ≥75 years old. Clinical Impact: DBT may mitigate limitations of DM and improve screening performance in the evaluated age groups.