Background: Prior retrospective studies have evaluated breast MRI in DCIS, and prospective-retrospective biomarker studies have shown that the DCIS Score is prognostic for recurrence after BCS alone. E4112 is a prospective cohort study designed to assess the combined impact of breast MRI and DCIS Score on surgical and RT management. Methods: Women diagnosed with screen-detected DCIS on core biopsy, if BCS eligible, underwent breast MRI. Those remaining so following MRI and related biopsies, with no invasive disease, underwent BCS. If final surgical margins were ≥2 mm, the DCIS lesion was submitted for DCIS Score assay. Women with low DCIS Score (≤39, LS) were advised that RT could be avoided; RT was recommended to those with high/intermediate (H/I) scores. The primary objective was to estimate the fraction converting to mastectomy (Mx) following MRI. Secondary objectives included estimation of re-operation rates after first BCS, and DCIS Score distribution.A sample size of 333 evaluable women would allow estimation of Mx rate of 12% with 95% confidence interval 9-16%. Results: 334 enrolled women had completed surgery; the first surgical procedure was Mx in 54 (16.2%) and BCS in 280 (83.8%), of whom 62 (22.1%) required at least one re-excision, and 11 (3.9%) converted to Mx. DCIS Scores were obtained on 171 patients who completed BCS, of whom 82 were LS and 89 were H/I. Demographics were similar between the two groups, other features will be reported. Only 7/82 (8.5%) of the LS group received RT, whereas 82/89 (92.1%) of the H/I group received RT. Of the 98 BCS patients who did not qualify for DCIS Score-based therapy, 23 had invasive disease, 34 had final surgical margins < 2 mm, and 13 had both. There was insufficient tissue for DCIS Score in 11, and 17 did not complete follow-up. Conclusions: In this study, among DCIS patients who were BCS-eligible following MRI, total mastectomy rate was 19.5%; re-excision rate was 22.1% for women who had BCS. Approximately half had low DCIS Scores, and RT recommendations based on the DCIS Score were acceptable to most women. Clinical trial information: E4112.