Background: It is assumed that most locally advanced breast cancers (LABC) could be detected at an earlier stage with routine screening. However, LABCs may present between screens as interval cancers (IC). ICs present at an earlier age, with higher grade, larger size, and are associated with lower survival, compared to screen-detected cancers (SDC), and comprise 17% of cancers from population-based screening programs. We evaluated the screening history in patients with LABCs from the I SPY TRIAL, to determine the frequency of screening and ICs. Methods: Of 221 pts enrolled in the I-SPY TRIAL, a multisite neoadjuvant study for women with LABCs > 3cm in size, screening history and presentation were retrospectively collected for 154. Two groups, screened (S), defined as a mammogram within 2 years, or non screened (NS), previous mammogram more than 2 years prior, were evaluated (Table). The frequency of ICs at 1 and 2 years was determined in S pts. Frequency of mammographically occult (MO) tumors was determined for all. Results: Of the total, 99 (64%) and 55 (36%) were NS and S, respectively. Mean tumor size for all pts was 6.7cm. Only 11 (20%) of S pts were SDCs and 44 (80%) were ICs, with 24 (63%) diagnosed within 1 year and 14 (37%) between 1 and 2 yrs of their last normal mammogram. 24 (24%) NS patients were younger than the recommended screening age of 40; in the remaining 75 pts, 9 (12%) were MO. Only 20% of IC tumors were MO. ICs were of higher grade (44% vs 11% grade III), and tumor size (7.0cm vs 4.4cm) than their SDC counterparts. 80% of cancers detected in I SPY were NKI70 gene test poor prognosis. Relationship to breast density and subtype is currently being assessed. Conclusions: Women presenting with LABCs have a high likelihood (80%) of an IC. This suggests that the growth rate of LABCs precludes early detection by conventional screening. Understanding the biology of ICs will be important to develop better strategies for prevention and early detection.