Abstract Background: As mammography is not generally recommended to women under 40, it is reasonable to conclude that documented outcome improvements over time are attributable to treatment advances with screening playing a less important role. In order to determine the contribution of screening and treatment to improvements, we evaluated the odds of presenting with more advanced disease by time-period and examined the time-trends in outcome in a population-based cohort ≤50. We evaluated whether any outcomes differentials existed by ER status. Methods: Patients in SEER diagnosed with breast cancer (BC) were divided into 4 by year of diagnosis (1990–1994, 1995–1999, 2000–2004, 2005–2008). Patients were also categorized into 2 age-groups: <40 and 40–50 years. Odds ratios for presenting with more advanced disease over the 4 time-periods were calculated for the 2 age-groups. Multivariate analysis was done to investigate the association of survival with time-period for the 2 age-groups by ER status. Results: 110,629 patient records were included. Multivariate adjusted hazard ratio for mortality in women aged 40–50 with ER positive BC declined over time. Comparing all time periods to 1990–1994, the HR for mortality in 1995–1999 was 0.83 (0.77–0.89), 0.61 (0.57–0.65) in 2000–2004, and 0.35 (0.30–0.40) in 2005–2008 (p <.001). Those <40 years with ER positive BC also had mortality improvements over time (HR 0.86, 0.63, 0.26 for 1995–1999, 2000–2004, and 2005–2008 respectively). On the contrary, no mortality improvements were seen in women with ER negative disease. Trends in progressively worsening mortality over time were observed in this cohort. A 1.3-fold increase in the odds of presenting with stage I BC was seen in women 40–50 years comparing the 3 latter time periods with 1990–1994. Similarly, in the same age group, there was a 2.12-fold likelihood of presenting with a tumor ≤1cm in 2005–2008 versus 1990–1994. In women <40 years at diagnosis, the probability of presenting with stage I disease was lower in the 3 latter time periods than in 1990–1994; and a 2.84-fold higher probability of presenting with stage III/IV disease was seen in 2005–2008 compared with 1990–1994. Conclusions: Patients who are ER positive and between 40–50 years have had time-trend changes with improvements in breast cancer outcome and smaller tumors likely attributable to both screening and hormonal therapies. Patients who are <40 years and/or ER negative have not had improvements in breast cancer outcome. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-07-02.