Mammography screening in women aged 39-49 years: Updated randomized evidence and implications for screening policy.

OBJECTIVE: Mammography screening in women aged 39-49 remains controversial despite evolving guidelines. This study aimed to provide an updated synthesis of randomized clinical trials (RCTs) evaluating the effect of mammography screening on breast cancer (BC) mortality in this group. METHODS: We searched PubMed, Cochrane, and Embase for RCTs assessing the impact of mammography screening on BC mortality in women aged 39-49 years. Data extraction incorporated the most recent follow-up available. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Heterogeneity was evaluated using the I² statistic. Leave-one-out sensitivity analyses were performed to assess robustness. RESULTS: Of 797 records identified, 10 RCTs met the inclusion criteria, encompassing 163,611 women in screening arms and 206,244 in control arms. Median follow-up ranged from 14 to 30 years. The pooled RR for BC mortality was 0.89 (95% CI 0.79-1.01; p = 0.07; I²=24.3%). Exclusion of the CNBSS was the only single-trial omission that yielded a statistically significant reduction in BC mortality with mammography screening (RR 0.85; 95% CI 0.76-0.95; p = 0.005; I²=1.4%). CONCLUSIONS: These findings highlight the need for cautious interpretation of historical randomized evidence when informing screening recommendations for women aged 39-49 years.