OBJECTIVES: The association between treatment advances and dissemination and the cost-effectiveness of cancer screening is largely unknown. This study addressed the above association among breast cancer patients. METHODS: Using a Bayesian microsimulation model, we followed a hypothetical cohort of 1 million women born in 1960 throughout their lifetimes. We compared no screening strategy to eight mammography screening strategies that consisted of a combination of different initiation age (40 vs. 50), cessation age (74 vs. 79), and frequency (annual vs. biennial) of screening. Upon identifying the most cost-effective strategy, we then applied probabilistic sensitivity analyses (PSA) to explore the impact of different patterns of treatment dissemination on the cost-effectiveness of screening. RESULTS: At the societal willingness-to-pay (WTP) of $50,000 per life year (LY) gained and with the dissemination pattern prior to the availability of trastuzumab, the most cost-effective screening strategy was biennial screening for women aged 50-74. The probability that this strategy was more cost-effective than the no screening strategy was 0.43, followed by biennial screening 50-79 (prob=0.41), biennial screening 40-79 (prob = 0.08), and biennial screening 40-74 (prob = 0.04). At a WTP of $100,000/LY, the probabilities increased to 0.89, 0.87, 0.76, and 0.72, respectively. Results from the PSA indicated that when adding trastuzumab to the base case dissemination pattern, the probability that the biennial screening 50-74 strategy was more cost-effective than the no screening strategy at a WTP of $100,000/LY decreased from 0.89 to 0.83, and the probability further reduced to 0.60 if the optimal dissemination pattern (e.g., all patients with HER2 overexpression received trastuzumab) was achieved.  CONCLUSIONS: The finding that improvements in treatment dissemination may paradoxically lead to a reduction in the cost-effectiveness of screening suggests that identifying and designing cost-effective strategies to allocate health care resources across the continuum of cancer care is likely to yield higher gains.