The 2009 comparative effectiveness review (CER) on the effectiveness of medications to reduce the risk of primary breast cancer in women without preexisting cancer demonstrated the efficacy of two SERMs, tamoxifen citrate (RR, 0.70; 95% CI, 0.59 to 0.82; 4 trials) and raloxifene (RR, 0.44; CI, 0.27 to 0.71; 2 trials). However, the CER also outlined many adverse effects and unknowns about the medications. The objective of this pilot project was to engage stakeholders to develop and prioritize a list of research questions to address the research gaps related to the CER. First, our goal was to provide sufficient detail—including population, intervention, comparator, and outcome (PICO)—for researchers and funders to use in the development of research proposals and solicitations, respectively. Second, this project was intended to identify a feasible and effective approach to identify and prioritize future research from systematic reviews in general.