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Breast cancer death rates in the U.S. have decreased in recent decades, however areas such as Appalachia with fewer cancer care resources may not have experienced comparable mortality declines. This study examines trends in breast cancer mortality rate disparities in Appalachian states and the continental U.S. using data from SEER mortality files 1969-2007 and the Area Resource File. Overall breast cancer mortality rates decreased significantly, with a smaller decline in Appalachian counties (17.5%) compared with non-Appalachian counties in Appalachian states (30.5%), and compared with non-Appalachia U.S. counties (28.3%). After accounting for poverty, rural/urban status, education, health care resources, and proportion White in the population, residence in Appalachian counties except for those in the Northern subregion was significantly associated with smaller reduction in breast cancer mortality rates. Lower levels of education, physician density, and percent White in the population were also associated with smaller reductions in breast cancer mortality.