This work is presented as a sequence of two parts. In this leading section, a review of the breast tissue-risk research is provided. Although controversy remains, there is substantial evidence indicating that dense mammographic tissue (a) is a breast cancer risk factor that is at least similar, if not greater, in magnitude with the other known breast cancer risk factors and (b) may be a partial biomarker for some of the other risk factors. Understanding these influences may provide a mechanism for measuring the dynamics of breast cancer risk. The totality of this work is to provide support for an automated serial mammography study under way at the authors' institution, where digital mammographic images are acquired with a full-field digital mammography system. This is a filmless imaging system, where the image is acquired in digital format. This electronic imaging acquisition system provides a prime opportunity to easily couple and manipulate the image data with patient information such as risk probability analysis or other pertinent personal history data for improved automated decision making. In this leading section, the main focus is on understanding elements that will assist in fusing risk probability analysis with automated computer-aided diagnosis. The evidence indicates that there are many factors that influence breast tissue at any given time and thus have the ability to alter the associated radiographic image appearance over time. At the initiation of the serial study it was clear that the authors did not fully understand the nature of the problem: automatically comparing similar mammographic scenes acquired at different times. In the second part of this sequence, the more time-related tissue influences are reviewed.