We have developed a breast coordinate system that is based on breast anatomy to register female breasts into a common coordinate frame in 2D mediolateral (ML) or mediolateral oblique (MLO) view mammograms. The breasts are registered according to the location of the pectoral muscle and the nipple and the shape of the breast boundary because these are the most robust features independent of the breast size and shape. On the basis of these landmarks, we have constructed a nonlinear mapping between the parameter frame and the breast region in the mammogram. This mapping makes it possible to identify the corresponding positions and orientations among all of the ML or MLO mammograms, which facilitates an implicit use of the registration, i.e., no explicit image warping is needed. We additionally show how the coordinate transform can be used to extract Gaussian derivative features so that the feature positions and orientations are registered and extracted without non-linearly deforming the images. We use the proposed breast coordinate transform in a cross-sectional breast cancer risk assessment study of 490 women, in which we attempt to learn breast cancer risk factors from mammograms that were taken prior to when the breast cancer became visible to a radiologist. The coordinate system provides both the relative position and orientation information on the breast region from which the features are derived. In addition, the coordinate system can be used in temporal studies to pin-point anatomically equivalent locations between the mammograms of each woman and among the mammograms of all of the women in the study. The results of the cross-sectional study show that the classification into cancer and control groups can be improved by using the new coordinate system, compared to other systems evaluated. Comparisons were performed using the area-under-the-receiveroperating- characteristic-curve (AUC) score. In general, the new coordinate system makes an accurate anatomical registration of breasts possible, which suggests its wide applicability wherever 2D mammogram registration is required.