Foundation model embeddings capture pre-diagnostic changes on screening mammograms

Foundation model embeddings of screening mammograms may encode pre-diagnostic tissue change without task-specific adaptation. We tested whether embeddings move faster along a data-derived "cancer direction" in women later biopsied for cancer than in matched screen-negative controls, and whether this depends on pretraining domain. We studied 1,773 biopsied women (785 malignant, 988 biopsy-negative) and 1,773 matched controls, each with at least two annual screening exams before their index exam. An identical pipeline was applied to four 2D models: Mammo-CLIP (MC, out-of-distribution mammography), HOPPR (in-distribution mammography), MedImageInsight (MII, general medical imaging), and BiomedCLIP (biomedical vision-language pretraining on literature figures). Breast-level embeddings quantified longitudinal movement along the cancer direction. We compared cases and controls using a between-patient design with complementary mixed-effects analysis, and biopsied versus healthy contralateral breasts within patients. Under matched modality in MII embedding space, malignant cases drifted significantly faster than controls in the first two screening intervals preceding the index exam; biopsy-negative cases showed significance only in the first. MC differences were significant in the first interval for both biopsy groups. Within-patient comparisons showed a broadly similar pattern, with MC significance extending to the second interval in both groups and HOPPR showing significance at interval 1. BiomedCLIP showed no significant differences in either design or biopsy group. Overall, directional embedding velocity emerges as a property of clinically grounded rather than general biomedical pretraining, showing that foundation model embeddings can encode pre-diagnostic mammographic change without task-specific adaptation.