Abstract Background: Breast cancer exhibits substantial biological heterogeneity, and biopsy-based molecular profiling is limited by cost, sampling error, and inability to capture spatial variability. Breast magnetic resonance imaging (MRI) offers multiparametric assessment of tumor morphology, vascularity, and peritumoral tissue, but its role as a noninvasive biomarker of tumor biology remains underexplored. Methods: We retrospectively evaluated 340 women with invasive ductal carcinoma of no special type or invasive lobular carcinoma who underwent pretreatment 3T breast MRI. Imaging features were classified according to BI-RADS and correlated with histopathological and immunohistochemical markers, including tumor grade, estrogen receptor (ER), progesterone receptor (PR), HER2, Ki-67, and molecular subtype. Multivariable logistic regression was performed, with bootstrap validation and false discovery rate correction. Results: Larger tumors (5 cm) were strongly associated with high grade (74.4%), HER2 positivity (26.8%), elevated Ki-67 (75.0%), and HER2-enriched subtype (14.6%). Paradoxically, round/oval shape and circumscribed margins—features often deemed benign—were predictive of ER/PR negativity, high Ki-67, and triple-negative subtype (OR 3.83, 95% CI 1.48-9.94, P=0.006). In contrast, irregular/spiculated margins correlated with Luminal A tumors and low-grade biology. T2 hyperintensity and peritumoral edema were among the strongest predictors of aggressiveness, independently associated with high grade, lymphovascular invasion, HER2 positivity, and Ki-67 ≥20% (P0.001). Non-mass enhancement patterns were linked to HER2 positivity and intraductal spread, while rim enhancement and washout kinetics identified highly aggressive phenotypes, particularly triple-negative cancers. Multivariable models demonstrated good discrimination (AUC 0.68-0.82). Conclusions: Breast MRI provides robust imaging biomarkers that mirror tumor biology. Morphology, T2 signal, edema, enhancement patterns, and kinetic curves reflect proliferative capacity, receptor expression, HER2 status, and molecular subtype. By integrating imaging with pathology, MRI can enhance risk stratification, capture tumor heterogeneity beyond biopsy, and support precision treatment decisions. These findings highlight MRI as a powerful, noninvasive biomarker with direct translational potential in precision oncology. Citation Format: E. C. Pessoa, H. L. Couto, C. K. C. PESSOA, A. d. Pina, H. D. VESPOLI, D. R. DE PAULA, B. D. A. FILHO, E. A. p. NAHAS. Breast MRI Biomarkers of Tumor Biology: Integrating Imaging with Pathology to Guide Clinical Care abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-06-02.
Pessoa et al. (2026) studied this question.