Abstract Background: Granulomatous mastitis (GM) is a rare, benign inflammatory breast condition primarily affecting parous, reproductive-aged women. However, Hispanic and African American women are disproportionately affected. As GM can mimic malignant breast disease, it remains a diagnostic and therapeutic challenge, especially in the absence of standardized treatment guidelines. Methods: A single-institution, retrospective review of all cases of GM sequentially captured from January 2024 to March 2025 at a minority-serving breast clinic. A total of 4 patients were included in the study. Results: All four patients initially presented with breast pain, swelling, and masses concerning for malignancy based on clinical findings and imaging. Biopsies in each case confirmed granulomatous mastitis without evidence of malignancy. Antibiotics and steroids provided partial or temporary relief in three patients, but recurrent or persistent disease led to the application of disease-modifying antirheumatic drug therapy with methotrexate (MTX). Notably, all patients had a negative rheumatologic workup. Conclusions: This series illustrates the varied clinical spectrum of GM and underscores the importance of a timely biopsy to differentiate it from carcinoma, particularly in women of color. Notably, our case series suggests that early MTX initiation can be valuable, particularly in patients with persistent or recurrent disease despite antibiotics and corticosteroids, which could reduce morbidity and avoid prolonged surgical interventions. Prospective studies are needed to further clarify the role of early MTX in GM management and to establish standardized treatment protocols. Citation Format: A. M. Otieno, D. Dewar, T. Haroun, Q. Chu, S. Nagel, M. Tee, R. Williams. Case Series on Early Methotrexate Use in Reducing Morbidity in Granulomatous Mastitis 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 PS5-06-06.
Otieno et al. (Tue,) studied this question.