# Predictors of Step-Up Therapy and Outcomes in Idiopathic Granulomatous Mastitis: A Retrospective Cohort Study in Singapore

## TL;DR

This study identifies factors predicting the need for methotrexate in treating a rare breast inflammation and shows it reduces relapses compared to steroids alone.

## Contribution

The paper identifies clinical predictors for methotrexate use in idiopathic granulomatous mastitis and demonstrates its efficacy in reducing relapse rates.

## Key findings

- Oral contraceptive use, smoking, flares, and percutaneous aspiration predict the need for methotrexate in IGM.
- Methotrexate use was associated with lower relapse rates compared to corticosteroids alone.
- Patients on methotrexate had longer time to remission but fewer relapses.

## Abstract

Idiopathic granulomatous mastitis (IGM) is a rare, chronic inflammatory breast disease that often mimics malignancy and carries substantial morbidity. Corticosteroids are the usual first-line treatment, but many patients relapse or develop adverse effects, necessitating escalation to immunomodulatory therapy. In this context, methotrexate, an antimetabolite originally developed for oncology and widely used in autoimmune disorders, represents a promising drug repurposing candidate for IGM. In this study, we identified clinical predictors for requiring methotrexate and demonstrated that its use reduced relapse rates compared to corticosteroids alone. These findings highlight the potential of methotrexate as a therapeutic adjunct to improve outcomes in rare inflammatory breast diseases while minimizing cumulative steroid exposure.

Background: Idiopathic granulomatous mastitis (IGM) is a rare, benign, chronic inflammatory breast condition that poses diagnostic and therapeutic challenges. While corticosteroids are standard first-line therapy, some patients require additional immunomodulation, such as methotrexate. Predictive factors for step-up therapy remain poorly characterized. This study aimed to identify clinical, imaging, and pathological factors predictive of step-up therapy in IGM and evaluate associations between treatment approach and outcomes. Methods: A retrospective cohort study of women diagnosed with IGM was conducted between May 2022 and June 2024 at a tertiary center in Singapore. Data on demographics, clinical presentation, imaging, histopathology, and treatment were extracted. Step-up therapy was defined as methotrexate use following corticosteroids. Primary outcome was predictors of step-up therapy; secondary outcomes included treatment success, relapse, surgery, and time to remission. Statistical analyses included chi-square/Fisher’s exact tests, Cox models, and Kaplan-Meier analysis. Results: Fifty-two women (median age 39 years) were included; 26 (50%) required step-up therapy. Predictors included oral contraceptive (OCP) use (RR 1.92; 95% CI 1.45–2.53; p < 0.001), smoking (RR 2.00; 95% CI 1.49–2.69; p < 0.001), flares (RR 2.33; 95% CI 1.44–3.79; p = 0.002), and percutaneous aspiration (RR 2.10; 95% CI 1.53–2.88; p = 0.025). Patients receiving methotrexate had lower relapse rates (RR 1.23; 95% CI 1.12–1.36; p < 0.001) but longer time to remission (adjusted HR 0.09; 95% CI 0.02–0.46; p = 0.004). Conclusions: OCP use, smoking, flares, and aspiration need may predict step-up therapy in IGM. Early identification could guide a more personalized, potentially top-down treatment.