Evaluating the efficacy of topical steroids in idiopathic granulomatous mastitis: a prospective cohort study

Introduction

Idiopathic granulomatous mastitis (IGM) is a rare, benign inflammatory breast disease, with an incidence that has increased significantly in recent years (1). The most common clinical presentation of IGM is a unilateral, painful mass with surrounding induration (2). IGM patients can experience breast abscesses, cutaneous ulceration, and chronic sinus formation, all of which are usually associated with pain, poor breast cosmesis, and a significant negative impact on their quality of life.

Current management strategies for IGM include surgery, oral corticosteroids, antibiotics, Chinese herbal medicine, and close observation (3-6). Among them, oral corticosteroids have played a major role in the treatment of IGM (7,8). However, their long-term use can cause extensive side effects, including obesity, hyperglycaemia, muscle loss, hirsutism, acne, osteoporosis, and hypertension (9). The utility of systemic steroids is thus limited due to their undesirable side effects, especially in young women, who may be particularly reluctant to experience cosmetic adverse effects. A phenomenon known as ’steroid phobia’ is prevalent among women diagnosed with IGM (10). Additionally, patients may experience intolerance during steroid treatment, leading to medication interruptions and ultimately poor clinical outcomes.

IGM is a highly heterogeneous disease. In some cases, it is self-limiting and does not require any treatment (11,12). Currently, we are unable to identify which patients are likely to benefit from conservative treatment. The option of a less aggressive treatment strategy would be beneficial.

Local steroid administration has emerged as an attractive treatment option for IGM. Recent studies have advocated for the local administration of steroids, as this approach can achieve efficacy comparable to oral steroids with fewer side effects (13-16). Current options include intralesional steroid injection or application of topical steroids. Intralesional therapy refers to the direct injection of low-dose corticosteroids around the affected breast tissue. Although effective, its invasive nature and the requirement for multiple physician visits limits its widespread use. Compared to injection therapy, topical steroid treatment is non-invasive and is suitable for long-term treatment. Topical steroid treatment is widely used in inflammatory and allergic skin conditions due to its anti-inflammatory and immunosuppressive properties (17). An international multidisciplinary consensus also provides recommendations for this novel treatment, but evidence supporting its use is limited (18). Due to the rarity of IGM, most reported studies are retrospective and have a limited sample size, resulting in difference of response and recurrence rates for topical steroids (14,19). Thus, well-designed prospective studies need to be conducted to further clarify the therapeutic effects and side effects of topical steroids in the treatment of IGM.

The present prospective cohort study aimed to examine the therapeutic efficacy of topical steroid therapy in the treatment of IGM, and to explore which population is likely to benefit from topical steroids. We present this article in accordance with the STROBE reporting checklist (available at https://gs.amegroups.com/article/view/10.21037/gs-2025-355/rc).

Methods

Study design and participants

This prospective study was conducted at the Breast Surgery Clinic of West China Hospital between January 2022 and October 2024. The study was approved by the Ethics Board of West China Hospital (No. 2022-415) and conducted in accordance with the Declaration of Helsinki and its subsequent amendments. Before enrollment, all patients provided written informed consent to participate and for the publication of their data.

Patients aged 18–65 years diagnosed with IGM by core needle biopsy and were treatment-naïve were eligible for inclusion. Histopathological examination revealed non-caseating granulomas with multinucleated giant cells and chronic inflammatory infiltrates. Patients were excluded if they had been clinically diagnosed with lactating mastitis or breast carcinoma, were pregnant, had a breast abscess, erythema nodosum, a history of previous treatment for IGM, and/or a known allergy to steroids. Patients with granulomatous mastitis secondary to other diseases such as infection, sarcoidosis, polyangiitis, and polyarteritis nodosa were also excluded.

All data, including patient demographics, obstetric history, clinical manifestation, concomitant disease, physical examination (PE), pathological, ultrasound, treatment, and outcome data, were collected and recorded in a prospective standardized case report form (CRF).

Treatment protocol and follow up

Halometasone ointment (0.05%; Aoneng, Bright Future Pharmaceutical Lab. Ltd., Hong Kong, China) was applied to the skin of the affected region of the breast for 1 hour, twice a day, after which any remaining ointment was washed off. A plastic wrap was placed over the cream to promote full absorption. If the initial efficacy evaluation demonstrated partial remission (PR), the current treatment was continued for a further 2 weeks. If there was no significant regression when re-evaluated, the disease was considered stable, and medication continued until complete remission (CR) or the lesion regressed. CR was defined as the complete absence of pain, swelling, erythema and tenderness as well as resolution of breast mass or nodularity on examination or ultrasound after treatment. PR was defined as patient-reported improvement in clinical symptoms, or a reduction of at least 30% in the longest diameter of the mass measured by PE or ultrasound compared to baseline. When disease progressed, characterized by worsening patient-reported symptoms, the emergence of systemic symptoms (e.g., fever, arthritis, erythema nodosum), and/or radiological/clinical evidence of worsening, including a ≥20% increase in lesion size, new lesions, abscess formation, or pronounced local skin redness and swelling, we considered addition or switch to other treatment options. For those with PR but in whom stable breast masses were still present, the use of oral steroids or observation was chosen based on each patients’ preference.

During treatment, patients received regular outpatient clinical visits every 2 weeks. After the treatment was completed, patients received regular follow-up via outpatient clinical visits or telephone calls at 1, 3, and 6 months, and every 6 months thereafter, for a total of 2 years.

Outcomes

The primary endpoints were the response rate (including CR rate and PR rate), and the CR rate. Response to topical steroids was defined as relief in pain, swelling, and erythema, and a decrease in size of the lesion. The secondary endpoints included time to CR, recurrence rate, and time to recurrence. Time to CR was defined as the time interval from treatment initiation to termination due to CR. Relapse was defined as worsening of disease features during the effective treatment or the reappearance of symptoms after the completion of treatment. Breast masses were measured by ultrasonographic assessment.

Statistical analysis

Data was collected and entered in Microsoft Excel, and statistical analysis performed using the software Statistical Package for Social Sciences (SPSS; version 25.0). Continuous variables are expressed as the mean with standard deviation and range. Categorical variables are expressed as the number and percentage. Univariate analysis was conducted on all baseline variables to assess the association between each factor and treatment response. For continuous variables, if the data was normally distributed with homogeneity of variance, an independent Student’s t-test was applied for comparisons; if not, the Mann-Whitney U test was used. For categorical variables, the Chi-squared test or Fisher exact test was employed. A P value of less than 0.05 (two-sided) was considered statistically significant. The sample size was estimated by PASS 15.0 software (test power ≥80%, α=0.05).

Results

A total of 76 patients were enrolled in the study from January 2022 to October 2024 (Table 1). The average age of the patients at the time of diagnosis was 33.2 (range, 16–43) years. A significant number of patients had a history of pregnancy (n=73, 96.1%), childbirth (n=72, 94.7%), or breastfeeding (n=67, 88.2%). Among the patients, 6 (7.9%) had a history of oral contraceptive use, and 1 (1.3%) reported the prior use of psychotropic drugs. One patient developed IGM 2 months after breast lipofilling. Most patients complained of localized symptoms with unilateral breast involvement (n=74, 97.4%), including breast mass (n=76, 100.0%), pain (n=51, 67.1%), skin redness (n=17, 22.4%), axillary node enlargement (n=19, 25.0%), nipple inversion (n=4, 5.3%), and nipple discharge (n=2, 2.6%). Most breast masses were 2 to 5 cm in size (n=57, 75.0%), with 38.2% (29/76) located in the upper external quadrant of the breast. Systemic symptoms were rare, and only 2 (2.9%) patients presented with transient low-grade fever.

Due to loss to follow up, the efficacy of topical steroids could not be evaluated in 6 patients (7.9%), thus, treatment response was evaluated in 70 patients. Among 70 patients treated with topical steroids, 45 patients (64.3%) responded well, while 25 patients (35.7%) were unresponsive to treatment. The overall response rate gradually improved as time progressed (Figure 1). The median time to response was 28 days [interquartile range (IQR), 14–35 days]. Following completion of topical steroid treatment, 23 patients (32.9%) achieved a CR. The median time to a CR was 60 days (IQR, 42–96 days).

Figure 1 Bar chart of the response rates of patients in the study. CR, complete response; PR, partial response.

Compared with the unresponsive patients, those demonstrating a favorable response to topical steroids tended to have a lower rate of breast abscess formation during treatment (35.6% vs. 68.0%; P=0.009). There was no difference between topical steroid treatment responsive and unresponsive patients in terms of age, body mass index (BMI), mass size, bilateral onset, mastitis, and breastfeeding history before disease onset (Table 2).

The study had a median follow-up period of 63 (range, 0–658) days. During the follow-up period, 4 patients (8.9%) experienced recurrent breast mass in the affected side, which was considered a clinical relapse. The medium time to recurrence was 35 days; due to constraints related to sample size, no risk factors for recurrence were identified. Patients with relapse were treated with oral corticosteroids or underwent breast surgery. The main reported adverse effects of topical steroids were local, including erythema (n=6, 8.6%), skin atrophy (n=4, 5.7%), and skin redness (n=2, 2.9%) (Figure 2). No systemic side effects were observed.

Figure 2 Side effects of topical steroid treatment, including erythema (A), skin atrophy (B), and skin redness (C).

Discussion

IGM is a benign inflammatory disorder of the breast with an unknown cause (20,21). There are no consensus guidelines regarding recommended treatment for IGM. Given the heterogeneity of this disease, a treatment that works for all patients is not achievable (22). In current clinical practice, oral steroid therapy is the most widely used first-line medical therapy, however response rates can vary. In our experience, patients newly diagnosed with IGM who receive oral steroids have a response rate exceeding 80% (23). However, long-term and high-dose steroid administration results in numerous side effects, including Cushing’s syndrome, osteoporosis, hyperglycemia, and increased body weight (24,25).

Local steroid treatment is emerging as a feasible option for IGM. In our study, a high response rate (n=45, 64.3%) was observed in patients treated with topical steroids alone, and the CR rate was as high as 32.9%. We have demonstrated that topical steroids represent a feasible alternative to oral steroids in the selected IGM patients. Notably, recurrence was observed in only 4 patients and no steroid-related systemic side effects were detected in the follow up period of 63 (range, 0–658) days. These outcomes suggest that topical steroids can serve as a promising alternative for IGM, especially in cases without breast abscess formation.

Compared with oral steroids, the local application of steroids is associated with lesser systemic absorption, resulting in fewer systemic adverse reactions. Adverse effects when they did occur were limited to local effects, such as skin thinning, atrophy, secondary infections, pigmentation, and capillary dilation, which is consistent with the localized adverse reactions observed in our cohort (26). Local steroid therapy has two primary methods of administration: injection therapy, which involves the direct administration of steroids into the perilesional tissue, and topical application, which involves the external application of a steroid ointment to the surface of the breast. By injecting steroids directly around the lesion, steroids can exert an anti-inflammatory effect at a high local drug concentration, and rapidly alleviate manifestations of IGM (27-29). For deeply located lesions, local steroid injection may have advantages over topical application, as steroids can be directly injected into the vicinity of the lesions. However, as an invasive procedure, local steroid injection has the potential to increase the risk of complications such as bleeding, pain and infection. Additionally, patients receiving injection therapy often require frequent attendance for appointments, which may hinder adherence. Due to its non-invasive nature, the topical application of steroids represents a favorable option for patients as it increases patients’ comfort and compliance.

Our findings confirmed and expand the early observations from small sample size studies on the efficacy of topical steroids for IGM. Gündüz et al. first studied the topical application of steroids to the skin only in the treatment of IGM (19). In their prospective cohort study, 11 IGM patients were treated with topical steroid therapy for 12 weeks. Among them, 9 patients (81.8%) demonstrated a significant reduction in inflammatory manifestations in the affected breasts. After 8 weeks of treatment, the breast skin inflammation completely disappeared without any steroid-related complications. Altintoprak et al. applied prednisone cream (0.125%) topically for a mean duration of 8.2 weeks in 28 patients with IGM, and reported a treatment effectiveness rate exceeding 90% without any side effects (13). The high response rates reported in the above researches were consistent with our results, supporting the efficacy of topical steroids for IGM. The finding by Yildirim et al. that the efficacy of topical steroids was comparable to systemic steroids further supports our results (30). To prevent unnecessary systemic side effects, we preferred to apply topical steroids to small lesions without skin involvement, abscess, or general symptoms. Furthermore, for patients whose IGM progression is controlled by oral steroids, adjunctive topical steroid may be initiated during the phase of weaning oral steroids.

In addition to their use as a primary agent, topical steroids can also serve as an adjuvant treatment for the local management of IGM. Altintoprak et al. reported the successful use of 30 mg/day oral prednisolone combine with twice daily topical prednisolone on 4 days per week (31). Çetin et al. reported no significant difference in the efficacy rates between topical, systemic, and combined therapies (14).

Due to the rarity of IGM, most reported studies are retrospective and have a limited sample size. A major strength of this study is its prospective design and the use of a CRF for systematic data collection, thereby significantly enhancing the reliability of outcomes. However, several limitations must be acknowledged. It is important to note that this study was an observational cohort study without a control group, which prevents definitive conclusions about the relative efficacy of topical steroids. Excluding patients with a breast abscess may affect generalizability, particularly in severe or complicated IGM cases. Given the high heterogeneity of IGM and the absence of standardized treatment protocols, the approach and dosage employed for halometasone in this study were based exclusively on our clinical experience, introducing potential bias in intervention selection. The generalizability of our findings and the identification of risk factors for recurrence is constrained by the limited sample size, an inherent challenge in studying such a rare disease, which warrants a cautious interpretation of the results. The lack of multicenter participation and relatively short median follow-up (63 days) may compromise the external validity and long-term reliability of the findings (e.g., recurrence rates over longer periods).

In summary, topical corticosteroid application demonstrated a promising response rate of 64.3% and a CR rate of 32.9%, indicating the satisfactory management of IGM with halometasone ointment. Our findings provide further evidence supporting the use of topical steroids for selective IGM patients. Our findings suggest this approach should not be employed in patients with a breast abscess due to limited response. High-quality randomized controlled trials need to be conducted to further refine the details of steroid management.

Conclusions

IGM is a rare but locally aggressive disease with a wide range of clinical presentations. In this prospective cohort study, topical steroid therapy emerges as a promising treatment option for IGM, achieving a total response rate of 64.3%. With careful patient selection and close monitoring, topical steroids could be considered as an alternative to oral steroid therapy in the treatment of IGM. Nevertheless, the short-term follow-up duration precludes definitive assessment of long-term outcomes, particularly disease recurrence. Future prospective multicenter randomized trials involving larger patient cohort and extended follow-up periods are warranted to further substantiate the efficacy of topical steroids as a new approach to the management of IGM.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://gs.amegroups.com/article/view/10.21037/gs-2025-355/rc

Data Sharing Statement: Available at https://gs.amegroups.com/article/view/10.21037/gs-2025-355/dss

Peer Review File: Available at https://gs.amegroups.com/article/view/10.21037/gs-2025-355/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-2025-355/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Ethics Board of West China Hospital (No. 2022-415). Before enrollment, all patients provided written informed consent to participate and for the publication of their data.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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(English Language Editor: L. Huleatt)