Background: Idiopathic granulomatous mastitis (IGM) is a chronic breast condition known for its aggressive nature and tendency for persistence and recurrence. Steroids are commonly used as the first-line treatment for IGM, but issues such as the optimal timing, and duration of treatment remain debated. Methods: We retrospectively analyzed 343 IGM cases treated at the Third People’s Hospital of Chengdu from September 2012 to September 2023. Based on inclusion and exclusion criteria, a total of 188 patients were included in the study. Patients were categorized into lump (78 cases), abscess (81 cases), and sinus tract stages (29 cases) according to their initial diagnosis upon admission. Prednisolone was initiated at 0.75 mg/kg/day, and after effective treatment, the dosage was adjusted by 5– 10 mg weekly, followed by a maintenance dose of 2.5– 5 mg/day. Clinical characteristics, treatment responses, adverse effects, recurrence rates, and follow-up data were assessed. Results: The median duration of prednisone treatment in our study was 87 days (range, 21– 281 days). Positive response rates to prednisolone were 78.2% in the lump stage, 60.5% in the abscess stage, and 62.1% in the sinus tract stage. Continuing low-dose prednisone for 3 months post-effective treatment reduced recurrence rates and side effect risks. Weight gain was the most common side effect (39.36%). Conclusion: Early steroid therapy, especially in the lump stage, demonstrated superior efficacy. Following a regimen of starting with a full dose, tapering slowly, and maintaining a low dose for around 3 months steroids treatment is recommended to minimize recurrence rate and adverse effects.

The limited infiltration of CD8+ T cells in tumors hampers the effectiveness of T cell–based immunotherapy, yet the mechanisms that limit tumor infiltration by CD8+ T cells remain unclear. Through bulk RNA sequencing of human tumors, we identified a strong correlation between WNT7A expression and reduced CD8+ T-cell infiltration. Further investigation demonstrated that inhibiting WNT7A substantially enhanced MHC-I expression on tumor cells. Mechanistically, WNT7A inhibition inactivated the Wnt/β-catenin signaling pathway and thus resulted in reduced physical interaction between β-catenin and p65 in the cytoplasm, which increased the nuclear translocation of p65 and activated the NF-κB pathway, ultimately promoting the transcription of genes encoding MHC-I molecules. We found that our lead compound, 1365-0109, disrupted the protein–protein interaction between WNT7A and its receptor FZD5, resulting in the upregulation of MHC-I expression. In murine tumor models, both genetic and pharmaceutical suppression of WNT7A led to increased MHC-I levels on tumor cells, and consequently enhanced the infiltration and functionality of CD8+ T cells, which bolstered antitumor immunity and improved the effectiveness of immune checkpoint blockade therapy. These findings have elucidated the intrinsic mechanisms of WNT7A-induced immune suppression, suggesting that therapeutic interventions targeting WNT7A hold promise for enhancing the efficacy of immunotherapy.

Periductal mastitis (PDM) is characterized by prolonged treatment and high recurrence, yet no large-scale study has identified its recurrence risk factors. A total of 150 treatment-naïve patients diagnosed with PDM at the Third People’s Hospital of Chengdu from January 2019 to March 2025 were retrospectively included. Univariate and multivariate Cox regression analyses were used to identify factors associated with recurrence; Kaplan–Meier and log-rank tests assessed recurrence-free survival. Baseline patient characteristics, along with treatment duration, time to recurrence, and cosmetic outcomes, were systematically recorded. Targeted duct excision was the only independent protective factor against recurrence (adjusted HR = 0.09, 95% CI: 0.04–0.20; p < 0.001). The recurrence rate was 9.0% (7/78) in the excision group versus 70.8% (51/72) in the non-excision group. Median initial treatment duration was shorter (52 [29–73] vs 110.5 [81–145] days; p < 0.001), and among relapsed patients, time from initial treatment end to recurrence was longer (136 [108–159] vs 75 [54–96] days; p < 0.001). Among patients who underwent targeted duct excision, cosmetic outcomes were favorable, characterized by inconspicuous periareolar scars, high patient satisfaction (88.5%), and successful correction of inverted nipples in eligible cases. In patients with PDM, targeted duct excision significantly reduces recurrence risk, shortens treatment duration, and preserves breast appearance, suggesting that this surgical approach should be considered as the primary treatment option for PDM.

Background: GMENA syndrome (granulomatous mastitis, erythema nodosum, with or without arthritis syndrome) is a rare subtype of idiopathic granulomatous mastitis (IGM). However, large cohort studies systematically evaluating its clinical features, response to glucocorticoid therapy, and prognosis are lacking. Methods: This single-center retrospective cohort study included 201 patients diagnosed with IGM at the Third People’s Hospital of Chengdu between January 2014 and January 2026. Among them, 20 patients presented with GMENA syndrome (GMENA group) and the remaining 181 served as the control group. Demographic characteristics, lesion features, laboratory findings, and treatment outcomes were collected for both groups. The two groups were compared regarding glucocorticoid treatment response (early improvement and total treatment duration) and recurrence rate. Results: Compared with the control group, GMENA patients were younger at onset (31–40 years: 80.0% vs. 49.7%, p = 0.01) and had a shorter interval from symptom onset to presentation (85.0% vs. 23.8% presenting within 9 days, p < 0.01). They also exhibited more extensive disease: multiquadrant involvement (100.0% vs. 14.4%), mass size > 3 cm (100.0% vs. 74.0%), multifocal lesions (100.0% vs. 18.8%), and subcutaneous abscess (60.0% vs. 15.5%) (all p < 0.01). All GMENA patients had unilateral involvement. The GMENA group showed a early improvement to glucocorticoids (significant improvement within 1 week: 75.0% vs. 34.8%, p < 0.01), but required a longer treatment duration (>6 months: 65.0% vs. 8.8%, p < 0.01) and had a significantly lower recurrence rate (5.0% vs. 33.7%, p < 0.01). Autoantibody panels were negative in both groups, and no significant difference was found in pus culture positivity rates. Conclusion: GMENA syndrome is a distinct clinical subtype of IGM characterized by acute onset, more severe breast involvement, rapid initial response to glucocorticoids, and, after an adequate prolonged course, favorable long-term outcomes with low recurrence. Early recognition and a treatment strategy of prompt initiation followed by sufficient consolidation are recommended to avoid unnecessary surgery.

Figure S2 Blocking WNT7A leads to an increase in MHC-I expression.

Figure S4 Inhibition of WNT7A leads to the upregulation of MHC-I via the NF-κB pathway.