GRAnulomatous MAstitis REGistry Study (GRAMAREG)

A Retrospective / Prospective Cohort Study to Evaluate the Incidence, Diagnostic Features, Clinical Course and Treatment Strategies in Histologically Confirmed Idiopathic Granulomatous Mastitis

Idiopathic granulomatous mastitis (IGM) is a rare benign inflammatory breast condition with unknown cause, affecting approximately 2.4 per 100,000 women aged 20-40 years. Patients experience severe local symptoms including pain, redness, and recurrent abscesses that can last weeks to months and often mimic inflammatory breast cancer. Due to its rarity, mostly case reports and case series exist in the literature, leading to limited knowledge about risk factors, optimal treatment strategies, and clinical outcomes.

The GRAMAREG study is the first European registry for patients with histologically confirmed idiopathic granulomatous mastitis. This retrospective/prospective observational cohort study aims to systematically evaluate the incidence, diagnostic features, clinical course, treatment strategies, and patient outcomes of this uncommon disease. The study collects both retrospective data (from January 1, 2015 onwards) and prospective data from participating sites across Europe.

All diagnostic and therapeutic procedures are conducted according to institutional standards in clinical routine, as this is a non-interventional study. Patients in the prospective cohort are followed for up to 5 years to document symptom duration and recurrence rates.

Study Overview

• Status: Not yet recruiting
• Conditions: Idiopathic Granulomatous Mastitis; Granulomatous Mastitis

Detailed Description

Background:

Idiopathic granulomatous mastitis was first described by Kessler and Wolloch in 1972. The etiology remains largely unknown due to its rare occurrence. Valid prevalence data in Europe are lacking, though incidence appears higher in low-income countries compared to Western Europe. IGM predominantly occurs in women of childbearing age, mostly parous and more frequently of non-white ethnicity.

The diagnosis is confirmed only by histological evaluation, typically using core needle biopsy. Patients commonly develop recurrent breast abscesses that do not improve with antibacterial medication and often require repeat incisions or drainages. IGM must be differentiated from granulomatous inflammation associated with duct ectasia, foreign material reactions, specific infections (tuberculosis, fungi, parasites), systemic granulomatous diseases (sarcoidosis), and cystic neutrophilic granulomatous mastitis (CNGM) linked to Corynebacterium species.

Treatment strategies described in literature include high-dose steroids, immunosuppressive agents, bromocriptine, antibiotics, surgical resection, or even mastectomy. However, no evidence-based treatment recommendations are currently available.

Study Design:

This is an investigator-initiated non-interventional observational international prospective/retrospective cohort study with unlimited accrual and open registry duration due to disease rarity.

Data Collection Methods:

Retrospective Phase:

Collection and analysis via anonymized electronic database maintained by EUBREAST e.V. Participating Study Sites identify and document patients with histologically confirmed IGM treated between January 1, 2015, and Study Site activation. No patient identifying information is disclosed or documented. Data are fully anonymous without prospective follow-up.

Prospective Phase:

Patients with histologically confirmed IGM presenting after Study Site activation are informed about possible participation. Written informed consent is obtained. Diagnostic management and treatment follow institutional standards without protocol deviation. Follow-up occurs at 1, 3, and 5 years after first diagnosis to evaluate current symptoms and document potential recurrence.

• Study Type: Observational
• Enrollment (Estimated): 1000

Contacts and Locations

• Study Contact: Name: Natalia Krawczyk, PD Dr. med.; Phone Number: +49 0211 0; Email: Natalia.Krawczyk@med.uni-duesseldorf.de

Study Locations

• Germany
  • North Rhine-Westphalia
    • Düsseldorf, North Rhine-Westphalia, Germany, 40225
      • University Hospital Düsseldorf
      • Contact: Natalia Krawczyk, PD Dr. med.; Phone Number: +49211 81 0; Email: Natalia.Krawczyk@med.uni-duesseldorf.de
  • Schleswig-Holstein
    • Lübeck, Schleswig-Holstein, Germany, 23562
      • Department of Gynecology and Obstetrics University Hospital Schleswig-Holstein
      • Contact: Maggie Banys-Paluchowski, Prof. Dr. med.; Phone Number: +49451 500-41700; Email: Maggie.Banys-Paluchowski@uksh.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients diagnosed with histologically confirmed idiopathic granulomatous mastitis (IGM) or cystic neutrophilic granulomatous mastitis (CNGM) at participating European breast centers and hospitals. The population includes both retrospectively identified patients (diagnosed January 1, 2015, through Study Site activation) and prospectively enrolled patients (diagnosed after Study Site activation). IGM predominantly affects women of childbearing age, mostly parous, and more frequently of non-white ethnicity, though both males and females ≥18 years are eligible.

Description

Inclusion Criteria:

• Histologically confirmed idiopathic granulomatous mastitis OR cystic neutrophilic granulomatous mastitis by local pathology (minimally invasive biopsy or histological confirmation on surgical specimen)
• First histological confirmation after January 1, 2015
• Female or male patients ≥18 years old
• Signed informed consent form for all patients included in prospective part of the study (patients presenting with idiopathic granulomatous mastitis after activation of the study at Study Site)

Exclusion Criteria:

• Patients with suspicion of idiopathic granulomatous mastitis but without histological confirmation
• Suspicion of OR confirmed secondary granulomatous mastitis due to:
• Tuberculosis, Sarcoidosis, Fungal infection, Parasitic infection, Foreign body reaction

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Idiopathic Granulomatous Mastitis Patients; Female and male patients ≥18 years old with histologically confirmed idiopathic granulomatous mastitis (IGM) or cystic neutrophilic granulomatous mastitis (CNGM) diagnosed after January 1, 2015. Histological confirmation obtained by minimally invasive biopsy or on surgical specimen by local pathology. Excludes patients with secondary granulomatous mastitis due to tuberculosis, sarcoidosis, fungal and parasitic infection, or foreign body.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Patients Presenting with Specific Symptoms	Percentage of patients presenting with specific clinical symptoms including pain, redness, and palpable breast mass at initial presentation	At initial diagnosis (baseline)
Duration of Symptoms Depending on Treatment Strategy	Time from initial symptom onset to symptom resolution measured in weeks or months, stratified by treatment approach (systemic treatment, surgical intervention, conservative management)	From initial diagnosis through symptom resolution, up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Type and Duration of Systemic Treatment	Specific systemic treatments received (e.g., corticosteroids, immunosuppressive agents, antibiotics) and duration of each treatment in weeks or months	From initial diagnosis through completion of treatment, up to 5 years
Number of Surgeries Performed	Total number of surgical procedures (incision, drainage, excision, mastectomy) required per patient	From initial diagnosis through 5 years follow-up
Recurrence Rate	Proportion of patients experiencing recurrence of idiopathic granulomatous mastitis after initial treatment	At 1, 3, and 5 years after first diagnosis
Risk Factors Associated with Recurrence	Identification of patient demographics, clinical characteristics, and treatment factors associated with disease recurrence	At 1, 3, and 5 years follow-up
Time to Histological Confirmation	Time interval in days or weeks between first symptom occurrence and first histological confirmation of idiopathic granulomatous mastitis	At baseline (from retrospective chart review or patient recall)
Presentation on Breast Imaging	Imaging characteristics on mammography, sonography, and MRI (if performed) as assessed by the International Steering Committee	At initial diagnosis

Collaborators and Investigators

• Sponsor: European Breast Cancer Research Association of Surgical Trialists

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): April 1, 2031
• Study Completion (Estimated): April 1, 2036

Study Registration Dates

• First Submitted: February 13, 2026
• First Submitted That Met QC Criteria: February 13, 2026
• First Posted (Actual): February 20, 2026

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 26, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Cohort study; Patient registry; Idiopathic granulomatous mastitis; Breast inflammation; Benign breast disease; Granulomatous mastitis; IGM; Cystic neutrophilic granulomatous mastitis; CNGM; Inflammatory breast disease; Chronic mastitis; Non-lactational mastitis; granulomatous lobular mastitis
• Additional Relevant MeSH Terms: Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genetic Diseases, Inborn; Pregnancy Complications; Respiratory Tract Diseases; Digestive System Diseases; Lung Diseases; Infant, Newborn, Diseases; Pancreatic Diseases; Skin Diseases; Breast Diseases; Puerperal Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin and Connective Tissue Diseases; Cystic Fibrosis; Mastitis; Granulomatous Mastitis
• Other Study ID Numbers: EUBREAST-15

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No