Idiopathic Granulomatous Mastitis Combination Therapy (IGM-COMBO)

The Effect of the Combination of Excision and Intraoperative Steroid Administration in Idiopathic Granulomatous Mastitis

After breast cancer, diopathic Granulomatous Mastitis (IGM) is among the breast diseases that bother patients and clinicians the most. Countries with a coast to the Mediterranean, especially our country, are the most common geography of this disease. For this reason, a significant part of the important scientific publications about IGM in the last 3-4 decades are from the countries of this geography and mainly from our country. The paradigm of whether IGM should be treated medically or surgically is still a matter of debate. Today, effective treatment results can be achieved with medical treatments, and local drug applications are finding an increasing application area in order to reduce the systemic drug level due to the side effects often seen in this process. As in the centers dealing with breast diseases intensively in our country, patients are treated in our center both by systemic and local means.

Within the body of the Turkish Breast Diseases Federation, after the plans made with the employees of the leading breast centers of the International Breast Health Working Group International planned to start a recording study to observe the activity between, local treatment in the lesion without surgical treatment with systemic treatment in IGM treatment and local treatment together with surgical treatment.

Study Overview

• Status: Recruiting
• Conditions: Idiopathic Granulomatous Mastitis
• Intervention / Treatment: Procedure: Intralesional steroid administration; Procedure: Intraoperative cavity steroid administration

Detailed Description

AIM:

Primary: The effect of the combination of excision and single dose intraoperative steroid administration to the cavity on the shortening of the recovery period in Idiopathic Granulomatous Mastitis.

Secondary: Comparison of the side effects and the relationship between the treatment method and the serum cortisol level in patients treated with intralesional steroid + low dose oral steroid and topical steroid

THE WORK PLAN:

A prospective registry study was designed to compare the effectiveness of the combination of intralesional steroid administration used in the treatment of IGM + low-dose oral steroid therapy used together with the combination of surgical excision and intraoperative intra-cavity steroid administration.

For this purpose, it was planned to observe treatment success rates, time to treatment, recurrence rates at the earliest 1 year follow-up, and side effects related to surgical oral steroid use in eligible IGM patients treated in two different treatment groups.

METHOD:

After clinical and radiological evaluation, histopathological examination will be performed from core biopsy samples taken under ultrasound guidance and tuberculosis (TB) PCR and microbiological culture evaluation will be performed in all patients to rule out specific granulomatous inflammation. Patients with granulmatous inflammation characterized by histopathologically noncaseating granulomas, TB PCR negative and without culture growth, who meet the inclusion criteria, will be recruited into one of the two main treatment arms, at the discretion of the treating centre. There will be no randomization in determining the method of treatment. The type of treatment will be chosen according to the facilities of the performing center, especially the availability of intermittent access to the hospital for non-surgical treatment, and the priority to be determined between the patient and the physician. Since the efficiency superiority between the two methods is not known, any one will not be prioritized and the choice of treatment method will be determined by the patient and the physician. Among these patients, in those with localized abscess type IGM, the abscess foci that are present at the stage of sampling for TB PCR, microbiology culture and histopathology evaluation will be completely aspirated before the treatment is started, and will be waited until the sample results are obtained.

Treatment arms:

Group 1 (NON-SURGERY GROUP): Intralesional steroid + Low dose oral steroid (<30 mg/day prednol) Group 2 (SURGERY GROUP): Excision + Intraoperative steroid injection

Group 1: Patients whose serum cortisol level was observed before starting the treatment, who were injected with 40 mg of prednol at 4 weeks intervals for 3 months for each lesion. The total monthly dose will not exceed 120 mg, and the total 3-month dose will not exceed 200 mg. In this group of patients, the serum cortisol level should have reappeared on the 2nd or 3rd day following each intralesional administration. In this group of patients, low-dose oral prednol (<30 mg/day) and/or topical prednol cream can be applied twice a day during the treatment.

In patients included in Group 2, serum cortisol levels should have been observed before starting treatment. Then the patients should be operated and the mass(s) should be excised. Intraoperatively, not less than 40 mg of prednol should be injected into each mass cavity (it may vary according to the cavity diameter), and the amount applied to all cavities should not exceed 200 mg in total. The amount of prednol administered for each cavity should be recorded. In this group of patients, prednol may have been administered to the cavity walls (Group 2a) or inside the cavity (Group 2b). Serum cortisol levels should be seen in patients 7 to 10 days after the procedure.

Group 2a: 4 Quadrants 40 mg predmol per cavity wall (for < 2 cm lesion and an additional 20 mg for each additional 1 cm) Group 2b: 40 mg predmol into the cavity (for < 2 cm lesion and an additional 20 mg for each additional 1 cm)

Monitoring parameters:

• Recovery rates
• Time to recovery
• Recurrence rates after one-year follow-up
• Complications / side effects due to surgery or oral steroid use
• Relationship between steroid administration method and serum cortisol level Recovery (remission) was defined as the complete disappearance of pre-treatment clinical and ultrasonographic mastitis findings for patients in Group 1, and completion of wound healing for patients in Group 2.

Relapse was defined as the clinical or ultrasonographic re-detection of the disease in the same breast in both groups, following remission, in a similar or different type to the pre-treatment. Any need for repetitive surgery in the surgical arm will also be considered a recurrence.

In case of relapse in patients in both groups, the continuation of treatment will be left to the choice of centers.

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ozgur Aytac, MD; Phone Number: 905326529343; Email: oaytac@gmail.com
• Study Contact Backup: Name: Mehmet A Mazlı, MD; Phone Number: 05327346195; Email: mnazli46@yahoo.com

Study Locations

• Turkey
  • Yuregir
    • Adana, Yuregir, Turkey, 01120
      • Recruiting
      • Baskent University Adana Teaching Hospital
      • Contact: Ozgur Aytac, MD; Phone Number: 5326529343; Email: oaytac@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Patients diagnosed with IGM histopathologically
• Patients in groups A, B and C according to clinical classification
• Ultrasonographically; Patients with leaf-like hypoechoic type, localized abscess type, and localized hypoechoic mass type mastitis

Exclusion Criteria:

• Patients diagnosed with tumor after biopsy
• Those with TB PCR (+)
• Presence of clinically widespread abscess and cellulite (group D patients)
• Ultrasonographically; diffuse diffuse type
• Pregnancy
• Breastfeeding period

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: NON-SURGERY GROUP; Group 1: Patients whose serum cortisol level was observed before starting the treatment, who were injected with 40 mg of prednol at 4 weeks intervals for 3 months for each lesion. The total monthly dose will not exceed 120 mg, and the total 3-month dose will not exceed 200 mg. In this group of patients, the serum cortisol level should have reappeared on the 2nd or 3rd day following each intralesional administration. In this group of patients, low-dose oral prednol (<30 mg/day) and/or topical prednol cream can be applied twice a day during the treatment.	Procedure: Intralesional steroid administration; Treatment by administering steroids into the lesion
Active Comparator: SURGERY GROUP; In patients included in Group 2, serum cortisol levels should have been observed before starting treatment. Then the patients should be operated and the mass(s) should be excised. Intraoperatively, not less than 40 mg of prednol should be injected into each mass cavity (it may vary according to the cavity diameter), and the amount applied to all cavities should not exceed 200 mg in total. The amount of prednol administered for each cavity should be recorded. In this group of patients, prednol may have been administered to the cavity walls (Group 2a) or inside the cavity (Group 2b). Serum cortisol levels should be seen in patients 7 to 10 days after the procedure. Group 2a: 4 Quadrants 40 mg predmol per cavity wall (for < 2cm lesion and an additional 20 mg for each additional 1 cm) Group 2b: 40 mg predmol into the cavity (for < 2 cm lesion and an additional 20 mg for each additional 1 cm)	Procedure: Intraoperative cavity steroid administration; Treatment by administering steroids into the surgical cavity

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The effect of excision and intraoperative steroid administration to the cavity in Idiopathic Granulomatous Mastitis.	The effect of the combination of excision and single dose intraoperative steroid administration to the cavity on outcome in Idiopathic Granulomatous Mastitis.	one year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of side effects in patients who received intralesional steroid	Comparison of side effect rates in patients treated with intralesional steroids +/- low-dose oral steroids and/or topical steroids.	one year
Correlation of treatment modality and serum cortisol levels.	Correlation of treatment modality and serum cortisol levels in patients treated with intralesional steroids +/- low-dose oral steroids and/or topical steroids.	one year

Collaborators and Investigators

• Sponsor: Baskent University
• Investigators: Study Director: Ozgur Aytac, MD, Başkent University

Publications and helpful links

General Publications

• Hu T, Li S, Huang H, Huang H, Tan L, Chen Y, Deng H, Wu J, Zhu L, Zhang J, Su F, Chen K. Multicentre, randomised, open-label, non-inferiority trial comparing the effectiveness and safety of ductal lavage versus oral corticosteroids for idiopathic granulomatous mastitis: a study protocol. BMJ Open. 2020 Oct 10;10(10):e036643. doi: 10.1136/bmjopen-2019-036643. Erratum In: BMJ Open. 2022 Aug 25;12(8):e036643corr1.
• Ma X, Min X, Yao C. Different Treatments for Granulomatous Lobular Mastitis: A Systematic Review and Meta-Analysis. Breast Care (Basel). 2020 Feb;15(1):60-66. doi: 10.1159/000501498. Epub 2019 Jul 10.
• Zhou F, Liu L, Liu L, Yu L, Wang F, Xiang Y, Zheng C, Huang S, Cai H, Yu Z. Comparison of Conservative versus Surgical Treatment Protocols in Treating Idiopathic Granulomatous Mastitis: A Meta-Analysis. Breast Care (Basel). 2020 Aug;15(4):415-420. doi: 10.1159/000503602. Epub 2019 Oct 22.
• Wang Y, Song J, Tu Y, Chen C, Sun S. Minimally invasive comprehensive treatment for granulomatous lobular mastitis. BMC Surg. 2020 Feb 22;20(1):34. doi: 10.1186/s12893-020-00696-w.

Study record dates

Study Major Dates

• Study Start (Actual): April 16, 2022
• Primary Completion (Anticipated): April 1, 2023
• Study Completion (Anticipated): September 1, 2023

Study Registration Dates

• First Submitted: April 27, 2022
• First Submitted That Met QC Criteria: May 3, 2022
• First Posted (Actual): May 5, 2022

Study Record Updates

• Last Update Posted (Actual): May 5, 2022
• Last Update Submitted That Met QC Criteria: May 3, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Steroid injection; Topical steroid; Idiopathic granulomatous mastitis; Steroid injection to surgical cavity
• Additional Relevant MeSH Terms: Skin Diseases; Breast Diseases; Pregnancy Complications; Puerperal Disorders; Mastitis; Granulomatous Mastitis
• Other Study ID Numbers: MF 22-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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