Idiopathic Granulomatous Mastitis as a Benign Condition Mimicking Inflammatory Breast Cancer: Current Status, Knowledge Gaps and Rationale for the GRAMAREG Study (EUBREAST-15)

Natalia Krawczyk¹, Thorsten Kühn^{2

3}, Nina Ditsch⁴, Steffi Hartmann⁵, Oreste Davide Gentilini⁶, Annette Lebeau^{7

8}, Jana de Boniface^{9

10}, Markus Hahn¹¹, Güldeniz Karadeniz Çakmak¹², Sadaf Alipour^{13

14}, Vesna Bjelic-Radisic¹⁵, Hans-Christian Kolberg¹⁶, Toralf Reimer⁵, Maria Luisa Gasparri^{17

18

19}, Nikolas Tauber²⁰, Melissa Neubacher¹, Maggie Banys-Paluchowski²⁰

Affiliations

¹ Department of Gynecology and Obstetrics, University Hospital Duesseldorf, 40225 Duesseldorf, Germany.
² Department of Gynecology and Obstetrics, University of Ulm, 89070 Ulm, Germany.
³ Department of Gynecology and Obstetrics, Die Filderklinik, 70794 Filderstadt, Germany.
⁴ Breast Cancer Center, University Hospital Augsburg, 86156 Augsburg, Germany.
⁵ Department of Gynecology and Obstetrics, University Hospital Rostock, 18059 Rostock, Germany.
⁶ Department of Breast Surgery, San Raffaele University and Research Hospital, 20132 Milan, Italy.
⁷ Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
⁸ Private Group Practice for Pathology Lübeck, 23552 Lübeck, Germany.
⁹ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 17176 Stockholm, Sweden.
¹⁰ Department of Surgery, Breast Unit, Capio St Göran's Hospital, 11281 Stockholm, Sweden.
¹¹ Department for Women's Health, University of Tübingen, 72076 Tübingen, Germany.
¹² Breast and Endocrine Unit, General Surgery Department, Zonguldak BEUN The School of Medicine, Zonguldak 67600, Türkiye.
¹³ Breast Diseases Research Center, Cancer Institute, School of Medicine, Tehran University of Medical Sciences, Tehran 1419733141, Iran.
¹⁴ Department of Surgery, Arash Women's Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran 1653915911, Iran.
¹⁵ The Breast Unit, Helios University Hospital Wuppertal, University Witten-Herdecke, 42283 Wuppertal, Germany.
¹⁶ Department for Gynecology and Obstetrics, Marienhospital Bottrop, 46236 Bottrop, Germany.
¹⁷ Department of Gynecology and Obstetrics, Ospedale Regionale di Lugano EOC, 6900 Lugano, Switzerland.
¹⁸ Centro di Senologia della Svizzera Italiana (CSSI), Ente Ospedaliero Cantonale, via Pietro Capelli 1, 6900 Lugano, Switzerland.
¹⁹ Faculty of Biomedical Sciences, Università della Svizzera Italiana (USI), via Giuseppe Buffi 13, 6900 Lugano, Switzerland.
²⁰ Department of Gynecology and Obstetrics, University Hospital Schleswig-Holstein Campus Lübeck, 23538 Lübeck, Germany.

PMID: 39410007
PMCID: PMC11476029
DOI: 10.3390/cancers16193387

Review

Idiopathic Granulomatous Mastitis as a Benign Condition Mimicking Inflammatory Breast Cancer: Current Status, Knowledge Gaps and Rationale for the GRAMAREG Study (EUBREAST-15)

Natalia Krawczyk et al. Cancers (Basel). 2024.

. 2024 Oct 3;16(19):3387.

doi: 10.3390/cancers16193387.

Authors

Affiliations

¹ Department of Gynecology and Obstetrics, University Hospital Duesseldorf, 40225 Duesseldorf, Germany.
² Department of Gynecology and Obstetrics, University of Ulm, 89070 Ulm, Germany.
³ Department of Gynecology and Obstetrics, Die Filderklinik, 70794 Filderstadt, Germany.
⁴ Breast Cancer Center, University Hospital Augsburg, 86156 Augsburg, Germany.
⁵ Department of Gynecology and Obstetrics, University Hospital Rostock, 18059 Rostock, Germany.
⁶ Department of Breast Surgery, San Raffaele University and Research Hospital, 20132 Milan, Italy.
⁷ Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
⁸ Private Group Practice for Pathology Lübeck, 23552 Lübeck, Germany.
⁹ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 17176 Stockholm, Sweden.
¹⁰ Department of Surgery, Breast Unit, Capio St Göran's Hospital, 11281 Stockholm, Sweden.
¹¹ Department for Women's Health, University of Tübingen, 72076 Tübingen, Germany.
¹² Breast and Endocrine Unit, General Surgery Department, Zonguldak BEUN The School of Medicine, Zonguldak 67600, Türkiye.
¹³ Breast Diseases Research Center, Cancer Institute, School of Medicine, Tehran University of Medical Sciences, Tehran 1419733141, Iran.
¹⁴ Department of Surgery, Arash Women's Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran 1653915911, Iran.
¹⁵ The Breast Unit, Helios University Hospital Wuppertal, University Witten-Herdecke, 42283 Wuppertal, Germany.
¹⁶ Department for Gynecology and Obstetrics, Marienhospital Bottrop, 46236 Bottrop, Germany.
¹⁷ Department of Gynecology and Obstetrics, Ospedale Regionale di Lugano EOC, 6900 Lugano, Switzerland.
¹⁸ Centro di Senologia della Svizzera Italiana (CSSI), Ente Ospedaliero Cantonale, via Pietro Capelli 1, 6900 Lugano, Switzerland.
¹⁹ Faculty of Biomedical Sciences, Università della Svizzera Italiana (USI), via Giuseppe Buffi 13, 6900 Lugano, Switzerland.
²⁰ Department of Gynecology and Obstetrics, University Hospital Schleswig-Holstein Campus Lübeck, 23538 Lübeck, Germany.

PMID: 39410007
PMCID: PMC11476029
DOI: 10.3390/cancers16193387

Abstract

Background: Idiopathic granulomatous mastitis (IGM) is a rare, benign inflammatory breast condition often mistaken for inflammatory breast cancer and, therefore, requires a biopsy for accurate diagnosis. Although not cancerous, IGM can cause emotional distress because of severe pain and ensuing breast deformity. Differentiating IGM from other breast inflammations caused by infections is essential. IGM mostly affects premenopausal women and is potentially associated with recent pregnancies and breastfeeding. The risk factors, including smoking and contraceptive use, have inconsistent associations. Steroid responses suggest an autoimmune component, though specific markers are lacking.

Methods: We performed a narrative review on potential risk factors, diagnostics, and therapy of IGM.

Results: Diagnostics and clinical management of IGM are challenging. The treatment options include NSAIDs, steroids, surgery, antibiotics, immunosuppressants, prolactin suppressants, and observation, each with varying effectiveness and side effects.

Conclusions: Current IGM treatment evidence is limited, based on case reports and small series. There is no consensus on the optimal management strategy for this disease. The GRAMAREG study by the EUBREAST Study Group aims to collect comprehensive data on IGM to improve diagnostic and treatment guidelines. By enrolling patients with confirmed IGM, the study seeks to develop evidence-based recommendations, enhancing patient care and understanding of this condition.

Keywords: breast inflammation; idiopathic granulomatous mastitis; immunosuppressants; methotrexate; steroids; surgery.

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Conflict of interest statement

Maggie Banys-Paluchowski has received honoraria for lectures and participation in advisory boards: Roche, Novartis, Pfizer, pfm, Eli Lilly, Onkowissen, Seagen, AstraZeneca, Eisai, AstraZeneca, Amgen, Samsung, MSD, GSK, Daiichi Sankyo, Gilead, Canon, Sirius Pintuition, and Pierre Fabre; and study support from Endomag, Mammotome, MeritMedical, Gilead, Hologic, Sirius Medical, ExactSciences. Annette Lebeau declares to have received speaker honoraria and/or personal funds for advisory role from AstraZeneca, Daiichi Sankyo, Gilead, MSD Sharp and Dohme, Myriad Genetics, Novartis, Roche, Menarini Stemline and Veracyte Inc.; writer engagement from QuIP; Steering-Committee Member of Diaceutics and Daiichi Sankyo, Inc. Other authors declare no conflicts of interest.

Figures

**Figure 1**
Typical clinical presentation in patients diagnosed with IGM.

**Figure 2**
Typical sonographic appearance of IGM: (A) heterogeneous mass with ill-defined margins, (B) multiple fluid collections with floating debris.

**Figure 3**
Study flowchart for the prospective data collection phase.

See this image and copyright information in PMC

References

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Idiopathic Granulomatous Mastitis as a Benign Condition Mimicking Inflammatory Breast Cancer: Current Status, Knowledge Gaps and Rationale for the GRAMAREG Study (EUBREAST-15)

Affiliations

Idiopathic Granulomatous Mastitis as a Benign Condition Mimicking Inflammatory Breast Cancer: Current Status, Knowledge Gaps and Rationale for the GRAMAREG Study (EUBREAST-15)

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

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