Coexisting Granulomatous Mastitis and Breast Cancer: A Systematic Review

Abstract Introduction: Granulomatous mastitis (GM) is a rare inflammatory breast disease that mimics carcinoma. GM can coexist with breast cancer (BC), though the relationship remains unclear. This systematic review aims to examine the coexistence of GM and BC, focusing on the clinicopathological features of synchronous and metachronous cases. Methods: A systematic search of PubMed/MEDLINE and Google Scholar, up to the 30th November 2025, identified studies reporting individual patient-level data. Inclusion criteria were: (1) patients diagnosed with both BC and GM (concurrently or sequentially); (2) histopathological or imaging confirmation of both conditions. Exclusion criteria were: (1) animal studies; (2) conference abstracts; (3) non-recommended journal publications; and (4) non-English papers. Descriptive statistics were used to summarize categorical variables as frequencies and percentages, and continuous variables as means or medians with ranges. Results: Nineteen studies (23 female patients; median age of 42 years) were included. Most of the cases were premenopausal 17 (74.0%). Synchronous coexistence occurred in 15 (65.2%), with ipsilateral involvement in 11 (73.3%) of these. Granulomatous mastitis preceded BC in 6 (26.1%) (median interval 3 years), and BC preceded GM in 2 (8.7%). Core needle biopsy diagnosed GM in 9 (39.1%) and BC in 14 (60.9%); excisional biopsy was required in 7 (30.4%) of GM cases. Breast cancer treatment included mastectomy in 11 (47.8%) and breast-conserving surgery in 9 (39.1%). Follow-up ranged from 2–53 months. Conclusion: Granulomatous mastitis and BC can coexist, with GM potentially masking malignancy. Clinicians should maintain a low threshold for repeat biopsy in refractory cases. Introduction Granulomatous mastitis (GM) is a rare, chronic inflammatory breast disease, first described in 1972 as a lesion mimicking carcinoma [1,2]. It is characterized by non-caseating granulomatous inflammation centered on breast lobules, typically affecting women of childbearing age, often within five years of their last childbirth [3,4]. The incidence of idiopathic GM is estimated at 2.4 per 100,000 women aged 20-40 years, with higher rates among Asian, Hispanic, and Arab populations [5]. Although the exact etiology remains unclear, proposed mechanisms include autoimmune processes, hormonal imbalances, oral contraceptive use, hyperprolactinemia, pregnancy and lactation, alpha-1 antitrypsin deficiency, and infectious agents [6,7]. While GM is generally benign, several reports have documented its occurrence alongside breast carcinoma. The coexistence of GM and breast cancer (BC) presents a rare but clinically significant diagnostic and therapeutic challenge [7]. The literature contains case reports and small series of patients with concurrent or metachronous GM and BC, encompassing invasive ductal carcinoma (IDC), ductal carcinoma in situ (DCIS), and lobular carcinoma in situ (LCIS) [8,9]. The pathophysiological relationship between GM and BC is not fully understood. Two main hypotheses have been proposed. First, the granulomatous response may represent a secondary "sarcoid-like reaction" to breast carcinoma first described in 1911, reflecting immunological hypersensitivity to tumor-derived antigens [7,10]. Second, chronic inflammation from GM may predispose to dysplasia and subsequent malignant transformation [7,10]. This systematic review aims to examine the coexistence of GM and breast carcinoma, focusing on the clinicopathological features of synchronous and metachronous cases. Methods Study design This review followed Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines [11]. Information sources and search strategy A systematic literature search was conducted in PubMed/MEDLINE and Google Scholar for published studies up to 30th of November 2025. The following medical keywords and search terms were used for Google Scholar: (cancer OR cancers OR cancerous OR carcinoma OR carcinomas OR neoplasm OR neoplasms OR malignancy OR malignancies OR malignant OR metastasis OR tumor OR tumors) AND ("granulomatous mastitis" OR GM). And these keywords were used in PubMed/MEDLINE: ("granulomatous mastitis"[tiab] OR GM [tiab] OR "Granulomatous Mastitis"[Mesh]) AND (cancer[tiab] OR cancers[tiab] OR carcinoma[tiab] OR carcinomas[tiab] OR neoplasm[tiab] OR neoplasms[tiab] OR malignancy[tiab] OR malignancies[tiab] OR malignant[tiab] OR metastasis[tiab] OR tumor[tiab] OR tumors[tiab] OR "Breast Neoplasms"[Mesh]). Inclusion Criteria Studies were included if they met the following criteria: 1) Studies reporting individual patient-level data, 2) patients diagnosed with both GM and BC, either concurrently or sequentially, 3) the diagnosis of both BC and GM was confirmed by diagnostic imaging, surgical findings, or histopathological examination. All included studies underwent eligibility verification [12]. Exclusion Criteria Exclusion criteria included all of the following: 1) Studies with no human subjects, 2) studies that were published in the form of conference abstracts, 3) studies published in non-recommended journals, and 4) non-English papers. Data extraction The extracted data included the following variables: The first author's name, year of publication, and country of study. Patient demographic and reproductive characteristics included age, parity, menopausal status, lactation history, oral contraceptive use, and smoking status. Clinical presentation data included the chief complaint, duration of symptoms before diagnosis, side and quadrant of the affected breast, and family history of BC. Regarding the relationship between GM and BC, the laterality of each pathology and the chronological sequence of the two diagnoses were recorded. Diagnostic data included the sampling and diagnosis method, type of GM, and imaging findings on mammography, ultrasound, and magnetic resonance imaging (MRI), along with the assigned Breast Imaging-Reporting and Data System (BI-RADS) category. Breast cancer-specific variables comprised the type and grade of cancer, hormone receptor status such as estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), cancer stage, and metastasis status. Finally, management data included the treatment approaches applied for both GM and BC, and the follow-up duration. Granulomatous Mastitis and BC were classified as synchronous when both were diagnosed concurrently or within 6 months of one another, and as metachronous when the interval between the two diagnoses exceeded 6 months [13]. Statistical Analysis Descriptive statistics were used to summarize categorical variables as frequencies and percentages. Continuous variables (e.g., age, follow-up duration) were summarized as means with ranges or medians with ranges, as appropriate. All analyses were conducted using Microsoft Excel (version 16.0). Results Study selection A total of 236 records were identified from PubMed/MEDLINE and Google Scholar. After removing 42 duplicates, 194 records were screened. Of these, 173 were excluded based on title and abstract review, leaving 21 reports to be sought for retrieval, all of which were successfully retrieved. Following eligibility assessment, 2 reports were excluded (one as it was a historical report predating the formal definition of GM, and the other one due to publication in a non-recommended journal). Ultimately, 19 studies were included in the final review (Figure 1). Characteristics of the included studies A comprehensive literature search yielded a total of 23 eligible cases from 19 published reports [2,4-10,14-24] documenting the coexistence of GM and BC. These cases were derived from case reports and case series published between 2012 and 2025. The included cases originated from multiple countries; most commonly from Iran (7, 30.4%) and China (5, 21.7%), followed by Iraq and Turkey (2, 8.7%), with single cases reported from Brazil, Chile, Japan, Australia, Malaysia, Tunisia, and Pakistan (Tables 1 & 2). Table 1. Demographic and clinical characteristics of patients with coexisting granulomatous mastitis and breast cancer Author (year) [ref] N Country Age (years) Presentation Duration of Symptoms Parity Menopausal Lactation OCP Smoking FH of BC Salih et al., 2025 [2] 1 Iraq 36 Breast pain 2w 3 Pre 4y, currently nursing No Passive No Freitas et al., 2020 [20] 1 Brazil 42 Breast nodule enlargement NA 2 Pre 5y No NA No Zavieh et al., 2024 [8] 3 Iran 42 Breast Pain and lump NA 2 Pre 48m, 20y ago Yes NA No 46 Mass NA 2 Pre 9y before GM No NA No 41 Mass NA NA Pre NA No NA No Zhu et al., 2024 [18] 3 China 51 Hard mass 1d NA Post NA NA NA NA 50 Recurrent mass NA NA Peri NA NA NA NA 45 Lump with redness, heat, pain, nipple retraction and discharge 2m NA Peri NA NA NA NA Oddó et al., 2019 [6] 1 Chile 44 Pain and swelling 2w NA NA NA NA Former No Tavakol et al., 2022 [9] 1 Iran 35 Pain & mass 1m 2 Pre NA No NA No Yoshida et al., 2023 [4] 1 Japan 34 Mass & redness NA NA Pre NA NA NA No Zangouri et al., 2022 [22] 1 Iran 38 Mass NA NA Pre 28m NA NA NA Çalış and Kilitçi, 2018 [19] 1 Turkey 77 Pain & swelling NA NA Post NA NA NA NA Xie et al., 2022 [23] 1 China 39 Enlarging mass, pain, redness NA 1 Pre NA NA NA No Evans et al., 2021 [17] 1 Australia 39 Mass increasing in size & tenderness NA 2 Pre NA NA NA No Salih et al., 2023 [16] 1 Iraq 30 Pain 7d 3 Pre 6m, 3y ago No No Yes Mazlan et al., 2012 [24] 1 Malaysia 34 Progressive loss of vision in the left eye NA NA