Mucoepidermoid Carcinoma of the Breast: A Systematic Review of Clinicopathologic, Immunohistochemical, and Molecular Features

Background: Mucoepidermoid carcinoma (MEC) of the breast is a very rare salivary gland-like tumor, accounting for 0.2%–0.3% of all breast cancers (BC). This study aims to review the literature on MEC of the breast. Methods: This systematic review focuses on MEC of the breast, conducted in line with PRISMA 2020 guidelines and registered in PROSPERO under ID CRD420251089598. Searches were performed in PubMed, Medline, Scopus, Web of Science, and Google Scholar, using terms such as “mucoepidermoid carcinoma,” “breast,” and similar terms. No language restrictions were applied. Studies published between January 1, 1979, and July 1, 2025, were included. Results: Median age was 57 years (95% CI: 53–60). The most common presentation was a palpable breast mass (64.7%), followed by incidental detection via mammography (10.6%). Tumors were located in the left breast (49.4%) and in the right breast (43.5%). The most frequent tumor localization was the upper-outer quadrant (20.0%). Median tumor size was 21 mm (95% CI: 19–30). Modified radical mastectomy (30.6%) was the most common surgical approach, followed by breast-conserving surgery with sentinel or level dissection (29.4%), and simple mastectomy or its variants (17.6%). Immunohistochemistry revealed positivity for P63 (52.9%), CK5/6 (41.2%), CK7 (45.9%), Ki67 (44.7%), ER (24.7%), PR (4.7%), and HER2 (9.4%) with TNBC phenotype (36.5%), genetic alterations (16.5%), and distant metastasis (9.4%). Follow-up data revealed 7 deaths, of which 5 were due to MEC, and these five patients consistently exhibited poor prognostic features. Compared to the 63 survivors with follow-up data, they showed significantly higher rates of axillary lymph node positivity (p = 0.005) and advanced N stage (p = 0.001); in addition, all five had high-grade tumors (p = 0.001) and documented distant metastases (p < 0.001). Conclusion: Breast MEC is a rare malignancy with generally favorable prognosis in low-grade cases, but high-grade tumors show more aggressive behavior. In this study, all disease-related deaths occurred in high-grade tumors with axillary node involvement, advanced N stage, and distant metastasis—highlighting their prognostic significance. CK5/6, CK7, and P63 were frequently positive, whereas hormone receptors were usually negative. Close follow-up is essential, especially for high-grade tumors. Review Registration: This systematic review was prospectively registered in the PROSPERO database under the registration number CRD420251089598.