N-Myc Interactor is an inducible protein whose expression is compromised in advanced stage breast cancer. Downregulation of NMI, a gatekeeper of epithelial phenotype, in breast tumors promotes mesenchymal, invasive and metastatic phenotype of the cancer cells. Thus the mechanisms that regulate expression of NMI are of potential interest for understanding the etiology of breast tumor progression and metastasis. Web based prediction algorithms were used to identify miRNAs that potentially target the NMI transcript. Luciferase reporter assays and western blot analysis were used to confirm the ability of miR-29 to target NMI. Quantitive-RT-PCRs were used to examine levels of miR29 and NMI from cell line and patient specimen derived RNA. The functional impact of miR-29 on EMT phenotype was evaluated using transwell migration as well as monitoring 3D matrigel growth morphology. Anti-miRs were used to examine effects of reducing miR-29 levels from cells. Western blots were used to examine changes in GSK3β phosphorylation status. The impact on molecular attributes of EMT was evaluated using immunocytochemistry, qRT-PCRs as well as Western blot analyses. Invasive, mesenchymal-like breast cancer cell lines showed increased levels of miR-29. Introduction of miR-29 into breast cancer cells (with robust level of NMI) resulted in decreased NMI expression and increased invasion, whereas treatment of cells with high miR-29 and low NMI levels with miR-29 antagonists increased NMI expression and decreased invasion. Assessment of 2D and 3D growth morphologies revealed an EMT promoting effect of miR-29. Analysis of mRNA of NMI and miR-29 from patient derived breast cancer tumors showed a strong, inverse relationship between the expression of NMI and the miR-29. Our studies also revealed that in the absence of NMI, miR-29 expression is upregulated due to unrestricted Wnt/β-catenin signaling resulting from inactivation of GSK3β. Aberrant miR-29 expression may account for reduced NMI expression in breast tumors and mesenchymal phenotype of cancer cells that promotes invasive growth. Reduction in NMI levels has a feed-forward impact on miR-29 levels.

Breast cancer is a significant health challenge worldwide and is the most frequently diagnosed cancer among women globally. This review provides a comprehensive overview of breast cancer biology, genomics, and microbial dysbiosis, focusing on its various subtypes and racial differences. Breast cancer is primarily classified into carcinomas and sarcomas, with carcinomas constituting most cases. Epidemiology and breast cancer risk factors are important for public health intervention. Staging and grading, based on the TNM and Nottingham grading systems, respectively, are crucial to determining the clinical outcome and treatment decisions. Histopathological subtypes include in situ and invasive carcinomas, such as invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC). The review explores molecular subtypes, including Luminal A, Luminal B, Basal-like (Triple Negative), and HER2-enriched, and delves into breast cancer’s histological and molecular progression patterns. Recent research findings related to nuclear and mitochondrial genetic alterations, epigenetic reprogramming, and the role of microbiome dysbiosis in breast cancer and racial differences are also reported. The review also provides an update on breast cancer’s current diagnostics and treatment modalities.

Primary breast sarcomas are uncommon and primary mammary malignant peripheral nerve sheet tumors (MPNST) are exceptionally rare. MPNSTs are malignant variants of peripheral nerve sheath tumors. These neoplasms are often associated with neurofibromatosis type I (NF-I) but can also occur sporadically. They tend to occur in the deeper soft tissues, trunk, and extremities. A 60-year-old Asian female was referred to our surgical clinic for evaluation of a left breast mass and an abnormal mammogram. The patient noticed the mass in the left breast three months earlier and was referred for mammography by her primary physician. Mammography reported partially defined masses in the superior aspect of the left breast, and ultrasound showed a solid mass measuring 5.2 X 3 cm. The mass was 11 cm on clinical exam. Subsequent core biopsy of the left breast lesion showed high-grade malignant neoplasm. Workup showed no evidence of metastatic disease, and the patient underwent modified radical mastectomy. The neoplastic cells were positive for CD99, S-100, SOX-10, neuron specific enolase, p53, vimentin, focally positive for neurofilament, D2-40, p63, and negative for epithelial, melanoma and other sarcoma markers. The tumor was triple negative estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), with Ki-67 at 61%. A diagnosis of primary high grade malignant peripheral nerve sheath tumor of the breast was rendered. The patient does not have a history of NF-1. An accurate diagnosis of this rare entity is necessary because it plays a crucial role in the therapeutic options and prognosis. In our case the patient underwent modified radical mastectomy. The purpose of presenting this unique case is to provide awareness of the existence of this entity among pathologists and clinicians for better patient care.