Metaplastic carcinoma (MPC), an uncommon but often aggressive breast cancer, can be challenging to differentiate from other types of breast cancer and even benign lesions based on the imaging appearance. It has a variable pathology classification system. These types of tumors are generally rapidly growing palpable masses. MPCs on imaging can present with imaging features similar to invasive ductal carcinoma and probably even benign lesions. The purpose of this article is to review MPC of the breast including the pathology subtypes, imaging features, and imaging pathology correlations. By understanding the clinical picture, pathology, and overlap in imaging characteristics of MPC with invasive ductal carcinoma and probably benign lesions can assist in diagnosing these difficult malignancies.

Mammographers occasionally are surprised by the diagnosis of a rare lesion at breast biopsy. The imaging features of some breast lesions are unfamiliar because they are rarely seen in routine mammographic practice and they are not well described or well documented in the radiologic literature. Moreover, there may be wide variation in the appearances of rare breast lesions at mammography and ultrasonography (US). In addition, although a few rare breast lesions have a typical imaging appearance, most have mammographic and US features similar to those of breast carcinomas, and a needle biopsy is almost always necessary to obtain a diagnosis. However, even when a rare breast lesion is diagnosed on the basis of a needle biopsy, knowledge of the imaging features of such lesions may help the radiologist decide whether the results of pathologic analysis concur with the imaging findings and whether surgical excision is necessary. It is therefore important that radiologists be familiar with the broad spectrum of imaging features of rare breast lesions as well as with the correlation between their histopathologic features and their current classification according to the World Health Organization classification system.

NOV-002 (a formulation of disodium glutathione disulfide) modulates signaling pathways involved in tumor cell proliferation and metastasis and enhances anti-tumor immune responsiveness in tumor models. The addition of NOV-002 to chemotherapy has been shown to increase anti-tumor efficacy in animal models and some early phase oncology trials. We evaluated the clinical effects of NOV-002 in primary breast cancer, whether adding NOV-002 to standard preoperative chemotherapy increased pathologic complete response rates (pCR) at surgery, and determined whether NOV-002 mitigated hematologic toxicities of chemotherapy and whether levels of myeloid derived suppressor cells (MDSC) were predictive of response. Forty-one women with newly diagnosed stages II-IIIc HER-2 negative breast cancer received doxorubicin-cyclophosphamide followed by docetaxel (AC→T) every 3 weeks and concurrent daily NOV-002 injections. The trial was powered to detect a doubling of pCR rate from 16% to 32% with NOV-002 plus AC→T (α=0.05, β=80%). Weekly complete blood counts were obtained as well as circulating MDSC levels on day 1 of each cycle were quantified. Of 39 patients with 40 evaluable tumors, 16 achieved a pCR (40%), meeting the primary endpoint of the trial. Lower circulating levels of MDSCs at baseline and cycle 8 were associated with a pCR (P=0.02). Concurrent NOV-002 resulted in pCR rates for AC→T chemotherapy higher than previously reported. Patients with lower levels of circulating MDSCs at baseline and on the last cycle of chemotherapy had significantly higher probability of a pCR (p=0.02). Further evaluation of NOV-002 in a randomized study is warranted.

ETS factors have been shown to be dysregulated in breast cancer. ETS factors control the expression of genes involved in many biological processes, such as cellular proliferation, differentiation, and apoptosis. FLI1 is an ETS protein aberrantly expressed in retrovirus-induced hematological tumors, but limited attention has been directed towards elucidating the role of FLI1 in epithelial-derived cancers. Using data mining, we show that loss of FLI1 expression is associated with shorter survival and more aggressive phenotypes of breast cancer. Gain and loss of function cellular studies indicate the inhibitory effect of FLI1 expression on cellular growth, migration, and invasion. Using Fli1 mutant mice and both a transgenic murine breast cancer model and an orthotopic injection of syngeneic tumor cells indicates that reduced Fli1 contributes to accelerated tumor growth. Global expression analysis and RNA-Seq data from an invasive human breast cancer cell line with over expression of either FLI1 and another ETS gene, PDEF, shows changes in several cellular pathways associated with cancer, such as the cytokine-cytokine receptor interaction and PI3K-Akt signaling pathways. This study demonstrates a novel role for FLI1 in epithelial cells. In addition, these results reveal that FLI1 down-regulation in breast cancer may promote tumor progression.