Invasive lobular carcinoma (ILC) and lobular neoplasia (LN) are two distinct conditions that still pose challenges regarding to their classification, diagnosis and management. Although they share similar cellular characteristics, such as discohesive neoplastic cells and absence of e-cadherin staining, they represent completely different conditions. LN encompasses atypical lobular hyperplasia (ALH) and lobular carcinoma in situ (LCIS), which are currently considered risk factors and non-obligatory precursors of breast neoplasia. These lesions are diagnosed as incidental findings in percutaneous biopsies or appear as non-specific clusters of punctate calcifications in mammograms. ILC is the second most common breast malignancy and has typical histological features, such as infiltrative growth and low desmoplasia. These histological features are reflected in imaging findings and constitute the reasons for typical subtle mammographic features of ILC, as architectural distortion or focal asymmetries. Ultrasonography (US) may detect almost 75 % of the ILCs missed by mammography and represents the modality of choice for guiding biopsies. Magnetic resonance imaging (MRI) exhibits a high sensitivity for the diagnosis of ILC and for detecting synchronous lesions.Teaching Points• LN includes ALH and LCIS, risk factors and non-obligatory precursors of breast cancer.• Absence of e-cadherin staining is crucial for differentiation among ductal and lobular lesions.• ILC has typical histological features, such as infiltrative growth and low desmoplasia.• Mammographic features of ILC are often subtle and reflect the histological features.• MRI exhibits a high sensitivity for the diagnosis of ILC and for detecting synchronous lesions.
Breast cancer is the most common cancer in women worldwide and metastatic dissemination is the principal factor related to death by this disease. Breast cancer stem cells (bCSC) are thought to be responsible for metastasis and chemoresistance. In this study, based on whole transcriptome analysis from putative bCSC and reverse engineering of transcription control networks, we identified two networks associated with this phenotype. One controlled by SNAI2, TWIST1, BNC2, PRRX1 and TBX5 drives a mesenchymal or CSC-like phenotype. The second network is controlled by the SCML4, ZNF831, SP140 and IKZF3 transcription factors which correspond to immune response modulators. Immune response network expression is correlated with pathological response to chemotherapy, and in the Basal subtype is related to better recurrence-free survival. In patient-derived xenografts, the expression of these networks in patient tumours is predictive of engraftment success. Our findings point out a potential molecular mechanism underlying the balance between immune surveillance and EMT activation in breast cancer. This molecular mechanism may be useful to the development of new target therapies.
PURPOSE:To evaluate the outcomes and diagnostic performance of ultrasonography after a Breast Imaging Reporting and Data System (Bi-RADS) category 0 mammogram.MATERIAL AND METHODS:This retrospective study reviewed 4,384 consecutive patients who underwent a screening mammography from January 2005 to July 2006; 391 of the 4,384 exams were classified as Bi-RADS category 0. After exclusions, 241 patients received subsequent sonogram. Ultrasonography was considered diagnostic when the Bi-RADS category was changed to 2, 4, or 5, and it was considered indeterminate (Bi-RADS 3) when the results indicated that the patients should return for a mammographic follow-up. The outcomes of these patients were assessed to evaluate the diagnostic performance of ultrasonography.RESULTS:The mean age of the patients was 53.3 years (ranging from 35 to 81). Of the 241 patients, ultrasonography was considered diagnostic in 146 (60.6%) patients and indeterminate in 95 (39.4%) patients. In the diagnostic group, 111 out of 146 patients (70.2%) had a sonogram result of Bi-RADS category 2 after a 2-year follow-up without evidence of malignancy. Furthermore, 35 out of 146 patients (29.8%) had a suspicious sonogram with a result of Bi-RADS category 4. After a tissue sampling procedure, 10 patients were confirmed to have breast cancer, and 25 had benign histopathological features without any evidence of malignancy after a 2-year follow-up. The sensitivity of ultrasonography was 100%, specificity was 89.1%, and overall accuracy was 89.6%.CONCLUSIONS:Based on the degree of resolution and its diagnostic performance, ultrasonography was determined to be an excellent method for the subsequent evaluation of Bi-RADS 0 mammograms.
The existence of tumor-initiating cells (TICs) within solid tumors has been hypothesized to explain tumor heterogeneity and resistance to cancer therapy. In breast cancer, the expression of CD44 and CD24 and the activity of aldehyde dehydrogenase 1 (ALDH1) can be used to selectively isolate a cell population enriched in TICs. However, the ideal marker to identify TICs has not been established. The aim of this study was to evaluate the expression of novel potential markers for TIC in breast carcinoma. We prospectively analyzed the expression of CD44, CD24, ABCG2, and CXCR4, and the activity of ALDH1 by using flow cytometry in 48 invasive ductal carcinomas from locally advanced and metastatic breast cancer patients who were administered primary chemotherapy. A mammosphere assay was employed in 30 samples. The relationship among flow cytometric analyses, ABCG2 gene expression, and clinical and pathological responses to therapy was analyzed. The GSE32646 database was analyzed in silico to identify genes associated with tumors with low and high ABCG2 expression. We observed that the presence of ABCG2(+) cells within the primary tumor was the only marker to predict the formation of mammospheres in vitro (R (2) = 0.15, p = 0.029). Quantitative polymerase chain reaction (qPCR) revealed a positive correlation between ABCG2 expression and the presence of ABCG2(+) cells within the primary tumor. The expression of ABCG2 was predictive of the response to neoadjuvant chemotherapy in our experiments and in the GSE32646 dataset (p = 0.04 and p = 0.002, respectively). The in silico analysis demonstrated that ABCG2(Up) breast cancer samples have a slower cell cycle and a higher expression of membrane proteins but a greater potential for chromosomal instability, metastasis, immune evasion, and resistance to hypoxia. Such genetic characteristics are compatible with highly aggressive and resistant tumors. Our results support the hypothesis that the presence of ABCG2(+) cells in breast carcinomas is a marker of resistance to chemotherapy, and based on in vitro assays and the genetic profile, we show, for the first time, that ABCG2 protein can be used as an independent marker for TIC identification in breast cancer.
The present essay is aimed at describing the most characteristic imaging findings of mucinous carcinoma of the breast, with emphasis on the patterns related to better prognosis. The authors selected cases of mucinous carcinoma of the breast whose images were available, highlighting the imaging findings suggestive of this subtype of breast cancer, either at mammography, ultrasonography or magnetic resonance imaging.
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