MicroRNA signatures differentiate types, grades, and stages of breast invasive ductal carcinoma (IDC): miRNA-target interacting signaling pathways.

BACKGROUND: Invasive ductal carcinoma (IDC) is the most common form of breast cancer which accounts for 85% of all breast cancer diagnoses. Non-invasive and early stages have a better prognosis than late-stage invasive cancer that has spread to lymph nodes. The involvement of microRNAs (miRNAs) in the initiation and progression of breast cancer holds great promise for the development of molecular tools for early diagnosis and prognosis. Therefore, developing a cost effective, quick and robust early detection protocol using miRNAs for breast cancer diagnosis is an imminent need that could strengthen the health care system to tackle this disease around the world. METHODS: We have analyzed putative miRNAs signatures in 100 breast cancer samples using two independent high fidelity array systems. Unique and common miRNA signatures from both array systems were validated using stringent double-blind individual TaqMan assays and their expression pattern was confirmed with tissue microarrays and northern analysis. In silico analysis were carried out to find miRNA targets and were validated with q-PCR and immunoblotting. In addition, functional validation using antibody arrays was also carried out to confirm the oncotargets and their networking in different pathways. Similar profiling was carried out in Brca2/p53 double knock out mice models using rodent miRNA microarrays that revealed common signatures with human arrays which could be used for future in vivo functional validation. RESULTS: Expression profile revealed 85% downregulated and 15% upregulated microRNAs in the patient samples of IDC. Among them, 439 miRNAs were associated with breast cancer, out of which 107 miRNAs qualified to be potential biomarkers for the stratification of different types, grades and stages of IDC after stringent validation. Functional validation of their putative targets revealed extensive miRNA network in different oncogenic pathways thus contributing to epithelial-mesenchymal transition (EMT) and cellular plasticity. CONCLUSION: This study revealed potential biomarkers for the robust classification as well as rapid, cost effective and early detection of IDC of breast cancer. It not only confirmed the role of these miRNAs in cancer development but also revealed the oncogenic pathways involved in different progressive grades and stages thus suggesting a role in EMT and cellular plasticity during breast tumorigenesis per se and IDC in particular. Thus, our findings have provided newer insights into the miRNA signatures for the classification and early detection of IDC.

Prediction of coexisting invasive carcinoma on ductal carcinoma in situ (DCIS) lesions by mass spectrometry imaging.

Due to limited biopsy samples, ~20% of DCIS lesions confirmed by biopsy are upgraded to invasive ductal carcinoma (IDC) upon surgical resection. Avoiding underestimation of IDC when diagnosing DCIS has become an urgent challenge in an era discouraging overtreatment of DCIS. In this study, the metabolic profiles of 284 fresh frozen breast samples, including tumor tissues and adjacent benign tissues (ABTs) and distant surrounding tissues (DSTs), were analyzed using desorption electrospray ionization-mass spectrometry (DESI-MS) imaging. Metabolomics analysis using DESI-MS data revealed significant differences in metabolite levels, including small-molecule antioxidants, long-chain polyunsaturated fatty acids (PUFAs) and phospholipids between pure DCIS and IDC. However, the metabolic profile in DCIS with invasive carcinoma components clearly shifts to be closer to adjacent IDC components. For instance, DCIS with invasive carcinoma components showed lower levels of antioxidants and higher levels of free fatty acids compared to pure DCIS. Furthermore, the accumulation of long-chain PUFAs and the phosphatidylinositols (PIs) containing PUFA residues may also be associated with the progression of DCIS. These distinctive metabolic characteristics may offer valuable indications for investigating the malignant potential of DCIS. By combining DESI-MS data with machine learning (ML) methods, various breast lesions were discriminated. Importantly, the pure DCIS components were successfully distinguished from the DCIS components in samples with invasion in postoperative specimens by a Lasso prediction model, achieving an AUC value of 0.851. In addition, pixel-level prediction based on DESI-MS data enabled automatic visualization of tissue properties across whole tissue sections. Summarily, DESI-MS imaging on histopathological sections can provide abundant metabolic information about breast lesions. By analyzing the spatial metabolic characteristics in tissue sections, this technology has the potential to facilitate accurate diagnosis and individualized treatment of DCIS by inferring the presence of IDC components surrounding DCIS lesions. © 2023 The Pathological Society of Great Britain and Ireland.

Synchronous double primary small cell lung cancer and invasive ductal breast carcinoma: a case report.

BACKGROUND: Although lung and breast cancers are common malignancies, the occurrence of primary synchronous neoplasms involving these organs has been rarely reported in literature. CASE PRESENTATION: A 75-year-old female patient presented at a local hospital with a ten-day history of dizziness and slurred speech. A CT contrast-enhanced scan revealed a 4.2 cm mass in the lower lobe of the right lung and a 3.8 cm space-occupying lesion in the right breast. Subsequent breast ultrasound identified a hypoechoic lesion measuring5.41 × 4.75 × 3.06 cm in the right breast, and an ultrasound-guided biopsy confirmed the presence of infiltrating ductal carcinoma of the right breast. The immunohistochemistry analysis of the breast mass revealed positive staining for ER, PR, HER-2, AR and Ki67 in the tumor cells, while negative staining was observed for P63, Calponin, CK5/6 and CK14. MR imaging of the head detected abnormal signals in the right frontal lobe (3.6 cm×2.9 cm in size), left cerebellar hemisphere, and punctate enhancement in the left temporal lobe, indicating potential metastasis. Pathological examination of a lung biopsy specimen confirmed the presence of small cell lung cancer (SCLC). Furthermore, immunohistochemistry analysis of the lung lesions demonstrated positive staining for TTF-1, CK-Pan, Syn, CgA, CD56, P53 (90%) and Ki67 (70%), and negative staining for NapsinA and P40 in the tumor cells. The patient's diagnosis of SCLC with stage cT2bN0M1c IVB and brain metastases (BM), as well as invasive ductal breast carcinoma (IDC), was confirmed based on the aforementioned results. Whereupon we proposed a treatment plan consisting of whole-brain radiation (40 Gy/20fractions), focal radiotherapy (60 Gy/20fractions), and adjuvant concurrent chemotherapy with oral etoposide (50 mg on days 1 to 20). CONCLUSIONS: To the best of our knowledge, the present case is the first of its kind to describe the synchronous double cancer, consisting of primary SCLC and IDC.

Application Value of Ultrasound Elastography Combined With Contrast-Enhanced Ultrasound (CEUS) Quantitative Analysis in Differentiation of Nodular Fibrocystic Changes of the Breast From Invasive Ductal Carcinoma.

This study aimed to compare the value of ultrasound elastography combined with contrast-enhanced ultrasound (CEUS) quantitative analysis in the differentiation of nodular fibrocystic breast change (FBC) from breast invasive ductal carcinoma (BIDC). We selected 50 patients each with nodular FBC and BIDC, who were admitted to the Affiliated Hospital of Zunyi Medical University from January 2018 to December 2021. Their ultrasonic elastic images and CEUS videos were collected, their ultrasound elastography scores and the ratio of strain rate (SR) of the lesions were determined, and the exported DICOM format videos of CEUS were quantitatively analyzed using VueBox software to obtain quantitative perfusion parameters. The differences between the ultrasound elastography score and SR while comparing nodular FBC and BIDC cases were statistically significant (p < .05). The sensitivity, specificity, and accuracy of ultrasound elastography scores in the differential diagnoses of nodular FBC and BIDC were 74%, 88%, and 81%, respectively. Additionally, the sensitivity, specificity, and accuracy of SR in the differential diagnosis of nodular FBC and BIDC were 94%, 78%, and 86%, respectively. Statistically significant differences were observed in the CEUS quantitative perfusion parameters PE, AUC (WiAUC, WoAUC, WiWoAUC), and WiPI in both nodular FBC and BIDC according to the VueBox software (p < .05). The sensitivity, specificity, and accuracy of CEUS quantitative analysis in the differential diagnoses of nodular FBC and BIDC were 66%, 82%, and 74%, respectively. Using the pathological findings as the gold standard, ROC curves were established, and the area under the curve (AUC) of the CEUS quantitative analysis, elasticity score, SR, and ultrasound elastography combined with CEUS quantitative analysis were 0.731, 0.838, and 0.892, as well as 0.945, respectively. Ultrasound elasticity scoring, SR and CEUS quantitative analysis have certain application value for differentiating nodular FBC cases from BIDC; however, ultrasound elasticity imaging combined with CEUS quantitative analysis can help in improving the differential diagnostic efficacy of nodular FBC cases from BIDC.

Ultrasound characteristics of breast fibromatosis mimicking carcinoma.

PURPOSE: To explore the value of ultrasound (US) characteristics in diagnosing breast fibromatosis (BF) and evaluate their differences from breast carcinoma. METHODS: A total of 121 patients with BF (n = 24, 29 lesions) or invasive ductal carcinoma (IDC) (n = 97, 102 lesions) of the breast were included. Their clinical and US findings were recorded and analyzed. RESULTS: The mean age of BF was younger than that of IDC (28.75 ± 5.55 vs. 50.19 ± 9.87, p < 0.001). The mean size of the BF was smaller than that of IDC (2.09 ± 0.91 vs. 2.71 ± 1.20, p = 0.011). Compared to IDC, BF had more frequency of posterior echo attenuation (p < 0.001), less frequency of peripheral hyperechoic halo (p = 0.002), calcification (p = 0.001), US reported axillary lymph node positive (p = 0.025), and grade 2-3 vascularity (p < 0.001). The Breast Imaging Reporting and Data System categorized BF at a lower level than IDC (p < 0.001). After adjusting for age, the peripheral hyperechoic halo, posterior echo feature, and vascularity could independently identify the differences between these two entities. CONCLUSION: Some differences were observed between BF and IDC in terms of patient age, lesion size, and US characteristics.

Extracellular Microenvironment Alterations in Ductal Carcinoma In Situ and Invasive Breast Cancer Pathologies by Multiplexed Spatial Proteomics.

Ductal carcinoma in situ (DCIS) is a heterogeneous breast disease that remains challenging to treat due to its unpredictable progression to invasive breast cancer (IBC). Contemporary literature has become increasingly focused on extracellular matrix (ECM) alterations with breast cancer progression. However, the spatial regulation of the ECM proteome in DCIS has yet to be investigated in relation to IBC. We hypothesized that DCIS and IBC present distinct ECM proteomes that could discriminate between these pathologies. Tissue sections of pure DCIS, mixed DCIS-IBC, or pure IBC (n = 22) with detailed pathological annotations were investigated by multiplexed spatial proteomics. Across tissues, 1,005 ECM peptides were detected in pathologically annotated regions and their surrounding extracellular microenvironments. A comparison of DCIS to IBC pathologies demonstrated 43 significantly altered ECM peptides. Notably, eight fibrillar collagen peptides could distinguish with high specificity and sensitivity between DCIS and IBC. Lesion-targeted proteomic imaging revealed heterogeneity of the ECM proteome surrounding individual DCIS lesions. Multiplexed spatial proteomics reported an invasive cancer field effect, in which DCIS lesions in closer proximity to IBC shared a more similar ECM profile to IBC than distal counterparts. Defining the ECM proteomic microenvironment provides novel molecular insights relating to DCIS and IBC.

Gastric Metastasis Mimicking Early Gastric Cancer from Invasive Ductal Carcinoma of the Breast: Case Report and Literature Review.

Backgound and Objectives: Gastric metastasis from invasive ductal breast cancer (BC) is rare. It mainly occurs in patients with lobular BC. The occurrence of multiple metastases is typically observed several years after the primary diagnosis. Endoscopic findings of gastric metastasis of the BC were usually the linitis plastic type. Case presentation: A 72-year-old women who underwent right modified radical mastectomy (MRM) 10 month ago was referred after being diagnosed with early gastric cancer (EGC) during systemic chemotherapy. EGC type I was found at gastric fundus, and pathologic finding showed poorly differentiated adenocarcinoma. Metachronous double primary tumor EGC was considered. Management and Outcome: A laparoscopic total gastrectomy was performed, and postoperative pathology revealed submucosa invasion and two lymph node metastases. A pathologic review that focused on immunohistochemical studies of selected antibodies such as GATA binding protein 3 (GATA3), gross cystic disease fluid protein-15 (GCDFP-15), cytokeratin 7 (CK7) was performed again, comparing previous results. As a result, gastric metastasis from BC was diagnosed. After totally laparoscopic total gastrectomy, palliative first-line chemotherapy with paclitaxel/CDDP was performed. Two months after gastrectomy, she was diagnosed with para-aortic lymph node metastasis and multiple bone metastases. She expired six months after gastrectomy. Conclusions: Gastric metastasis from invasive ductal carcinoma of the breast, which is clinically manifested as EGC, is a very rare condition. If there is a history of BC, careful pathological review will be required.

Clinical characteristics and treatment outcomes of invasive ductal and lobular carcinoma: analyses of 54,832 taiwan cancer registry index cases.

PURPOSE: Invasive lobular cancer (ILC) is the second most common histology type of breast cancer followed by invasive ductal carcinoma (IDC). This study aimed to investigate the characteristic, treatment strategies, and clinical outcomes of ILC based on a national population-based cancer registry. METHODS: This study recruited 2671 ILC and 52,215 IDC patients diagnosed between 2011 and 2017 using the Taiwan Cancer Registry (TCR). Correlations between ILC and IDC subgroups were assessed using 1:4 propensity score matching and compared using the χ2 test. Disease free survival(DFS) and overall survival(OS) were estimated using the Kaplan-Meier method with the log-rank test. The risk of disease relapse and mortality were assessed using Cox proportional hazards model. RESULTS: ILC patients had larger tumor sizes, more positive axillary lymph node involvement, lower tumor grade, and higher cancer stage than IDC patients. After matching, ILC patients had a significantly higher rate of receiving mastectomy (58.93% and 53.85%) and positive surgical margin regardless of surgery type. ILC exhibited a significantly higher rate of distant metastasis than IDC(3.67% and 2.93%), but no difference in local recurrence rate, DFS or OS between the two groups. Higher cancer stage, higher grade, and mastectomy were risk factors for disease relapse and cancer-specific mortality. The hormone receptor-positive and HER2 over-expression subtypes were found to be associated with a reduced risk of disease relapse, while only PR positivity was associated with a decreased risk of mortality. (all P-values < 0.05). CONCLUSION: ILC patients had a higher mastectomy rate, higher surgical margin rate and distant metastasis rate than IDC patients. There is no significant difference in DFS or OS between ILC and IDC patients. Mastectomy was associated with poor outcomes regardless of ILC or IDC.

Bioinformatics analyses of combined databases identify shared differentially expressed genes in cancer and autoimmune disease.

BACKGROUND: Inadequate immunity caused by poor immune surveillance leads to tumorigenesis, while excessive immunity due to breakdown of immune tolerance causes autoimmune genesis. Although the function of immunity during the onset of these two processes appears to be distinct, the underlying mechanism is shared. To date, gene expression data for large bodies of clinical samples are available, but the resemblances of tumorigenesis and autoimmune genesis in terms of immune responses remains to be summed up. METHODS: Considering the high disease prevalence, we chose invasive ductal carcinoma (IDC) and systemic lupus erythematosus (SLE) to study the potential commonalities of immune responses. We obtained gene expression data of IDC/SLE patients and normal controls from five IDC databases (GSE29044, GSE21422, GSE22840, GSE15852, and GSE9309) and five SLE databases (GSE154851, GSE99967, GSE61635, GSE50635, and GSE17755). We intended to identify genes differentially expressed in both IDC and SLE by using three bioinformatics tools including GEO2R, the limma R package, and Weighted Gene Co-expression Network Analysis (WGCNA) to perform function enrichment, protein-protein network, and signaling pathway analyses. RESULTS: The mRNA levels of signal transducer and activator of transcription 1 (STAT1), 2'-5'-oligoadenylate synthetase 1 (OAS1), 2'-5'-oligoadenylate synthetase like (OASL), and PML nuclear body scaffold (PML) were found to be differentially expressed in both IDC and SLE by using three different bioinformatics tools of GEO2R, the limma R package and WGCNA. From the combined databases in this study, the mRNA levels of STAT1 and OAS1 were increased in IDC while reduced in SLE. And the mRNA levels of OASL and PML were elevated in both IDC and SLE. Based on Kyoto Encyclopedia of Genes and Genomes pathway analysis and QIAGEN Ingenuity Pathway Analysis, both IDC and SLE were correlated with the changes of multiple components involved in the Interferon (IFN)-Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway. CONCLUSION: The expression levels of STAT1 and OAS1 manifest the opposite expression tendency across cancer and autoimmune disease. They are components in the IFN-JAK-STAT signaling pathway related to both tumorigenesis and autoimmune genesis. STAT1 and OAS1-associated IFN-JAK-STAT signaling could explain the commonalities during tumorigenesis and autoimmune genesis and render significant information for more precise treatment from the point of immune homeostasis.

Expression of substance P, neurokinin 1 receptor, Ki-67 and pyruvate kinase M2 in hormone receptor negative breast cancer and evaluation of impact on overall survival.

BACKGROUND: Chronic inflammation is a hallmark of cancer, and it can be stimulated by many factors. Substance P (SP), through binding to neurokinin 1 receptor (NK1R), and pyruvate kinase M2 (PKM2) play critical roles in cancer development and progression via modulating the tumor microenvironment. This study aimed to investigate the prognostic significance of SP and PKM2 in combination with NK1R and Ki-67 in hormone receptor negative (HR-ve) breast cancer. METHODS: Immunohistochemical expression levels of SP, NK1R, PKM2, and Ki-67 were measured in 144 paraffin-embedded breast cancer tissues (77 h -ve and 67 h + ve). SP, NK1R, and PKM2 were scored semiquantitatively, while Ki-67 was obtained by the percentage of total number of tumor cells with nuclear staining. The optimal cutoff value for SP, NK1R, PKM2, and Ki-67 were assessed by Cutoff Finder. RESULTS: High SP expression in HR -ve breast cancer was associated with TNM stage (p = 0.020), pT stage (p = 0.035), pN stage (p = 0.002), axillary lymph node metastasis (p = 0.003), and NK1R expression level (p = 0.010). In HR + ve breast cancer, SP expression was associated with HER2 status (p = 0.001) and PKM2 expression level (p = 0.012). Regarding PKM2 expression level, it significantly associated with HER2 status (p = 0.001) and history of DCIS (p = 0.046) in HR-ve tumors, and with HER2 status (p < 0.001) and SP expression level (p = 0.012) in HR + ve tumors. Survival analysis revealed that high SP level negatively impacted overall survival in HR-ve tumors that had low NK1R level (p = 0.021). Moreover, high SP negatively impacted overall survival in HR-ve tumors that had low Ki-67 level (p = 0.005). High PKM2 negatively impacted overall survival in HR-ve cases with low SP (p = 0.047). CONCLUSION: Combined expression levels of SP with NK1R or Ki-67, and PKM2 with SP could be used to predict survival in breast cancer patients with HR-ve tumors. Our findings suggest a role of SP/NK1R pathway and PKM2 in HR-ve breast cancer pathogenesis which should be further investigated to unveil the underlying molecular mechanisms.

Feasibility of Quantitative MRI Using 3D-QALAS for Discriminating Immunohistochemical Status in Invasive Ductal Carcinoma of the Breast.

BACKGROUND: Two-dimensional synthetic MRI of the breast has limited spatial coverage. Three-dimensional (3D) synthetic MRI could provide volumetric quantitative parameters that may reflect the immunohistochemical (IHC) status in invasive ductal carcinoma (IDC) of the breast. PURPOSE: To evaluate the feasibility of 3D synthetic MRI using an interleaved Look-Locker acquisition sequence with a T2 preparation pulse (QALAS) for discriminating the IHC status, including hormone receptor (HR), human epidermal growth factor receptor 2 (HER 2), and Ki-67 expression in IDC. STUDY TYPE: Prospective observational study. POPULATION: A total of 33 females with IDC of the breast (mean, 52.3 years). FIELD STRENGTH/SEQUENCE: A 3-T, 3D-QALAS gradient-echo and fat-suppressed T1-weighted 3D fast spoiled gradient-echo sequences. ASSESSMENT: Two radiologists semiautomatically delineated 3D regions of interest (ROIs) of the whole tumors on the dynamic MRI that was registered to the synthetic T1-weighted images acquired from 3D-QALAS. The mean T1 and T2 were measured for each IDC. STATISTICAL TESTS: Intraclass correlation coefficient for assessing interobserver agreement. Mann-Whitney U test to determine the relationship between the mean T1 or T2 and the IHC status. Multivariate logistic regression analysis followed by receiver operating characteristics (ROC) analysis for discriminating IHC status. A P value <0.05 was considered statistically significant. RESULTS: The interobserver agreement was good to excellent. There was a significant difference in the mean T1 between HR-positive and HR-negative lesions, while the mean T2 value differed between HR-positive and HR-negative lesions, between the triple-negative and HR-positive or HER2-positive lesions, and between the Ki-67 level > 14% and ≤ 14%. Multivariate analysis showed that the mean T2 was higher in HR-negative IDC than in HR-positive IDC. ROC analysis revealed that the mean T2 was predictive for discriminating HR status, triple-negative status, and Ki-67 level. DATA CONCLUSION: 3D synthetic MRI using QALAS may be useful for discriminating IHC status in IDC of the breast. EVIDENCE LEVEL: 1. TECHNICAL EFFICACY: Stage 2.

Predicting Upgrade of Ductal Carcinoma In Situ to Invasive Breast Cancer at Surgery With Ultrafast Imaging.

BACKGROUND. Biopsy-proven ductal carcinoma in situ (DCIS) lesions are often upgraded to invasive cancer at surgery. Therefore, accurate prediction of the likelihood of invasion is helpful for surgical planning, including the need for sentinel lymph node biopsy (SLNB). OBJECTIVE. The purpose of the present study was to investigate whether kinetic features of clinically available ultrafast MRI (UF-MRI) can predict upgrade of biopsy-proven DCIS to invasive cancer at surgical excision. METHODS. Consecutive patients with biopsy-proven pure DCIS lesions who underwent UF-MRI with conventional dynamic contrast-enhanced MRI (DCE-MRI) and subsequently underwent surgery between August 2019 and January 2021 were identified. Patient and lesion characteristics, biopsy method and pathology, and lesion features on mammography, ultrasound, DCE-MRI, and UF-MRI were assessed to determine predictors of upgrade to invasive cancer. The Fisher exact test and Kruskal-Wallis test were used for association analysis. RESULTS. In 68 patients (median age, 52.0 years; range, 31-79 years) with 68 biopsy-proven pure DCIS lesions, 26 lesions (38%) were upgraded from in situ to invasive cancer. An upgrade of DCIS to invasive cancer was significantly associated with a shorter time to enhancement (TTE) on preoperative UF-MRI (p = .03), with a threshold of 11 seconds providing maximum specificity (50%) and sensitivity (76%) for upgrade. Larger lesion size on DCE-MRI (p = .001) and mammography (p = .04) was also significantly associated with upgrade; an optimal predictive threshold of 4.4 cm on DCE-MRI yielded sensitivity of 88% and specificity of 56%. No other specific variables were significantly associated with upgrade after surgery. Logistic regression of selected features combined with TTE produced a higher AUC (0.85) in predicting upgrade to invasive disease than did each factor alone, but this result was not statistically significant. CONCLUSION. Preoperative UF-MRI TTE and lesion size on DCE-MRI and mammography show potential in predicting upgrade of DCIS to invasive cancer at surgery. CLINICAL IMPACT. UF-MRI provides useful information that can be used in surgical planning, including determination of the need to perform SLNB.

Clinicopathological characteristics and prognosis of metaplastic breast cancer versus triple-negative invasive ductal carcinoma: a retrospective analysis.

BACKGROUND: Metaplastic breast cancer(MBC) is a specific pathological type of invasive breast cancer. There are few studies related to MBC due to its rarity. This study aimed to analyse the differences in clinicopathological characteristics and prognosis between Metaplastic breast cancer and triple-negative invasive ductal carcinoma (TN-IDC). METHODS: We retrospectively compared the clinicopathological characteristics of patients diagnosed with MBC and TN-IDC at the Fourth Hospital of Hebei Medical University between 2011 and 2020 in a 1:2 ratio. The log-rank test was used to compare the two groups' disease-free survival (DFS) and overall survival (OS). For MBCs, we performed univariate and multivariate analyses using the Cox proportional hazards model to determine the characteristics that impacted OS and DFS. RESULTS: A total of 81 patients with MBC and 162 patients with TN-IDC were included in this study. At initial diagnosis, MBC patients had larger tumour diameters(P = 0.03) and fewer positive lymph nodes (P = 0.04). Patients with MBC were more likely to have organ metastases after surgery (P = 0.03). Despite receiving the same treatment, MBC patients had worse DFS (HR = 1.66, 95%CI 0.90-3.08, P = 0.11) and OS (HR = 1.98, 95% CI 1.03-3.81, P = 0.04), and OS was statistically significant. Positive lymph nodes at initial diagnosis were associated with worse DFS (HR = 3.98, 95%CI 1.05-15.12, P = 0.04) and OS (HR = 3.70, 95%CI 1.03-13.34, P = 0.04) for patients with MBC. The efficacy of platinum-based agents is insensitive for MBC patients receiving chemotherapy. In addition, patients treated with preoperative chemotherapy had worse DFS compared to patients treated with postoperative chemotherapy (HR = 3.51, 95%CI 1.05-11.75, P = 0.04). CONCLUSIONS: The clinicopathological characteristics and prognosis of MBC and TN-IDC differ in many ways. Further studies are required to determine suitable treatment guidelines for patients with MBC.

Histological and electron microscopic features of the extracellular matrix of invasive breast ductal carcinoma of no special type. Report of 5 cases and literature review.

Invasive ductal carcinoma of no special type is the most common type of breast cancer. In light of the above, many authors have reported the histological and electron microscopic characteristics of these tumors. On the other hand, a limited number of works exist where the authors have concentrated on investigating the extracellular matrix. This article presents data received as the results of light and electron microscopic examination of the extracellular matrix, angiogenesis, and cellular microenvironment of invasive breast ductal carcinoma of no special type. The authors have shown that the processes of stroma formation in the IDC NOS type are associated with the presence of fibroblasts, macrophages, dendritic cells, lymphocytes, and other cells. It was also shown the detailed interaction of the above cells with each other, as well as with vessels and fibrillar proteins such as collagen and elastin. The microcirculatory component is characterized by histophysiological heterogeneity, which manifests as the activation of angiogenesis, relative vascular differentiation, and regression of individual microcirculation components.

Distant metastasis and prognostic factors in patients with invasive ductal carcinoma of the breast.

OBJECTIVE: To explore the risk factors and prognostic factors of invasive ductal carcinoma (IDC) and to predict the survival of IDC patients with metastasis. METHOD: We used multivariate logistic regression to identify independent risk factors affecting metastasis in IDC patients and used Cox regression to identify independent prognostic factors affecting the overall survival of patients with metastasis. Nomogram was used to predict survival, while C-index and calibration curves were used to measure the performance of nomogram. Kaplan-Meier method was used to calculate the survival curves of patients with different independent prognostics factors and different metastatic sites, and the differences were compared by log-rank test. The data of our study were obtained from the Surveillance, Epidemiology and End Results cancer registry. RESULT: Our study included 226,094 patients with IDC. In multivariate analysis, independent risk factors of metastasis included age, race, marital status, income, geographic region, grade, T stage, N stage, subtype, surgery and radiotherapy. Independent prognostic factors included age, race, marital status, income, geographic region, grade, T stage, N stage, subtype, surgery and chemotherapy. We established a nomogram, of which the C-index was 0.701 (0.693, 0.709), with the calibration curves showing that the disease-specific survival between actual observation and prediction had a good consistency. The survival curves of different metastatic patterns were significantly different (log-rank test: χ2  = 18784, p < 0.001; χ2  = 47.1, p < 0.001; χ2  = 20, p < 0.001). CONCLUSION: The nomogram we established may provide risk assessment and survival prediction for IDC patients with metastasis, which can be used for clinical decision-making and reference.

Acute annular outer retinopathy preceded by invasive ductal breast carcinoma: a case report.

BACKGROUND: Acute annular outer retinopathy (AAOR) is an uncommon disease. To date, there are few documented cases in the literature. Our case report is the first to describe a case of acute annular outer retinopathy in a patient with invasive ductal breast carcinoma. CASE PRESENTATION: The patient presented with photopsias and visual loss approximately 3 weeks prior to a diagnosis of invasive ductal breast carcinoma. We have documented the outer annular white ring seen in the acute phase of this disease and correlate it anatomically with Spectral-domain optical coherence tomography (SD-OCT) imaging. We identified RPE atrophy with nodular hyperreflectivity and loss of ellipsoid layer within the white annular ring with corresponding visual field loss. Fundus autofluorescence correlated with structural alterations seen on SD-OCT and showed both presumed active hyperautofluorescent zones with patchy hypoautofluorescent zones of atrophy and a classic annular hyperautofluorescent border. This case provides additional information about the natural history of this rare entity and its prognosis and varied presentation. CONCLUSIONS: The authors report a single case of acute annular outer retinopathy in a patient with invasive ductal breast carcinoma with the corresponding SD-OCT, fundus autofluorescence and visual field findings, during the acute phase of the disease. These findings provide new insight into the characteristic features, etiology and progression of this rare disease.

Does ARFI elastography complement B-mode ultrasonography in the radiological diagnosis of idiopathic granulomatous mastitis and invasive ductal carcinoma?

BACKGROUND: Idiopathic granulomatous mastitis (IGM) is a chronic, unpleasant autoimmune inflammatory condition and is clinically and radiologically often confused with breast malignancy. PURPOSE: To investigate the contributions of qualitative and quantitative aspects of acoustic radiation force impulse (ARFI) elastography to the differential diagnosis between IGM and invasive ductal carcinoma (IDC) in the breast. MATERIAL AND METHODS: Ninety-four women with IDC and 39 with IGM were included in the study. Shear wave velocity (SWV) was calculated for all lesions using quantitative elastography. Next, each lesion's correspondence on qualitative elastographic images to those on the B-mode images was evaluated: pattern 1, no findings on elastography images; pattern 2, lesions that were bright inside; pattern 3, lesions that contained both bright and dark areas; and pattern 4, lesions that were dark inside. Pattern 4 was subdivided into 4a (dark area same size as lesion) and 4b (dark area larger than lesion size). Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were calculated. RESULTS: The mean SWV based on ARFI elastography was 3.78 ± 1.26 m/s for IGM and 5.34 ± 1.43 m/s for IDC lesions (P < 0.05). Based on qualitative ARFI elastography, IDC lesions were mostly classified as pattern 4b, while IGM lesions were mostly classified as pattern 1 or 2 (P = 0.01). Evaluation of both the qualitative and quantitative aspects of ARFI elastography yielded a sensitivity of 89% and specificity of 84%. CONCLUSION: ARFI elastography may facilitate the differential diagnosis between IGM and IDC.

Sigmoid model analysis of breast dynamic contrast-enhanced MRI: Distinguishing between benign and malignant breast masses and breast cancer subtype prediction.

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is performed to distinguish between benign and malignant lesions by evaluating the changes in signal intensity of the acquired image (kinetic curve). This study aimed to verify whether the existing breast DCE-MRI analyzed by the sigmoid model can accurately distinguish between benign and invasive ductal carcinoma (IDC) and predict the subtype. A total of 154 patients who underwent breast MRI for detailed breast mass examinations were included in this study (38 with benign masses and 116 with IDC. The sigmoid model involved the acquisition of images at seven timepoints in 1-min intervals to determine the change in signal intensity before and after contrast injection. From this curve, the magnitude of the increase in signal intensity in the early phase, the time to reach the maximum increase, and the slopes in the early and late phases were calculated. The Mann-Whitney U-test was used for the statistical analysis. The IDC group exhibited a significantly larger and faster signal increase in the early phase and a significantly smaller rate of increase in the late phase than the benign group (P < 0.001). The luminal A-like group demonstrated a significantly longer time to reach the maximum signal increase rate than other IDC subtypes (P < 0.05). The sigmoid model analysis of breast DCE-MRI can distinguish between benign lesions and IDC and may also help in predicting luminal A-like breast cancer.

miR-646/TET1 mediated demethylation of IRX1 promoter upregulates HIST2H2BE and promotes the progression of invasive ductal carcinoma.

BACKGROUND: This study aimed to explore role of miR-646 in breast IDC. METHODS: miR-646, TET1, IRX1, and HIST2H2BE expression was detected by RT-qPCR and/or Western blot analysis. The methylation status of IRX1 promoter region was evaluated by methylation specific PCR. ChIP assay was used to determine the enrichment of TET1 at IRX1 promoter region. Loss- and gain-of functions were performed to determine the roles of miR-646, TET1, IRX1, and HIST2H2BE in cell proliferation, migration, invasion, and apoptosis. The tumor growth, volume, weight, and apoptosis status were measured. RESULTS: miR-646 was upregulated while TET1 was downregulated in IDC tissues. miR-646 targeted TET1. Downregulated TET1 impairs demethylation of IRX1 promoter region resulting in reduced expression of IRX1, which subsequently leads to upregulation of HIST2H2BE in IDC. Consequently, elevated HIST2H2BE promotes progression of IDC. CONCLUSION: Our study has demonstrated that miR-646 facilitates the tumorigenesis of IDC via regulating TET1/IRX1/HIST2H2BE axis.

[Young mammary Paget's disease patients with underlying breast invasive ductal carcinoma: clinicopathological features and prognosis].

Objective: To investigate the clinicopathological factors and prognostic status of young Mammary Paget's disease (MPD) patients with invasive ductal carcinoma (IDC). Methods: In this study, we defined the age at diagnosis below 40 years old as young patients, and retrospectively analyzed data from 123 MPD-IDC patients who were admitted at the Cancer Hospital Chinese Academy of Medical Sciences from June 2002 to February 2019. Patients were divided into the young group (≤40 years old, 15 cases) and the old group (>40 years old, 108 cases) according to the age of onset, and the clinicopathological characteristics and prognosis of the two groups were compared. Cox regression model analysis was used to analyze the prognosis influencing factors. Results: The proportions of patients in the young group with non-menopausal, axillary lymph node metastasis, and Ki-67 index ≥15% were 93.3% (14/15), 73.3% (11/15), and 86.7% (13/15), respectively, which were higher than those in the old group [45.4% (49/108), 39.8%(43/108), and 60.2% (65/108), respectively] , with statistically significant differences (P<0.05). At an average follow-up of 63.2 months, patients in the young group had a significantly shorter disease-free survival (DFS) compared with that of the old group (P=0.012), while the difference in overall survival (OS) between the two groups was not statistically significant (P=0.161). Multifactorial Cox regression analysis showed that axillary lymph node status was an independent influencing factor on OS (HR=3.339, 95% CI: 1.121-9.943) in patients with MPD-IDC, while age was not. Conclusion: Compared with the old group, young patients with MPD-IDC have a higher incidence of axillary lymph node metastasis, high Ki-67 expression, and a shorter DFS, but age is not an independent influencing factor on DFS or OS in patients with MPD-IDC.