Diagnosis Of Invasive Ductal Carcinoma Research Articles

A Study Protocol on Assessment of Epidermal Growth Factor Receptor (EGFR) Signalling Pathway as a Predictive Molecular Marker in Triple-Negative Invasive Ductal Carcinoma of Breast

Background: Breast cancer is the leading cause of cancer-related deaths worldwide. The Indian scenario is no different for the breast cancer mortality. Breast cancers have occupied the prominence not only for their incidence but the pace too. The researchers have studied numerous pathways vastly and widely in the past two decades to ascertain the prognosis and treatment outcome determinants popularly called predictive markers for breast cancer. One such cell signalling pathway that has raised the hope by assessing success for breast cancer is the Epidermal Growth Factor Receptor (EGFR) signalling pathway for a molecular subtype of Triple-Negative Breast Cancer (TNBC), which is challenging to treat therapeutically. This study aims to assess the EGFR pathway and its sub pathways in Triple-negative breast carcinoma (TNBC) and correlate the abnormalities of expressions in the EGFR pathway in TNBC for its therapeutic implications.
 Materials and Methods: This will be an observational cross-sectional study. Forty cases of TNBC will be selected. There will be 10 cases each in 31-40 years, 41-50 years, 51-60 years, and 61 years onwards. Cases will undergo histological diagnosis of invasive ductal carcinoma, Immunohistochemistry for ER, PR, and Her2neu, IHC for EGFR, BRAF, Kras, and MAP kinase on histological sections, Polymerase chain reaction( PCR) for Kras. Data will be collected and analyzed using appropriate statistical tests.
 Results: A significant correlation of EGFR, BRAF, KRAS, and MAP kinase is expected in the pathogenesis of triple-negative invasive ductal carcinoma.
 Conclusion: The results can be put to the commercial advantage for clinical trials of the new drug development targeting anti-EGFR and other antibodies.

Ultrasound Imaging Morphology is Associated with Biological Behavior in Invasive Ductal Carcinoma of the Breast.

Objectives:Ultrasound (US) is commonly used for diagnostic evaluation of breast lesions. The objective of this study was to investigate the association between US imaging morphology from routine radiologists’ interpretation and biological behavior such as receptor status and tumor grade determined from histopathology in invasive ductal carcinoma (IDC).Material and Methods:This retrospective study included 453 patients with pathology-verified diagnosis of IDC who had undergone US imaging and had surgery over a 5-year period. US and surgical pathology reports were reviewed and compiled. Correlation analyses and age-adjusted multivariable models were used to determine the association between US imaging morphology and receptor status, tumor grade, and germ line mutation of the breast cancer genes (BRCA1 and BRCA2). The odds ratio (OR), area under receiver operating characteristic curve (AUC), and 95% confidence intervals (CI) were obtained.Results:The likelihood for high-grade cancer increased with size (OR: 1.066; CI: 1.042–1.091) and hypo-echogenicity (OR: 2.044; CI: 1.337–3.126), and decreased with angular or spiculated margins (OR: 0.605; CI: 0.393–0.931) and posterior acoustic shadowing (OR: 0.352; CI: 0.238–0.523). These features achieved an AUC of 0.799 (CI: 0.752–0.845) for predicting high-grade tumors. The likelihood for Estrogen Receptor-positive tumors increased with posterior acoustic shadowing (OR: 3.818; CI: 2.206–6.607), angulated or spiculated margins (OR: 2.596; CI: 1.159–5.815) and decreased with US measured tumor size (OR: 0.959; CI: 0.933–0.986) and hypoechoic features (OR: 0.399; CI: 0.198– 0.801), and achieved an AUC of 0.787 (CI: 0.733–0.841). The likelihood for Progesterone Receptor-positive tumors increased with posterior acoustic shadowing (OR: 2.732; CI: 1.744–4.28) and angulated or spiculated margins (OR: 2.618; CI: 1.412–4.852), and decreased with US measured tumor size (OR: 0.961; CI: 0.937–0.985) and hypoechoic features (OR: 0.571; CI: 0.335–0.975), and achieved an AUC of 0.739 (CI: 0.689–0.790). The likelihood for Human epidermal growth factor receptor 2-positive tumors increased with heterogeneous echo texture (OR: 2.141; CI: 1.17– 3.919) and decreased with angulated or spiculated margins (OR: 0.408; CI: 0.177–0.944), and was marginally associated with hypoechoic features (OR: 2.101; CI: 0.98–4.505) and circumscribed margins (OR: 4.225; CI: 0.919–19.4). The model with the aforementioned four US morphological features and achieved an AUC of 0.686 (CI: 0.614–0.758). The likelihood for triple-negative breast cancers increased with hypo-echogenicity (OR: 2.671; CI: 1.249–5.712) and decreased with posterior acoustic shadowing (OR: 0.287; CI: 0.161–0.513), and achieved an AUC of 0.739 (CI: 0.671– 0.806). No statistical association was observed between US imaging morphology and BRCA mutation.Conclusion:In this study of over 450 IDCs, significant statistical associations between tumor grade and receptor status with US imaging morphology were observed and could serve as a surrogate imaging marker for the biological behavior of the tumor.

Breast Invasive Ductal Carcinoma Diagnosis with A Three-Mirna Panel in Serum

Aim: Breast cancer, especially invasive ductal carcinoma (IDC), is the cause of a great clinical burden. miRNA could be considered as a noninvasive biomarkers for IDC diagnosis. Materials & methods: Two hundred and sixty participants (135 IDC patients and 125 healthy controls) were enrolled in a three-cohort study. The expression of 28 miRNAs in serum were detected with quantitative reverse transcription-PCR. Bioinformatic analysis was used for predicting the target genes of three selected miRNAs. Results: The expression level of seven miRNAs (miR-9-5p, miR-34b-3p, miR-1-3p, miR-146a-5p, miR-20a-5p, miR-34a-5p, miR-125b-5p) was discrepant at the validation cohort. Through statistical test, a three-miRNA panel (miR-9-5p, miR-34b-3p, miR-146a-5p) was significant for IDC diagnosis (AUC=0.880, sensitivity=86.25%, specificity=81.25%). Conclusion: The three-miRNA panel in serum could be used as a noninvasive biomarker in the diagnosis of IDC.

Deep assisted dense model based classification of invasive ductal breast histology images

Invasive Ductal Carcinoma (IDC) is one of the types of breast cancer which is mostly diagnosed in the female. The diagnosis of IDC becomes a challenging task when a microscopic cell line structure is classified manually which requires a lot of expertise. Literature suggests a lot of computer-assisted deep models that prove as a helping hand for radiologists. But one limitation identified in most of the deep models is the vanishing gradient problem. This paper presents a dense model that overcomes the limitation of the vanishing gradient problem and outperforms in terms of classification accuracy with respect to other deep models. In addition, the proposed methodology also focused on the feature reusability with an optimized number of parameters for IDC histology image classification. The proposed method uses the CLAHE as a preprocessing method with 9 layers of dense deep architecture for experimentation purposes. The proposed model uses the base architecture of Densenet-169 with some proposed layer modifications to solve the targeted problem. While during the experimentation, validation of the proposed model is found satisfactory with an accuracy of 98.21%. The test set results are provided on the Kaggle under leaderboard with an AUC–ROC result of 97.54%. The experimentation result gained a classification accuracy of around 1.21% with respect to other methods present in the literature.

Neoadjuvant Chemotherapy or Endocrine Therapy for Invasive Ductal Carcinoma of the Breast With High Hormone Receptor Positivity and Human Epidermal Growth Factor Receptor 2 Negativity

Although neoadjuvant endocrine therapy (NET) is an alternative to chemotherapy for strongly hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (ERBB2)-negative breast cancer, evidence is currently lacking regarding the probable survival outcomes of NET in comparison with those of neoadjuvant chemotherapy (NACT) for this cancer. To evaluate all-cause mortality among patients with strongly HR-positive and ERBB2-negative breast cancer treated with NET vs NACT. This cohort study included patients with a diagnosis of invasive ductal carcinoma (IDC) with strong HR positivity and ERBB2 negativity, treated between January 1, 2009, and December 31, 2016, with follow-up from the index date (ie, date of IDC diagnosis) to December 31, 2018. The data came from the Taiwan Cancer Registry Database. Data were analyzed from January to November 2020. NET vs NACT for IDC with strong HR positivity and ERBB2 negativity. The primary end point was all-cause mortality. Propensity score matching was performed, and Cox proportional hazard models were used to analyze all-cause mortality among patients undergoing different neoadjuvant treatments. A total of 640 patients (297 [46.4%] aged 20-49 years) undergoing NET (145 patients [22.7%]) or NACT (495 patients [77.3%]) were eligible for further analysis. In the multivariate Cox regression analyses, the adjusted hazard ratio (aHR) for all-cause mortality among the NET cohort compared with the NACT cohort was 2.67 (95% CI, 1.95-3.51; P < .001). The aHRs for age were 1.13 (95% CI, 1.03-2.24), 1.25 (95% CI, 1.13-2.45), and 1.37 (95% CI, 1.17-3.49) for all-cause mortality among patients aged 50 to 59, 60 to 69, and 70 years or older, respectively, compared with those aged 20 to 49 years (P = .002); the aHR for all-cause mortality among premenopausal women was 1.35 (95% CI, 1.13-1.56) compared with postmenopausal women (P < .001); and that of patients with a Charlson Comorbidity Index score of 2 or greater was 1.77 (1.37-2.26) compared with those with a score of 0 (P < .001). The aHRs of all-cause mortality for clinical tumor stage 2, 3, and 4 compared with 1 were 1.84 (95% CI, 1.07-3.40), 1.97 (95% CI, 1.03-3.77), and 2.49 (95% CI, 1.29-4.81), respectively (P = .009). The aHRs for all-cause mortality by clinical nodal (cN) stages were 1.49 (95% CI, 1.13-1.99) and 1.84 (95% CI, 1.31-2.61) for cN stage 1 and cN stages 2 or 3, respectively, compared with cN stage 0 (P = .005); those for differentiation were 1.77 (95% CI, 1.24-2.54) and 2.31 (95% CI, 1.61-3.34) for differentiation grade 2 and differentiation grade 3, respectively, compared with differentiation grade 1 (P < .001). The findings of this study suggest that for patients with strongly HR-positive and ERBB2-negative IDC, NACT may be considered the first choice for neoadjuvant treatment.

Our sentinel lymph node experience in patients diagnosed with DCIS and microinvasive breast carcinoma

Aim: Along with the increased availability of radiologic imaging methods, early identification of tumor tissue, and patient surveillance programs; ductal carcinoma in situ (DCIS) and microinvasive DCIS became more commonly identified in the tru-cut biopsy specimens and resected samples of patients. Pathological examinations of the excision materials from these patients reveal invasive tumors, microinvasions or DCIS alone. Recently, it has become debatable whether to perform a sentinel lymph node biopsy (SLNB) in patients diagnosed with DCIS or microinvasive DCIS. In this present study, we evaluated the diagnosis made by examining the excision material, any presence of lymph node metastases, and the relationship of hormone profile to the presence of metastases in the patients diagnosed with DCIS or microinvasive DCIS by the examination of tru-cut biopsy specimens. Based on our study results, we discussed the requirement for SLNB in patients with a tru-cut diagnosis of DCIS or microinvasive DCIS.Materials and Methods: The study included 172 patients, who underwent surgical excision and SLNB after receiving a tru-cut biopsy diagnosis of DCIS and microinvasive DCIS in our hospital from the year 2010 to 2018.Results: Tru-cut biopsy diagnoses were DCIS and microinvasive DCIS in 69.8% (120 patients) and 30.2% (52 patients) respectively. SLNB metastases were identified in 35.8% (n=43) of the DCIS positive patients and 44.2% (n=23) in the microinvasive DCIS positive patients. The diagnosis of invasive ductal carcinoma after mastectomy was made at a rate of 90.0% (n=108) among the DCIS positive patients and 92.3% (n=48) among the microinvasive DCIS positive patients. Conclusion: SLNB metastases were found in 35.8% (n=43) and 44.2% (n=23) of the DCIS positive patients and microinvasive DCIS positive patients, respectively. We conclude that SLNB should be favorably proper to perform in the patients with tru-cut diagnoses of DCIS and microinvasive DCIS because a high rate of SLNB metastases was detected in our DCIS and microinvasive DCIS patients and a high rate of invasive ductal carcinoma diagnosis was made after examining the excision material of these patients.

Detecting early onset of chemotherapy‐related cardiac dysfunction in breast cancer patients in the West Virginian population using a novel panel of biomarkers

BackgroundCardiotoxicity has been intricately linked in breast cancer patients receiving anthracyclines therapy in the clinical setting. The cumulative line of evidence has demonstrated that cardiotoxic manifestation associated with breast cancer treatment increases patients’ susceptibility to myocardial injury, reduction in left ventricular ejection fraction and complications associated with heart failure. There is currently no standardized, minimally invasive, cost effective and clinically verified procedure to monitor cardiotoxicity post‐anthracycline therapy initiation, and to detect early onset of irreversible cardiovascular complications. An important role of altered levels of serum biomarkers and circulating miRNAs have been implicated in modulating cardiac vasculature and cardiac damage.HypothesisThis study aims to create a panel of novel biomarkers and circulating miRNAs associated with cardiotoxicity, to assess the correlation between anthracycline agents and development of cardiac dysfunction, which will allow to monitor and detect early‐onset of chemotherapy related cardiac dysfunction.Materials and MethodsA total of 17 female patients with a clinical diagnosis of invasive ductal carcinoma were enrolled for the study. Blood was withdrawn and echocardiography assessment was performed at baseline (prior to initiation of anthracyclines), 3months and 6months post‐initiation of anthracycline agents. Subsequently, a total of 17 healthy controls were also recruited for the study without any form of cancer or cardiovascular complications. Enzyme Linked Immunosorbent Assays (ELISA) were performed for biomarker analysis and RT‐PCR was performed for expression of circulating miRNA levels.ResultsOur results showed that interleukin‐6 (IL‐6), matrix metalloproteinase ‐2 (MMP2) and ‐9 (MMP9), myeloperoxidase (MPO) and topoisomerase II beta (TOP2B) were significantly upregulated in serum obtained at 3months and 6months study interval post anthracycline initiation, as compared to baseline and healthy controls (p&lt;0.01). The circulating levels of miR‐34a, miR‐208b, miR‐126, miR‐150, miR‐423 and miR‐499a were positively correlated and showed elevated levels at 3months and even higher in 6months study interval, while levels of miR‐29a were reduced at 3months, and much lower at 6months, as compared to control group (p&lt;0.01). Assessment of echocardiographic measurements exhibited greater extent of cardiac dysfunction at 3months and 6month study interval.ConclusionOur results support the clinical application of these serum biomarkers and circulating miRNAs to develop a panel for early diagnosis of chemotherapy related cardiac dysfunction which will enable early detection of disease progression and management of irreversible cardiac damage.Support or Funding InformationThis work was supported by the Brickstreet Foundation (J.I.S.).

Trastuzumab-Induced Severe Thrombocytopenia: A Case Report and Literature Review

We present a 29-year-old woman with pT2N0M0 breast cancer, histological diagnosis of invasive ductal carcinoma, ER and PR low positive, and HER-2 (3+). The patient developed trastuzumab-induced thrombocytopenia in 6 hours after an intravenous infusion of trastuzumab at the second cycle of trastuzumab treatment with the symptom of abnormal uterine bleeding. Laboratory exam revealed a sharp drop of platelet count down to 3×109/L. With the treatment of single-donor platelet transfusions, glucocorticoids, oxytocin and thrombopoietic drugs, the platelet count recovered completely in 11 days. This case was confirmed to be severe thrombocytopenia induced by trastuzumab, and retreatment with trastuzumab was not attempted. With increasing clinical utilization of trastuzumab, clinicians are likely to encounter more life-threatening trastuzumab induced severe thrombocytopenia. By this case report and literature review, we hope to increase the awareness, attach the attentions to this condition, and help with the effective treatment.

Aldehyde dehydrogenase-1 positivity is associated with ER negativity in patients with invasive ductal carcinoma of the breast.

Cancer stem cells (CSCs) are self-renewable and can be differentiated into different cell types. They play an important role in oncogenic signaling pathways, tumor cell heterogeneity, metastasis, and therapeutic resistance. Aldehyde dehydrogenase 1 (ALDH1) was identified as a specific marker for breast CSCs. The study included a total of 105 patients with a diagnosis of invasive ductal carcinoma (IDC) who underwent mastectomy and with sufficient pathology material for histopathological examination. Patient demographics, tumor location, tumor diameter, the presence of lymphovascular and perineural invasion and lymph node metastasis, surgical margin status, and immunohistochemistry (IHC) staining results were obtained from patients' records. The tumors were classified into IHC-based molecular subtypes according to the St. Gallen Consensus Conference in 2013. A four-tiered scoring system was used based on ALDH1 staining percentage in tumor cells. The tumor was determined as positive if the score was 2 or higher. Clinical, histopathological findings, and ALDH1 staining results were correlated. Twenty-five cases (23.8%) were ALDH1 positive. The ALDH1 positive group compared to the negative group was found to be associated with ER negativity (p = 0.044), but there was no correlation with other clinical and histopathological findings. ALDH1-positive IDCs may be less sensitive to hormonal therapy and associated with aggressive behavior.

Analysis of variators in the brca1 and brca2 genes by ngs in patients from central brazil with suspected hboc syndrome: a new pathogenic variant identified

About 10‒15% of breast cancer cases are due to deleterious germ changes, more than half of which are located in the BRCA1 or BRCA2 genes. The screening of variants in these genes for patients at risk brings benefits for better clinical management of the patient as well as for the prevention of disease recurrences both in the proband and in their relatives. The profile of genetic variants is little known to the Brazilian population and, to date, there are no published data for the population of the central region of the country. This study aimed to analyze the profile of pathogenic variants (VP) and of uncertain significance (VUS) in the BRCA1 and BRCA2 genes in this population. We selected 102 patients seen at Hospital das Clínicas, Universidade Federal de Goiás, with clinical diagnosis of invasive ductal carcinoma that met the criteria of the National Comprehensive Cancer Networking 2016/2 for hereditary breast and ovarian cancer syndrome. A collection of 4mL of peripheral blood was carried out and submitted to subsequent extraction of genomic DNA, carried out using the PureLink kit (Invitrogen). The genes in question had all their exon-intron regions sequenced using the MiSeq device (Illumina) and the raw data were evaluated using the Sophia DDM software. The risk of in silico pathogenicity of the VUS was analyzed by the software POLYPHEN2, MutationTaster, SIFT, ESP5400, G1000, GnomAD. Of the total of 102 patients evaluated in this study, 22 (21.56%) had PV or VUS in the BRCA1 or BRCA2 genes. Of these, 16 patients (72.81%) had pathogenic variants, eight with PV in BRCA1 (c.5266dupC (2), c.3331_3334delCAAC, c.211A&gt;G, c.3228_3229delAG, c.3700_3704delGTAAA, c.4484G&gt;T and c.5305_5306ins20) and eight with PV in BRCA2 (c.156_157insAlu, c.4829_4830delTG, c.8488-1G&gt;A, c.6405_6409delCTTAA (3), c.517-1G&gt;A, c.2808_2811delACAA). A total of 7 patients (31.8%) presented VUS in these genes, one in the BRCA1 gene (c.179A&gt;G) and five in the BRCA2 gene (c.280C&gt;T, c.811G&gt;A, 1096T&gt;G, 1441A&gt;G and c.5270A&gt;G) of which only the variant c.1441A&gt;G had low pathogenic potential in silico. A new PV still not described in the literature was also identified, variant c.5305_5306ins20 in the BRCA1 gene. These data suggest that all patients at risk in this population should be evaluated for PV or VUS in the BRCA1 and BRCA2 genes since the presence of these variants can help in the patient's prognosis and disease prevention.

Vascular Mimicry Expression in Invasive Ductal Carcinoma; A New Technique for Prospect of Aggressiveness

Background & Objective:In vascular (vasculogenic) mimicry (VM), tumoral cells mimic the endothelial cells and form the extracellular matrix-rich tubular networks. It has been proposed that VM is more extensive in aggressive tumors. This study was designed to investigate the rate of VM expression in the stromal cells of invasive ductal carcinoma (IDC) and to find its relationship with other clinicopathological factors.Methods:In this cross-sectional study, 120 patients with histopathologic diagnosis of IDC who received mastectomy were included. The VM expression was determined by immunohistochemistry (IHC). The clinicopathologic data including age, tumor size, histological grade, clinical stage, axillary lymph node metastasis, hormonal receptors, and survival were documented.Results:The mean (±SD) age of the patients was 51 (±13.83) years old. The stromal VM expression was detected in 16 of 120 patients (13.3%). Twelve specimens (75%) of positive VM expression group had grade 3 which was higher than negative VM expression group (9 cases, 8.65%; P<0.001). The VM expression showed statistically significant relationship with higher histologic grade higher clinical stage (stage 3) of the tumor (62.5% vs. 87%; P=0.003), the presence of axillary lymph node metastasis (95.6% vs. 55.8%; P<0.001), and positive HER-2 (100% vs. 31.1%; P<0.001); but not estrogen receptor (ER) or progesterone receptor (PR). However, age, tumor size and mortality rate were not significantly different among the patients with and without VM expression.Conclusion:The stromal VM expression showed significant relationship with higher stage and grade of the tumor and the presence of nodal metastasis. The VM expression in IDC can be used as a marker for tumor aggressiveness.

Mitochondrial autoimmunity and MNRR1 in breast carcinogenesis

BackgroundAutoantibodies function as markers of tumorigenesis and have been proposed to enhance early detection of malignancies. We recently reported, using immunoscreening of a T7 complementary DNA (cDNA) library of breast cancer (BC) proteins with sera from patients with BC, the presence of autoantibodies targeting several mitochondrial DNA (mtDNA)-encoded subunits of the electron transport chain (ETC) in complexes I, IV, and V.MethodsIn this study, we have characterized the role of Mitochondrial-Nuclear Retrograde Regulator 1 (MNRR1, also known as CHCHD2), identified on immunoscreening, in breast carcinogenesis. We assessed the protein as well as transcript levels of MNRR1 in BC tissues and in derived cell lines representing tumors of graded aggressiveness. Mitochondrial function was also assayed and correlated with the levels of MNRR1. We studied the invasiveness of BC derived cells and the effect of MNRR1 levels on expression of genes associated with cell proliferation and migration such as Rictor and PGC-1α. Finally, we manipulated levels of MNRR1 to assess its effect on mitochondria and on some properties linked to a metastatic phenotype.ResultsWe identified a nuclear DNA (nDNA)-encoded mitochondrial protein, MNRR1, that was significantly associated with the diagnosis of invasive ductal carcinoma (IDC) of the breast by autoantigen microarray analysis. In focusing on the mechanism of action of MNRR1 we found that its level was nearly twice as high in malignant versus benign breast tissue and up to 18 times as high in BC cell lines compared to MCF10A control cells, suggesting a relationship to aggressive potential. Furthermore, MNRR1 affected levels of multiple genes previously associated with cancer metastasis.ConclusionsMNRR1 regulates multiple genes that function in cell migration and cancer metastasis and is higher in cell lines derived from aggressive tumors. Since MNRR1 was identified as an autoantigen in breast carcinogenesis, the present data support our proposal that both mitochondrial autoimmunity and MNRR1 activity in particular are involved in breast carcinogenesis. Virtually all other nuclear encoded genes identified on immunoscreening of invasive BC harbor an MNRR1 binding site in their promoters, thereby placing MNRR1 upstream and potentially making it a novel marker for BC metastasis.

Advanced metastatic breast carcinoma in sickle cell disease

BackgroundBreast cancer is the leading cancer in women leading to over 400,000 deaths per year worldwide. It begins in the breast tissue and can metastasize to other organs if early diagnosis and treatment is not instituted. Women with sickle cell disease are usually spared from breast cancer and other solid tumours due to the tumoricidal effect of sickled erythrocytes. Breast cancers are rare among these group of patients. Despite its rare occurrence, this paper was to emphasize the need for breast cancer screening among female sickle cell disease patients who have positive family history of breast cancer.Case descriptionOO was a 30-year old woman with sickle cell disease who presented to the hospital one and half years ago with a seven months history of right breast swelling and pains. She had lost her mother to breast cancer about 15 years ago. Mammography and histology of breast biopsy confirmed diagnosis of invasive ductal carcinoma of the right breast. Financial constraint was a major challenge in managing this patient as she was unable to buy her chemotherapy. She developed features suggestive of metastasis such as seizures and hepatomegaly. She was stabilized and discharged home but we lost her to follow up. She died at home.Conclusion Breast cancer is rare among females with sickle cell disease; any of them with a family history should be routinely screened for early diagnosis and treatment.

Prognostic significance of fatty acid binding protein-4 in the invasive ductal carcinoma of the breast.

We conducted this study to identify clinico-pathologic and prognostic factors that are associated with fatty acid binding protein-4 (FABP4) and to discuss its therapeutic potentials in patients with breast cancer (BC). In a total of 75 patients with an established diagnosis of invasive ductal carcinoma of the breast, we performed a retrospective analysis of the medical records and analyzed their immunohistochemical findings. Following evaluation of baseline and clinico-pathological characteristics such as the age, immunohistochemical expressions of FABP4, TNM stage, tumor grade, lymphatic and perineural invasion, estrogen receptor (ER) and progesterone receptor (PR), disease-free survival (DFS), overall survival (OS), recurrence and death, we analyzed correlations of the expression of FABP4 with clinico-pathologic and prognostic factors. Our results showed that tumor grade and recurrence had a significant correlation with the expression of FABP4 (P = 0.002 and 0.049, respectively). Moreover, we also found that the DFS had a significant correlation with the expression of FABP4 (P = 0.049). It can therefore be concluded that the expression of FABP4 might have a prognostic value in patients with BC. But further studies are warranted to establish its potentials as a prognostic indicator.

Novel chemometrics‑assisted spectroscopic methods for diagnosis and monitoring of invasive ductal carcinoma in breast tissue.

Early diagnosis of breast cancer is extremely important because it is the most common female cancer and a leading cause of cancer death in adult women. In this study, it is aimed to create Raman mapping with developed chemometrics‑assisted Raman and FT-IR spectroscopy methods for the diagnosis of invasive ductal carcinoma (IDC) in breast tissue samples. Samples were deparaffinized and 20‑micron layers of each tissue were located on a coverslip. Mapping of both healthy and cancerous tissues were performed by exposing them to Raman laser at 532 and 758 nm while excitation was recorded at wavenumbers in range of 100-4,000 cm-1. Orthogonal partial least square (OPLS) algorithm was applied to evaluate obtained Raman spectra. Latent variable was selected to explain the whole model. Healthy and IDC tissues were accurately and precisely clustered with Raman mapping and obtained results were compared to those obtained by means of histopathology and FT-IR methods. It is claimed that the proposed method has a great potential in clustering and separating IDC tissues from the healthy ones. This novel, rapid, precise, easy and objective diagnosis method may be an alternative to conventional diagnostic methods for IDC in breast tissue (Fig. 5, Ref. 22).

LESSONS DERIVING FROM AN EASY LAPAROSCOPIC CHOLECYSTECTOMY

Gallstone is a very frequent condition, therefore laparoscopic cholecystectomy - the gold standard in the treatment of the above mentioned pathology - is the most frequent surgical intervention performed in the surgery departments in the country and abroad. At the same time, it is the laparoscopic surgery with the highest number of intraoperative incidents and accidents. Thus, in a surgical environment dominated by the stress of injuring the main bile duct, extracting the piece and sending it for the anatomical pathology examination remains on a secondary level. This is why we would like to discuss a problem related to laparoscopic cholecystectomy which is less approached in the specialty literature. Patient B, admitted to the General Surgery and Emergency Clinic III of the University Emergency Hospital of Bucharest (UESB) – medical chart (M.C.), aged 66 with a surgical history – a simple, uncomplicated laparoscopic cholecystectomy, undergone ​​two years before, with a good postoperative evolution – came to the emergency room with diffuse abdominal pain, more pronounced on the right flank. The clinical, biological and imaging evaluation performed did not reveal any pathological aspects, except for the abdominal-pelvic CT scan with a contrast agent which revealed an expansive process in the right hypochondrium lining the costal side of the liver segment VI. The tumour was surgicaly removed; the extemporaneous histopathological examination was inconclusive about the origin of the tumoral formation (adenocarcinoma of the digestive tract ). The key to the diagnosis was obtained in an administrative manner because, when the discharge letter delivered at the time of the cholecystectomy was reviewed, the absence of the result of the anatomical pathology examination of the cholecystectomy piece was noticed. The respective clinic was contacted and the result of the anatomical pathology examination was obtained, i.e. adenocarcinoma of the gallbladder. After 3 months from the surgery the patient returned with a left breast tumor with the HP diagnosis of invasive ductal carcinoma and a total Madden mastectomy wa performed. After 5 more months, surgery was necessary again for a parietal epigastic tumor - with the anatomical pathology result of cholangiocarcinoma. The author reports the case because he believes that this is further proof of the necessity of sending any cholecystectomy piece, and broadly speaking, any excised piece, for the HP examination. Moreover the patient's attention should be drawn to the necessity of returning to the clinic to take the anatomical pathology result because this result may require the reconsideration of therapeutic conduct.

Alteration in lipid composition differentiates breast cancer tissues: a 1H HRMAS NMR metabolomic study.

Breast cancer is the most frequent diagnosed cancer among women with a mortality rate of 15% of all cancer related deaths in women. Breast cancer is heterogeneous in nature and produces plethora of metabolites allowing its early detection using molecular diagnostic techniques like magnetic resonance spectroscopy. To evaluate the variation in metabolic profile of breast cancer focusing on lipids as triglycerides (TG) and free fatty acids (FFA) that may alter in malignant breast tissues and lymph nodes from adjacent benign breast tissues by HRMAS 1H NMR spectroscopy. The 1H NMR spectra recorded on 173 tissue specimens comprising of breast tumor tissues, adjacent tissues, few lymph nodes and overlying skin tissues obtained from 67 patients suffering from breast cancer. Multivariate statistical analysis was employed to identify metabolites acting as major confounders for differentiation of malignancy. Reduction in lipid content were observed in malignant breast tissues along with a higher fraction of FFA. Four small molecule metabolites e.g., choline containing compounds (Chocc), taurine, glycine, and glutamate were also identified as major confounders. The test set for prediction provided sensitivity and specificity of more than 90% excluding the lymph nodes and skin tissues. Fatty acids composition in breast cancer using in vivo magnetic resonance spectroscopy (MRS) is gaining its importance in clinical settings (Coum et al. in Magn Reson Mater Phys Biol Med 29:1-4, 2016). The present study may help in future for precise evaluation of lipid classification including small molecules as a source of early diagnosis of invasive ductal carcinoma by employing in vivo magnetic resonance spectroscopic methods.

Mammographic Evaluation of Breast Mass & Comparison with Histopathological Findings

Background: Mammography is used for the detection of breast cancer.Objective: The purpose of the present study was to evaluate the diagnostic performance of Mammography in the diagnosis of benign and malignant breast mass.Methodology: This cross-sectional type of study was carried out in the Radiology &amp; Imaging department of Sir Salimullah Medical College and Mitford Hospital, Dhaka, during July 2013 to June 2015. Patients clinically suspected as having breast mass, referred in the above mentioned hospitals and enrolled for surgical management were included in this study. Mammography were done in all these patients and they were followed up from the admission up to the post-operative tissue diagnosis of breast mass in respective pathology departments for histopathological correlation.Results: A total of 41 patients had mass among them, 3(7.3%) cases were malignant and 38(92.7%) cases were benign patients. Histopathological diagnosis of invasive ductal carcinoma, invasive lobular carcinoma and medullary carcinoma were 8(14. %), 4(7.00%) and 1(1.8%) respectively. Mammography malignant was found 14 cases out of which 10(76.9%) malignant and 4(9.1%) benign evaluated by histopathology. Mammography benign was found 43 cases out of which 3(23.1%) malignant and 40(90.9%) benign evaluated by histopathology. The sensitivity was 76.9%, specificity 90.9%, accuracy 87.7%, positive predictive values 71.4% and negative predictive values 93.0% in mammography.Conclusion: Mammography is highly sensitive, specific, reliable and useful method in the differentiation of malignant and benign breast masses.Journal of Current and Advance Medical Research 2017;4(2):53-57

Invasive Ductal Carcinoma of the Breast with Medullary Features or Medullary Carcinoma of the Breast: A Challenging Histopathological Case Report with Review of Literature

Medullary Breast carcinoma (MBC) is an infrequent type of breast cancer and is in the differential diagnosis of invasive ductal carcinoma (IDC) with medullary features. We reported a 35-year-old lady with left breast since 6 months ago. CEA tumor marker serum level and CA15-3 were within normal limits. The patient underwent the incomplete left mastectomy. Gross specimen revealed gray-yellow hemorrhagic tumor lesion with pushing border. Histopathology demonstrated highly atypical cells with lymphocytic infiltration and mainly pushing border but with infiltrative margin in few areas. The permanent diagnosis was “invasive ductal carcinoma with medullary features“. We conclude that careful histopathological evaluation and considering strict criteria is necessary for definitive diagnosis and subsequent proper treatment.

DCE-MRI Pharmacokinetic-Based Phenotyping of Invasive Ductal Carcinoma: A Radiomic Study for Prediction of Histological Outcomes.

Breast cancer is a disease affecting an increasing number of women worldwide. Several efforts have been made in the last years to identify imaging biomarker and to develop noninvasive diagnostic tools for breast tumor characterization and monitoring, which could help in patients' stratification, outcome prediction, and treatment personalization. In particular, radiomic approaches have paved the way to the study of the cancer imaging phenotypes. In this work, a group of 49 patients with diagnosis of invasive ductal carcinoma was studied. The purpose of this study was to select radiomic features extracted from a DCE-MRI pharmacokinetic protocol, including quantitative maps of ktrans, kep, ve, iAUC, and R1 and to construct predictive models for the discrimination of molecular receptor status (ER+/ER−, PR+/PR−, and HER2+/HER2−), triple negative (TN)/non-triple negative (NTN), ki67 levels, and tumor grade. A total of 163 features were obtained and, after feature set reduction step, followed by feature selection and prediction performance estimations, the predictive model coefficients were computed for each classification task. The AUC values obtained were 0.826 ± 0.006 for ER+/ER−, 0.875 ± 0.009 for PR+/PR−, 0.838 ± 0.006 for HER2+/HER2−, 0.876 ± 0.007 for TN/NTN, 0.811 ± 0.005 for ki67+/ki67−, and 0.895 ± 0.006 for lowGrade/highGrade. In conclusion, DCE-MRI pharmacokinetic-based phenotyping shows promising for discrimination of the histological outcomes.