Parameters Of Breast Cancer Research Articles

Geometric characteristics of stromal collagen fibres in breast cancer using differential interference contrast microscopy.

Breast cancer (BC) is characterised by a high level of heterogeneity, which is influenced by the interaction of neoplastic cells with the tumour microenvironment. The diagnostic and prognostic role of the tumour stroma in BC remains to be defined. Differential interference contrast (DIC) microscopy is a label-free imaging technique well suited to visualise weak optical phase objects such as cells and tissue. This study aims to compare stromal collagen fibre characteristics between in situ and invasive breast tumours using DIC microscopy and investigate the prognostic value of collagen parameters in BC. A tissue microarray was generated from 200 cases, comprising ductal carcinoma in situ (DCIS; n=100) and invasive tumours (n=100) with an extra 50 (25 invasive BC and 25 DCIS) cases for validation was utilised. Two sections per case were used: one stained with haematoxylin and eosin (H&E) stain for histological review and one unstained for examination using DIC microscopy. Collagen fibre parameters including orientation angle, fibre alignment, fibre density, fibre width, fibre length and fibre straightness were measured. Collagen fibre density was higher in the stroma of invasive BC (161.68±11.2fibre/µm2) compared to DCIS (p<0.0001). The collagen fibres were thinner (13.78±1.08µm), straighter (0.96±0.006, on a scale of 0-1), more disorganised (95.07°±11.39°) and less aligned (0.20±0.09, on a 0-1 scale) in the invasive BC compared to DCIS (all p<0.0001). A model considering these features was developed that could distinguish between DCIS and invasive tumours with 94% accuracy. There were strong correlations between fibre characteristics and clinicopathological parameters in both groups. A statistically significant association between fibre characteristics and patients' outcomes (breast cancer specific survival, and recurrence free survival) was observed in the invasive group but not in DCIS. Although invasive BC and DCIS were both associated with stromal reaction, the structural features of collagen fibres were significantly different in the two disease stages. Analysis of the stroma fibre characteristics in the preoperative core biopsy specimen may help to differentiate pure DCIS from those associated with invasion.

Clinico-pathological association of BCL2 in invasive breast carcinoma: A study from tertiary care health centre in Northern India.

B-cell lymphoma 2 (Bcl-2) is an antiapoptotic protein and an important clinical breast cancer prognostic marker. The aim of this study was to evaluate the relationship between the BCL2 expression and clinico-pathological parameters in breast cancer. Present study is observational cross-sectional study of 100 biopsy proven cases of breast cancer, and cases with resection specimens were included. IHC analyses for ER, PR, Her2neu, Ki67 and Bcl2 were performed in each case. Bcl2 expression was seen in 52% cases. BCL2-positive expression was associated with lower histological grade (0.026), low Ki-67 level (<14%, P < 0.001), hormone receptor positivity (P < 0.001) and luminal breast cancer (P < 0.001) but no association with tumour size, lymphovascular invasion, perineural invasion and TNM stage. Expression of Bcl-2, an antiapoptotic protein, is associated with low-grade, slowly proliferating, luminal A-type BC. IHC analysis of Bcl-2 is simple, inexpensive, readily available test to stratify early-stage hormone-positive patients who can be included in clinical trials for Bcl-2 inhibitors.

Shear-wave elastography as a supplementary tool for axillary staging in patients undergoing breast cancer diagnosis

BackgroundPreoperative evaluation of axillary lymph node status is crucial for the selection of both systemic and surgical treatment in early breast cancer. This study assessed the particular role of additional shear wave elastography (SWE) in axillary staging in patients undergoing initial breast cancer diagnostics.MethodsOne hundred patients undergoing axillary lymph node biopsy due to a sonographically suspicious axillary lymph node were prospectively evaluated with SWE using virtual touch tissue imaging quantification (VTIQ). Mean values of tissue stiffness for axillary tissue and lymph node tissue were measured prior to core-cut biopsy of the lymph node. All lymph nodes were clip-marked during the biopsy. Cut-off values to differentiate between malignant and benign lymph nodes were defined using Youden’s index.ResultsLymph nodes with evidence of malignant tumor cells in the final pathological examination showed a significantly higher velocity as measured by SWE, with a mean velocity of 3.48 ± 1.58 m/s compared to 2.33 ± 0.62 m/s of benign lymph nodes (p < 0.0001). The statistically optimal cutoff to differentiate between malignant and benign lymph nodes was 2.66 m/s with a sensitivity of 69.8% and a specificity of 87.5%.ConclusionsLymph node metastases assessed with SWE showed significantly higher elasticity values compared to benign lymph nodes. Thus, SWE provides an additional useful and quantifiable parameter for the sonographic assessment of suspicious axillary lymph nodes in the context of pre-therapeutic axillary staging in order to differentiate between benign and metastatic processes and support the guidance of definitive biopsy work-up.Critical relevance statementShear-wave elastography provides an additional useful and quantifiable parameter for the assessment of suspicious axillary lymph nodes in the context of pre-therapeutic axillary staging in order to differentiate between benign and metastatic processes and support guiding the definitive biopsy work-up.Key PointsSWE is a quantifiable ultrasound parameter in breast cancer diagnosis.SWE shows a significantly higher velocity in malignant lymph nodes.SWE is useful in improving the sensitivity and specificity of axillary staging.Graphical

Immunohistochemical Expression of Cyclooxygenase 2 (COX-2) as a Prognostic Marker and Its Correlation With Clinicopathological Parameters in Breast Cancer.

Introduction Breast cancer is considered the most common cancer among women. According to the literature, cyclooxygenase-2 (COX-2) expression in breast carcinoma is associated with aggressive tumor biology and acts as an independent prognostic marker. As COX-2 is a newly identified marker, studies are required to understand its immunoexpression and correlation with hormone receptor status and other prognostic factors, which helps in the therapeutic management of patients. Hence, this study evaluates the expression of COX-2 in breast carcinoma. Methods A hospital-based cross-sectional study was done on 55 mastectomy specimens collected at the Histopathology and Surgical Pathology Section of the Department of Pathology. The patient's age, histological type, tumor size, lymph node status, histological grade, and vascular invasion were noted. Immunohistochemical staining for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2/neu protooncogene (HER2/neu), and COX-2 markers was performed, and its results were compared with these clinicopathological and prognostic parameters. Results were subjected to statistical analysis. Results COX-2 expression was seen in 37 out of 55 cases (67.2%). Expression of COX-2 showed a statistically significant correlation with vascular invasion, ER-negative status, and PR-negative status. No statistical association was found between other parameters like age, tumor size, histological type, histological grade, lymph node status, and HER2/neu status. Conclusion The expression of COX-2 correlated strongly with well-established poor prognostic markers, such as vascular invasion, ER-negative status, and PR-negative status. Thus, expression of COX-2 suggests aggressive tumor biology, and it can be used as an independent prognostic marker.

Features of the expression of the transcription factor NF-kB in patients with secondary edematous breast cancer with various pro-inflammatory cytokines

Background. One of the most prominent features of secondary edematous breast cancer (SEBC), which is the most malignant form of this type of cancer, is severity of chronic inflammation that is important for pathogenesis and progression of the disease. As of now, there is evidence of association of carcinogenesis and inflammation. The transcription factor (NF-kB) and pro-inflammatory cytokines play a pivotal role in both inflammation and carcinogenesis. The regulation of NF-kB signal pathways is impaired in a lot of malignant diseases, including breast cancer (BC). Thus, the study of the content of pro-inflammatory cytokines and NF-kB is of high priority, as it can provide valuable information about the course of the tumor process. However, there are few research papers that deal with association of cytokine profile and NF-kB in breast tumors. Purpose – is to study the content of NF-kB-р105 and pro-inflammatory cytokines (IL-6, IL-8, TNFα) in the blood serum of patients with secondary edematous breast cancer. Materials and Methods. 87 patients (42 with SEBC, 45 with BC) were examined prior to treatment. The age of 42 patients with T4bN0-3M0 SEBC ranged from 34 to 71 years (median 53.1). The ductal cancer was found in 30 patients (71.43%), the lobular cancer – in 12 patients (28.57%). The tumor of more than 5 cm was detected in 20 individuals (47.6%), the tumor of less than 5 cm – in 22 individuals (52.4%). The comparison group consisted of 45 patients with BC, with their age ranging from 30 to 67 years (median 52.3). They had T3-4N1-3M0 non-edematous locally advanced BC. The tumor of more than 5 cm was detected in 12 patients (26.7%), the tumor of less than 5 cm – in 33 patients (73.3%). The ductal cancer was diagnosed in 33 patients (73.3%), the lobular cancer – in 12 patients (26.7%). The control group consisted of 10 patients with fibroadenomas. The content of cytokines (IL-1B, IL-2, IL-6, IL-8, TNFα) in the blood serum of patients was measured using the ELISA assay and CJSC «Vektor-Best» standard assay kits. The content of NF-kB1 subunit (р105 → р50) was measured using the ELISA assay and the Human NFkB – p105 (Nuclear factor NF-kappa-B p 105 subunit) ELISA Kit. The measurement was performed using the Immunochem-2100 American semi-automatic immunoassay analyzer. Results. It was found that in SEBC, the levels of pro-inflammatory cytokines IL-6, IL-8, TNFα were increased by 1.4 times, compared to the parameters in BC, and the level of IL-8 was the highest. The total level of NF-kB increased by 14,7 times in patients with SEBC and by 2,4 times in patients with BC, compared to individuals with fibroadenomas. The level of NF-kB in SEBC in groups with IL-6, TNFα was higher than in groups with BC by 3.1 and 1,7 times, respectively. It was found that the highest level of NF-kB was in the group with cytokine IL-8. In SEBC, it was higher by 5.7 times than in BC. In patients with SEBC, correlations between NF-kB and cytokines were established: NF-kB and IL-8 (r = 0.80; p &lt; 0.05); NF-kB and IL-6 (r = 0.60; p &lt; 0.05); NF-kB and TNFα (r = 0.60; p &lt; 0.05). Thus, one feature of SEBC is the increase in the content of NF-kB, IL-6, and TNFα, and also a significant increase in the level of NF-kB and IL-8, compared to the parameters in patients with BC as well as in patients with fibroadenomas. Conclusions. It was found that there was activation of the transcription factor NF-kB-p105 and a significant increase in the levels of pro-inflammatory cytokines (IL-6, IL-8, TNFα) in the blood serum of patients with SEBC, compared to patients with fibroadenomas, which indicates high carcinogenic potential of the tumor and the presence of the inflammatory component. It was demonstrated that the highest level of NF-kB-p105 was detected in the group of patients with SEBC with the highest level of cytokines IL-8. It was also found that in patients with SEBC, the level of the transcription factor and pro-inflammatory cytokines IL-6, IL-8, TNFα in the blood serum was significantly higher than in patients with BC, thereby confirming severe aggressiveness of this form of the disease.

Canonical Kaiso target genes define a functional signature that associates with breast cancer survival and the invasive lobular carcinoma histological type.

Invasive lobular carcinoma (ILC) is a low- to intermediate-grade histological breast cancer type caused by mutational inactivation of E-cadherin function, resulting in the acquisition of anchorage independence (anoikis resistance). Most ILC cases express estrogen receptors, but options are limited in relapsed endocrine-refractory disease as ILC tends to be less responsive to standard chemotherapy. Moreover, ILC can relapse after >15 years, an event that currently cannot be predicted. E-cadherin inactivation leads to p120-catenin-dependent relief of the transcriptional repressor Kaiso (ZBTB33) and activation of canonical Kaiso target genes. Here, we examined whether an anchorage-independent and ILC-specific transcriptional program correlated with clinical parameters in breast cancer. Based on the presence of a canonical Kaiso-binding consensus sequence (cKBS) in the promoters of genes that are upregulated under anchorage-independent conditions, we defined an ILC-specific anoikis resistance transcriptome (ART). Converting the ART genes into human orthologs and adding published Kaiso target genes resulted in the Kaiso-specific ART (KART) 33-gene signature, used subsequently to study correlations with histological and clinical variables in primary breast cancer. Using publicly available data for ERPOS Her2NEG breast cancer, we found that expression of KART was positively associated with the histological ILC breast cancer type (p < 2.7E-07). KART expression associated with younger patients in all invasive breast cancers and smaller tumors in invasive ductal carcinoma of no special type (IDC-NST) (<2 cm, p < 6.3E-10). We observed associations with favorable long-term prognosis in both ILC (hazard ratio [HR] = 0.51, 95% CI = 0.29-0.91, p < 3.4E-02) and IDC-NST (HR = 0.79, 95% CI = 0.66-0.93, p < 1.2E-04). Our analysis thus defines a new mRNA expression signature for human breast cancer based on canonical Kaiso target genes that are upregulated in E-cadherin deficient ILC. The KART signature may enable a deeper understanding of ILC biology and etiology. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Correlation between standardized uptake value of 18F-FDG PET/CT and conductivity with pathologic prognostic factors in breast cancer

We investigated the correlation between standardized uptake value (SUV) of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) and conductivity parameters in breast cancer and explored the feasibility of conductivity as an imaging biomarker. Both SUV and conductivity have the potential to reflect the tumors’ heterogeneous characteristics, but their correlations have not been investigated until now. Forty four women diagnosed with breast cancer who underwent breast MRI and 18F-FDG PET/CT at the time of diagnosis were included. Among them, 17 women received neoadjuvant chemotherapy followed by surgery and 27 women underwent upfront surgery. For conductivity parameters, maximum and mean values of the tumor region-of-interests were examined. For SUV parameters, SUVmax, SUVmean, and SUVpeak of the tumor region-of-interests were examined. Correlations between conductivity and SUV were evaluated, and among them, the highest correlation was observed between mean conductivity and SUVpeak (Spearman’s correlation coefficient = 0.381). In a subgroup analysis for 27 women with upfront surgery, tumors with lymphovascular invasion (LVI) showed higher mean conductivity than those without LVI (median: 0.49 S/m vs 0.06 S/m, p < 0.001). In conclusion, our study shows a low positive correlation between SUVpeak and mean conductivity in breast cancer. Furthermore, conductivity showed a potential to noninvasively predict LVI status.

A degradome-based prognostic signature that correlates with immune infiltration and tumor mutation burden in breast cancer.

Female breast cancer is the most common malignancy worldwide, with a high disease burden. The degradome is the most abundant class of cellular enzymes that play an essential role in regulating cellular activity. Dysregulation of the degradome may disrupt cellular homeostasis and trigger carcinogenesis. Thus we attempted to understand the prognostic role of degradome in breast cancer by means of establishing a prognostic signature based on degradome-related genes (DRGs) and assessed its clinical utility in multiple dimensions. A total of 625 DRGs were obtained for analysis. Transcriptome data and clinical information of patients with breast cancer from TCGA-BRCA, METABRIC and GSE96058 were collected. NetworkAnalyst and cBioPortal were also utilized for analysis. LASSO regression analysis was employed to construct the degradome signature. Investigations of the degradome signature concerning clinical association, functional characterization, mutation landscape, immune infiltration, immune checkpoint expression and drug priority were orchestrated. Cell phenotype assays including colony formation, CCK8, transwell and wound healing were conducted in MCF-7 and MDA-MB-435S breast cancer cell lines, respectively. A 10-gene signature was developed and verified as an independent prognostic predictor combined with other clinicopathological parameters in breast cancer. The prognostic nomogram based on risk score (calculated based on the degradome signature) showed favourable capability in survival prediction and advantage in clinical benefit. High risk scores were associated with a higher degree of clinicopathological events (T4 stage and HER2-positive) and mutation frequency. Regulation of toll-like receptors and several cell cycle promoting activities were upregulated in the high-risk group. PIK3CA and TP53 mutations were dominant in the low- and high-risk groups, respectively. A significantly positive correlation was observed between the risk score and tumor mutation burden. The infiltration levels of immune cells and the expressions of immune checkpoints were significantly influenced by the risk score. Additionally, the degradome signature adequately predicted the survival of patients undergoing endocrinotherapy or radiotherapy. Patients in the low-risk group may achieve complete response after the first round of chemotherapy with cyclophosphamide and docetaxel, whereas patients in the high-risk group may benefit from 5-flfluorouracil. Several regulators of the PI3K/AKT/mTOR signaling pathway and the CDK family/PARP family were identified as potential molecular targets in the low- and high-risk groups, respectively. In vitro experiments further revealed that the knockdown of ABHD12 and USP41 significantly inhibit the proliferation, invasion and migration of breast cancer cells. Multidimensional evaluation verified the clinical utility of the degradome signature in predicting prognosis, risk stratification and guiding treatment for patients with breast cancer.

Evaluation oncotype DX® 21-gene recurrence score andclinicopathological parameters: a single institutional experience.

Oncotype DX recurrence score (RS) is a clinically validated assay, which predicts the likelihood of disease recurrence in oestrogen receptor-positive/HER2-negative (ER+/HER2-) breast cancer (BC). In this study we aimed to compare the performance of Oncotype DX against the conventional clinicopathological parameters using a large BC cohort diagnosed in a single institution. A cohort (n= 430) of ER+/HER2- BC patients who were diagnosed at the Nottingham University Hospitals NHS Trust and had Oncotype DX testing was included. Correlation with the clinicopathological and other biomarkers, including the proliferation index, was analysed. The median Oncotype DX RS was 17.5 (range=0-69). There was a significant association between high RS and grade 3 tumours. No grade 1BC or grade 2 tumours with mitosis score 1 showed high RS. Low RS was significantly associated with special tumour types where none of the patients with classical lobular or tubular carcinomas had a high RS. There was an inverse association between RS and levels of ER and progesterone receptor (PR) expression and a positive linear correlation with Ki67 labelling index. Notably, six patients who developed recurrence had an intermediate RS; however, four of these six cases (67%) were identified as high-risk disease when the conventional clinical and molecular parameters were considered. Oncotype DX RS is correlated strongly with the conventional clinicopathological parameters in BC. Some tumour features such as tumour grade, type, PR status and Ki67 index can be used as surrogate markers in certain scenarios.

EFFECTIVENESS OF ALPHA-LIPOIC ACID AND IPIDACRINE HYDROCHLORIDE IN PREVENTION OF PACLITAXEL-INDUCED PERIPHERAL NEUROPATHY ASSESSED BY ELECTRONEUROMYOGRAPHY OF SUPERFICIAL PERONEAL AND SURAL NERVES.

To investigate theneurofunctional parameters in breast cancer (BC) patients with paclitaxel-induced peripheral neuropathy(PIPN) and to clarify thefeasibility of using alpha-lipoic acid (ALA) in combination with theacetylcholinesterase inhibitor ipidacrine hydrochloride (IPD) for its prevention. 100BC patients (T1-4N0-3M0-1) prescribed for polychemotherapy (PCT) by theAT (paclitaxel, doxorubicin) or ET (paclitaxel, epirubicin) regimens in theneoadjuvant, adjuvant or palliative modes, were enrolled. Thepatients were randomized into two groups (n = 50per group): group I treated by PCT only; group II treated with PCT plus thestudied PIPN prevention scheme (ALA in combination with IPD). An electroneuromyography (ENMG) of thesensory (superficial peroneal and sural) nerves was performed before PCT, and after the3and 6PCT cycles. According to ENMG data, theelectrophysiological disturbances in thesensory nerves were manifested in theform of axonal sensory peripheral neuropathy of a symmetrical nature, which was reflected in a decrease in theamplitude of theaction potential (AP) of thestudied nerves. TheAP reduction in sensory nerves was dominant, in contrast to thenerve conduction velocity, which in most patients remained within thereference values, thus evidencing on axonal degeneration rather than demyelination as an underlying cause of PIPN. TheENMG testing of thesensory nerve in thegroups of BC patients treated by PCT with paclitaxel with or without PIPN prevention treatment established that theuse of ALA in combination with IPD significantly improved AP amplitude, duration and area of ​​theresponse to thestimulation of thesuperficial peroneal and sural nerves after 3and 6PCT cycles. Theuse of ALA in combination with IPD significantly reduced theseverity of damage to thesuperficial peroneal and sural nerves caused by PCT with paclitaxel and could be recommended for PIPN prevention.

P16 Expression in Human Breast Carcinoma and its Relationship to Clinicopathological Parameters.

p16 is a cyclin-dependent kinase inhibitor and a cardinal regulator of the cell cycle. The relationship between p16 overexpression and poor prognosis of breast cancer has been reported in some studies. This study aimed to evaluate p16 expression in breast cancer in comparison to normal breast tissue and determine the association between p16 expression and clinicopathological parameters in breast cancer. Paraffin blocks of 110 samples were studied. These included 40 invasive breast carcinoma (tumor group) and normal tissue adjacent to the tumor (tumor control), as well as 30 normal mammoplasty specimens (normal control). Samples were from the pathology archive of Alzahra Hospital, Isfahan, Iran, from 2016 to 2020. p16 expression was studied and compared in these three groups using the immunohistochemistry technique. Moreover, the relationship between p16 expression and age, tumor size, carcinoma subtype, tumor grade, and lymph node involvement was investigated in the tumor group. SPSS version 16 was used to analyze data. p16 expression showed a significant difference between the tumor group and the two control groups with a significantly higher expression in the tumor group. There was a significant direct relationship between the intensity of p16 expression and the number of involved lymph nodes (P < 0.001). No significant relationship was detected between p16 expression and other clinicopathological factors. p16 seems to have a rather significant expression in breast cancer in comparison to normal breast parenchyma. However, among clinicopathological parameters, we found only a direct relationship between lymph node involvement and intensity of p16 expression.

CD47 expression and tumor-associated immune cells in breast cancer and their correlation with molecular subtypes and prognostic factors.

Breast cancer is the most common malignancy in women and a heterogeneous disease at the molecular level. Since most breast cancer cases are not of a special type, it is suggested that tumor-associated macrophages and tumor-infiltrating lymphocytes, which are involved in tumor growth, invasion, angiogenesis, and metastasis, may be important factors that should be evaluated together with standard criteria to determine the prognosis of cancer and assist in treatment decisions and outcome stratification. In this study, CD47 expression, which is involved in macrophage-mediated immune escape, tumor-infiltrating lymphocytes, and tumor-associated macrophages were evaluated in breast cancer molecular subgroups and correlated with prognostic factors. The immunohistochemistry of CD47, CD163, and CD3 was analyzed on the tissue microarrays of 278 invasive breast cancer cases. The CD47, CD163, and CD3 expressions were found to be correlated with various clinicopathological parameters in breast cancer. High levels of CD47, CD163, and CD3 expressions had a significant correlation with the ER status and PR status, Ki-67 proliferation index, and molecular subtype (P<0.05). The CD47 expression had a significant correlation with the CD3 and CD163 expressions (p=0.021 and p=0.001, respectively). Our results suggest that CD47, CD163, and CD3 may be among the prognostic factors of breast cancer. The combined use of CD47, CD163, and CD3 can be a new prognostic factor for patients with breast cancer, especially as a therapeutic target in hormone receptor-negative breast cancer cases and those with a high proliferation index.

Estrogen Receptor Alpha Gene Amplification Is an Independent Predictor of Long-Term Outcome in Postmenopausal Patients with Endocrine-Responsive Early Breast Cancer.

Estrogen receptor (ER) expression is a prognostic parameter in breast cancer, and a prerequisite for the use of endocrine therapy. In ER+ early breast cancer, however, no receptor-associated biomarker exists that identifies patients with a particularly favorable outcome. We have investigated the value of ESR1 amplification in predicting the long-term clinical outcome in tamoxifen-treated postmenopausal women with endocrine-responsive breast cancer. 394 patients who had been randomized into the tamoxifen-only arm of the prospective randomized ABCSG-06 trial of adjuvant endocrine therapy with available formalin-fixed, paraffin-embedded tumor tissue were included in this analysis. IHC ERα expression was evaluated both locally and in a central lab using the Allred score, while ESR1 gene amplification was evaluated by FISH analysis using the ESR1/CEP6 ratio indicating focal copy number alterations. Focal ESR1 copy-number elevations (amplifications) were detected in 187 of 394 (47%) tumor specimens, and were associated with a favorable outcome: After a median follow-up of 10 years, women with intratumoral focal ESR1 amplification had a significantly longer distant recurrence-free survival [adjusted HR, 0.48; 95% confidence interval (CI), 0.26-0.91; P = 0.02] and breast cancer-specific survival (adjusted HR 0.47; 95% CI, 0.27-0.80; P = 0.01) as compared with women without ESR1 amplification. IHC ERα protein expression, evaluated by Allred score, correlated significantly with focal ESR1 amplification (P < 0.0001; χ2 test), but was not prognostic by itself. Focal ESR1 amplification is an independent and powerful predictor for long-term distant recurrence-free and breast cancer-specific survival in postmenopausal women with endocrine-responsive early-stage breast cancer who received tamoxifen for 5 years.

Predicting axillary lymph node metastasis in breast cancer using the similarity of quantitative dual-energy CT parameters between the primary lesion and axillary lymph node

PurposeTo evaluate the similarity of quantitative dual-energy computed tomography (DECT) parameters between the primary breast cancer lesion and axillary lymph node (LN) for predicting LN metastasis.Materials and methodsThis retrospective study included patients with breast cancer who underwent contrast-enhanced DECT between July 2019 and April 2021. Relationships between LN metastasis and simple DECT parameters, similarity of DECT parameters, and pathological and morphological features were analyzed. ROC curve analysis was used to evaluate diagnostic ability.ResultsOverall, 137 LNs (39 metastases and 98 non-metastases) were evaluated. Significant differences were observed in some pathological (nuclear grade, estrogen receptor status, and Ki67 index) and morphological characteristics (shortest and longest diameters of the LN, longest-to-shortest diameter ratio, and hilum), most simple DECT parameters, and all DECT similarity parameters between the LN metastasis and non-metastasis groups (all, P < 0.001–0.004). The shortest diameter of the LN (odds ratio 2.22; 95% confidence interval 1.47, 3.35; P < 0.001) and the similarity parameter of 40-keV attenuation (odds ratio, 2.00; 95% confidence interval 1.13, 3.53; P = 0.017) were independently associated with LN metastasis compared to simple DECT parameters of 40-keV attenuation (odds ratio 1.01; 95% confidence interval 0.99, 1.03; P =0.35). The AUC value of the similarity parameters for predicting metastatic LN was 0.78–0.81, even in cohorts with small LNs (shortest diameter < 5 mm) (AUC value 0.73–0.78).ConclusionThe similarity of the delayed-phase DECT parameters could be a more useful tool for predicting LN metastasis than simple DECT parameters in breast cancer, regardless of LN size.

Relationship of Nottingham Prognostic Index with prognostic parameters of breast carcinoma

Background: Breast cancer (BC) is the commonest malignancy in the female and it is gaining its significance due to worldwide rising incidence. It is also important due to 2.5% higher incidence in Pakistan as compared to neighbouring countries. Nottingham prognostic index (NPI) is an important prognostic factor of BC. It provides information about survival and morbidity. There are significant variations in different studies. Aim: To carry out current study relating NPI with various histopathological parameters of BC. Methods: This was a descriptive cross-sectional study. The study was done at the Department of Pathology, King Edward Medical University Lahore with the collaboration of four surgical units of Mayo Hospital Lahore from 2010 to 2019. Total 137 cases of breast carcinoma were included. Information about age, grade, primary tumor size, axillary lymph node status and stage was entered in the pre designed proforma. NPI was calculated as 0.2xtumor size(cm)+lymph node grade. NPI was scored as excellent, good, moderate and poor and its correlation was calculated against primary tumor size, lymph node grade, tumor grade and stage. Results: We studied 137 cases of breast carcinoma with mean age 49.32±11.64 years. Mean NPI was 5.4±1.4 with range of 2.4 to 9.4. NPI scores in poor 65(47.4%) and moderate 61(44.5%) groups were significantly high as compared to good 10(7.3%) and excellent scores 1(0.7%). Most of the cases of poor NPI were in p T3 and p T4 whereas this was p T2 with moderate score. Poor score of NPI was significant in grade 3 which is in contrast to moderate score where grade 2 dominated the picture. Correlation of NPI with LNG was in favor of LNG 1 with good and moderate scores while LNG3 dominated in the poor group. In stage III, 49 cases (35.8%) were seen with poor score of NPI. Conclusion: NPI is an important prognostic parameter and it can be studied with different histopathological parameters to see correlation between them. In the current study majority of the cases of NPI scored at poor and moderate levels. Correlation coefficient was linear, strong and positive especially with LNG. Mean NPI has ascending correlation with these parameters. Thus NPI can be used as a prognostic indicator when comparing with histopathological parameters of BC. Keywords: Breast cancer, NPI, tumor grade, tumor stage, LNG

Assessing the interrelation between oestrogen receptor status, heart rate variability and serum nitric oxide in breast cancer patients: Understanding their prognostic relevance.

e12564 Background: Heart Rate Variability (HRV) is a non-invasive procedure to assess cardiac functions and provides an index of autonomic function that intricately controls vascular tone. Studying the alteration in HRV with agents producing oxidative stress will provide useful information about disease progression. Lower HRV indicates low level of Parasympathetic Nervous System activation and dysregulation of cardiac functions. Elements of tumour microenvironment like prostaglandin E2, oestrogen and hypoxia stimulate nitric oxide (NO) production which reacts with free radicals released by tumour tissue forming oxidising agents. NO enhances oxidative stress causing vascular dysfunction. Very few studies have reported an interrelationship between NO and HRV parameters in breast cancer. The aim of the study is to verify the relation between HRV and serum NO levels in ER+ and ER- breast cancer groups. Methods: Study design: Analytical, Cross sectional. Sample Size: 135 women above 20 years of age with and without breast cancer. 69 women with histologically proven breast cancer in different stages and 66 women who were healthy age matched controls were included. Oestrogen Receptor (ER) status was obtained from clinical records. Out of 69 women with breast cancer, 31 were ER- with 15 in stage 1 and 16 in stage 2. 38 women were ER+ with 5 in stage 2 and 33 in stage 3. Serum NO was measured using colorimetry. Heart Rate Variability was measured from lead II ECG using Power Lab 15T and lab chart software. Serum NO levels and HRV parameters were compared between ER groups. Results: ER+ women had higher HRV with parasympathetic predominance compared to ER- with p&lt;0.001. ER+ women also had higher serum NO levels compared to ER- group with p&lt;0.001. Though no direct correlation was noticed between NO and HRV, multiple analysis of variance showed significant (p&lt;0.001) difference of all values across the groups. irrespective of menopausal status. Conclusions: A significant difference was observed in HRV of ER+ and ER- women with breast cancer. Most ER+ women were in stage 3 with significantly higher NO levels. Serum NO is expected to be the factor most responsible for HRV changes particularly in stage 3/ER+. Parasympathetic predominance seen in ER+ women possibly is due to high NO levels.[Table: see text]

Clinical and morphological features of breast tumors with PIK3CA mutations in Russian patients: Observational study

Background. By 2020, breast cancer (BC) has become the most frequent malignancy in the world. The most common type of BC is HR+/HER2-negative cancer,2540% of which harbors PIK3CA mutations that affect the catalytic subunit of the PI3K protein. PIK3CA alterations are actionable, as such neoplasms can be treated with a combination of fulvestrant and the PI3K inhibitor alpelisib. As PIK3CA mutations have an extremely versatile effect on the characteristics of a tumor cell, numerous associations of PIK3CA mutations and various clinico-pathological characteristics of BC can be traced.&#x0D; Aim. Our aim was to clarify the information on the frequency and spectrum of PIK3CA mutations in Russian patients with HR+/HER2- advanced BC, and to study the association of PIK3CA mutations with clinical and pathological parameters of BC.&#x0D; Materials and methods. Tissue samples from 694 patients with HR+/HER2- advanced BC (mixed population of primary metastatic and relapsed tumors) who received any line of anti-cancer treatment in Dec 2020 to June 2021 in Russian Federation were analyzed by high-resolution melting, allele-specific PCR, digital droplet PCR and Sanger sequencing (exons 7,9, and 20 of the PIK3CA gene). Mutation rates in different BC subgroups were compared using the Fishers exact test. The age at diagnosis in patients with different PIK3CA status was compared using the MannWhitney U-test. The relationship between the PIK3CA status and the degree of tumor differentiation was compared using the CochraneArmitage test for trends. Luminal A and B BC expression subtypes were distinguished with surrogate IHC markers according to St.-Gallen recommendations (2013).&#x0D; Results. Mutations were identified in 220/694 (32%) BC patients. The three most frequent missense substitutions in the PIK3CA gene (p.E542K, p.E545K, and p.H1047R) accounted for 190/220 (86%) mutations. Associations of PIK3CA mutations with luminal A subtype of BC, low proliferation index, small size of the primary tumor, and absence of signs of hereditary cancer were revealed. Associations of mutations in the kinase domain of PIK3CA (p.H1047R) with late recurrence of locally advanced BC and with non-Slavic ethnic origin of patients were found.&#x0D; Conclusion. PIK3CA mutation rate of 32% confirms high prevalence of mutation in Russian population, with some differences reflecting the ethnic origin of patients.

Evaluation of Immunohistochemical Expression of Topoisomerase II Alpha Protein in Patients with Breast Cancer and Its Correlation with Different Prognostic Factors

Background: There are indications to support the knowledge about the prognosis of breast cancer. One of these markers is regarded as a prognostic factor and related to the proliferation rate. Topoisomerase IIα (TOP2A), encoded by the TOP2A gene, is a molecular target for anthracycline therapy. Aims: The aim of this article is to establish any association of the status of topoisomerase IIa immunohistochemistry with different prognostic clinicopathological and molecular parameters in breast cancer. Settings and Design: A cross-sectional retrospective study was carried out in the Department of Pathology and Forensic Medicine, Faculty of Medicine, Babylon University, during the period from January 2020 through December 2020. Materials and Methods: Fifty cases with invasive breast carcinoma have been obtained from surgical modified radical mastectomy specimens from the Laboratory of Histopathology in Al-Kafeel Specialized Hospital, Karbala for the last 3 years (2017–2019). Different clinicopathological variables were estimated. The expression of TOP2A was stained by using the PathnSitu PolyExcel Detection System of Immunostaining. Statistical Analysis Used: Immunostaining with TOP2A expression used a cut-off value of 10%. The results were considered statistically significant if the P-value was ≤ 0.05. Results: Fifty cases of TOP2A overexpression were classified as follows: 28 cases (56%) had 3+ expression, 4 cases (8%) with 2+ expression, and 4 cases (8%) with 1+ expression, whereas 14 cases had no expression of TOP2A (28%). TOP2A overexpression was shown to be associated with a higher grade (P = 0.023) and molecular subtypes (P = 0.057), but not with other clinicopathological parameters (age of patients, type of histology, number of lymph nodes involved, tumor size). Conclusion: According to these results, TOP2A plays a major role in the aggressive nature of tumors. This may support the suggestion to be used as a prognosis marker.

Role of peripheral blood parameters (neutrophil-to-lymphocyte, lymphocyte-to-monocyte and neutrophil-to-monocyte ratios) in breast cancer

Background: Nowadays, the role of inflammation in malignancies is well understood, and it has been characterised at several phases of tumourigenesis (initiation, promotion, invasion and metastasis). Different studies suggested that the neutrophils/lymphocyte ratio (NLR) is linked with breast cancer (BC) survival and prognosis. Aim: In the present study, our aim was to study the blood parameters (neutrophils, lymphocytes, NLR, lymphocyte-to-monocyte ratio [LMR] and neutrophil-to-monocyte ratio [NMR]) in BC. We examined the correlation between white blood cells, NLR, LMR, NMR and BC. Materials and Methods: It was a case–control study, which included 97 individuals, in which 44 were confirmed BC patients by histopathological examination and 53 were healthy controls. Their personal and social status information were collected in questionnaire form. Results: The mean neutrophil count was higher in the case group as compared to the control group (65.45 ± 5.92/68.67 ± 9.13, P = 0.001). Lymphocyte count was significantly lower in the case group as compared to the control group (26.25 ± 8.78 vs. 29.79 ± 5.14, P = 0.00). NLR was higher in the case group as compared to the control group, 3.03 ± 1.36 versus 2.35 ± 1.02, P = 0.00. The monocyte level was significantly higher in BC patients as compared to the control group, i.e. 2.80 ± 0.79 versus 2.66 ± 1.07, P = 0.01, in the case group. The LMR was 13.55 ± 7.21 in the control group and 10.35 ± 5.57, P = 0177, in the case group. NMR was significantly higher in the control group as compared to the case group (30.42 ± 17.02 vs. 26.53 ± 8.50, P = 0.002). Conclusions: Low NMR value can be related to a greater survival rate. We concluded that complete blood count, NLR and NMR can be an alternative marker in BC risk.

Topographical distribution and histological characterization of stromal fibrosis in invasive breast carcinoma

Carcinoma breast is associated with various changes in organ and at the tissue level. The desmoplastic response in a tumor due to tumor hypoxia may result in dense or sparse, homogenous or focally hetrogenous fibrosis of the breast tissue. Peritumoral and stromal fibrosis has been assessed as an marker of intratumoral hypoxia and is being studied as histological surrogate prognostic parameter in breast cancer. We studied the topographical distribution and histological characterization of fibrosis and correlated it with various other histopathological parameters. 50 patients of carcinoma breast presenting to our institute were included in the study. We obtained a statistically significant correlation of presence of fibrosis with presence of lymphovascular invasion (p value =0.043), while we could not obtain any significant difference with age, menopause, tumor size, tumor grade, pathological stage, lymph node involvement, presence of necrosis, adipocytic invasion, duration of tumor, laterality, presence of inflammatory infiltrate and with ER, PR, HER2Neu status. This is a limited study in a small number of patients focussing on various stromal changes in breast cancer. This study has further characterized the heterogeneous nature of fibrosis in breast carcinoma using special staining which may facilitate the physician in making patient diagnosis, prognostication and outcome.