scholarly journals Activated Leukocyte Cell Adhesion Molecule (ALCAM) in Saudi Breast Cancer Patients as Prognostic and Predictive Indicator

2015 ◽  
Vol 9 ◽  
pp. BCBCR.S25563 ◽  
Author(s):  
Fawziah S. Al-Shehri ◽  
Eman M. Abd EL Azeem

Background Activated leukocyte cell adhesion molecules (ALCAMs) play an essential role in tumor metastasis and are higher in some patients with breast cancer. AIM This study aimed to evaluate ALCAM as an early diagnostic biomarker for breast cancer and how it compares with other markers. Subjects and Methods One-hundred and sixty-one women were selected for this study. They were divided into three groups: Group 1 consisted of 42 healthy individuals (control) while a patients groups divided into two groups according to tumour grade, Group II, Include 58 breast cancer patient's grade II and Group III, Include 61 patients with grade III of breast cancer. Tumour markers CEA, CA 15–3 and s ALCAM levels were determined and Group 2 consisted of breast cancer patients. Results A highly significant elevation was recorded in s ALCAM, CA 15–3 and CEA. Percent change for grade II and grade III were [sALCAM (90, 127)], [CA15–3 (40, 72)] and [CEA (33, 156)]. Operating characteristic (ROC) curves were used to evaluate the diagnostic performance of the biomarkers ALCAM, CA15–3 and CEA with area under the curve (AUC) of (0.99 & 1.0) (AUC 0.947 & 0.99) and (AUC 0.88 & 0.94) for grade II and grade III respectively the incremental values of AUC were statistically highly significant (p < 0.001). Conclusion It could be concluded that serum ALCAM concentration represents a suitable biomarker for Saudi arabian breast carcinoma with high sensitivity and has the potential to be used as a diagnostic tool comparable to CA15–3 and CEA.

2021 ◽  
Author(s):  
Kaiwen Shen ◽  
Longdi Yao ◽  
Huihua Cao ◽  
Ximing Gu ◽  
Jie Wang ◽  
...  

Abstract Background There is no definitive, unified view on chemotherapy for T1 pN0M0 breast cancer. Our study explored the effects of chemotherapy on T1 pN0M0 breast cancer. Methods 75,139 patients diagnosed with T1 pN0M0 breast cancer were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Multivariate Cox analyses were performed to investigate the effects of chemotherapy on T1a, T1b, and T1c pN0M0 breast cancer, various tumor grades, and four molecular subtypes. Propensity score matching (PSM) was used to eliminate confounding factors and further verify the results between chemotherapy and no chemotherapy. Finally, 545 T1pN0M0 breast cancer patients treated at the Northern Jiangsu People’s Hospital were included for external validation. Univariate and multivariate Cox analyses were used to confirm the role of chemotherapy in T1a, T1b, and T1c pN0M0 breast cancer. Survival curves were plotted using the Kaplan–Meier method for tumor grades and molecular subtypes. Results Chemotherapy demonstrated a statistically significant improvement in T1b and T1c breast cancer, not in T1a breast cancer. With T1b breast cancer, chemotherapy had effects on grade III and molecular subtypes hormone receptor+ [HR+]/human epidermal growth factor receptor 2+ [HER2+], HR-/HER2+, and HR-/HER2-. Chemotherapy was beneficial to overall survival for grade II/III and T1c breast cancer. After PSM, identical results were obtained. We also obtained similar results with external validation, except that chemotherapy made a difference in grade II and T1b breast cancer of external validation. Conclusion Partial T1 pN0M0 breast cancer patients with tumor grade III T1b pN0M0 except HR+/HER2-, those with tumor grade II and III T1c pN0M0 can obtain overall survival benefits from chemotherapy.


Author(s):  
Stefano Giannoni-Luza ◽  
Oscar Acosta Conchucos ◽  
Alexis Germán Murillo Carrasco ◽  
Pierina Danos ◽  
José Manuel Cotrina Concha ◽  
...  

PIK3CA is a gene usually mutated in breast cancer and has an important role in tumor progression and treatment. Therefore, there is required a technique to detect low-rate PIK3CA mutations improving the clinical conduct. This study aimed to compare chip-based dPCR and Sanger sequencing to detect PIK3CA mutations in breast cancer patients. Fifty-seven tumor samples from breast cancer patients were collected and analyzed by Sanger sequencing and dPCR for PIK3CA mutations (E545K, H1047R, and H1047L). Digital PCR sensitivity, specificity, and overall performance were estimated by contingency tables, receptor operator characteristic (ROC), and area under the curve (AUC). Sanger sequencing identified PIK3CA mutations in six patients (10.5%), two with H1047R, and four with E545K. Digital PCR confirmed those mutations and identified 19 additional patients with at least one mutation. Comparison between dPCR and Sanger sequencing showed a sensitivity of 100% (95% CI 53-100%), and a specificity of 84.2% (95% CI 83 - 84.2%). Besides, H1047R mutation showed a significant association with breast cancer phenotype (p =0.019) and lymphatic node infiltration (p =0.046). Digital PCR showed a high sensitivity to detect mutations in tumor samples and it might be capable to detect low-rate mutations and tumor subpopulations not detected by Sanger sequencing.


2018 ◽  
Vol 6 (4) ◽  
pp. 593-599 ◽  
Author(s):  
Magdalena Bogdanovska-Todorovska ◽  
Slavica Kostadinova-Kunovska ◽  
Rubens Jovanovik ◽  
Blagica Krsteska ◽  
Goran Kondov ◽  
...  

BACKGROUND: Accurate assessment of HER-2 is imperative in selecting patients for targeted therapy. Most commonly used test methods for HER-2 are immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH). We evaluated the concordance between FISH and IHC for HER-2 in breast cancer samples using Food and Drug Administration approved tests.MATERIAL AND METHODS: Archived paraffin tissue blocks from 73 breast cancer patients were used. HER-2 immunostaining was performed using Ventana anti–HER-2 monoclonal antibody. The FISH assay was performed using PathVysion™ HER-2 DNA Probe Kit.RESULTS: Of the 73 cases 68.5% were IHC 0/1+, 15.07% were IHC 2+ and 16.44% were IHC 3+. Successful hybridisation was achieved in 72 cases. HER-2 FISH amplification was determined in 16.67% cases. Ten IHC 3+ and two IHC 2+ cases were FISH positive. Two of the IHC 3+ cases were FISH negative. Concordance rate was 100%, 18.18% and 83.33% for IHC 0/1+, 2+ and 3+ group, respectively. Total concordance was 84.72%, kappa 0.598 (p < 0.0001). The sensitivity of IHC in detecting IHC 2+ and IHC 3+ cases was 16.7% and 83.3%, and the specificity was 85% and 96.67%, respectively.CONCLUSION: The consistency between the methods was highest for IHC negative and lowest for IHC equivocal cases. The immunohistochemistry showed high sensitivity for IHC 2+/3+ cases and high specificity for IHC 3+ cases. Our results support the view that false-positive rather than false-negative IHC results are a problem with HER-2/IHC testing, and that IHC should be used as an initial screening test, but IHC 2+/ 3+ results should be confirmed by FISH.


2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Xufei Liang ◽  
Yueying Wang ◽  
Xi Yin ◽  
Xiaohong Gong ◽  
Shuo Pan ◽  
...  

Introduction. Patients receiving chemotherapy for breast cancer may be at risk of developing cardiac dysfunction and electrophysiological abnormalities. The aim of this study is to evaluate alterations in electrocardiographic (ECG) parameters in breast cancer patients receiving chemotherapy. Materials and Methods. This was a prospective single-center cohort study conducted in the Fourth Hospital of Hebei Medical University, China. Participants with breast cancer referred for chemotherapy from May 1, 2019, to October 1, 2019, were invited to participate in the study. Standard 12-lead ECG and echocardiography were performed at baseline or before chemotherapy (prechemotherapy) (T0), after 1 cycle (T1), after 3 cycles (T2), and at the end of chemotherapy (T3). Results. A total of 64 patients with diagnosed breast cancer undergoing chemotherapy were included. Echocardiographic parameters showed no significant variation during the entire procedure (all P > 0.05 ). The incidence of abnormal ECG increased from 43.75% at baseline to 65.63% at the end of chemotherapy, of which only the prevalence of fragmented QRS (fQRS) was significantly increased after the drug regimen (26.56% to 53.13%). At the end of the treatment, heart rate, P-wave dispersion, corrected QT interval, T-peak to T-end, RR, SV1, RV5, Sokolow–Lyon index (SLI), and index of cardioelectrophysiological balance deteriorated markedly (all P < 0.05 ). The area under the curve for SLI and QT dispersion (QTd) derived by ECG was 0.710 and 0.606, respectively. The cutoff value with 2.12 of SLI by ECG had a sensitivity of 67.2% and specificity of 71.9% for differentiating patients after therapy from baselines. The cutoff value with 0.55 of QTd had a sensitivity of 60.9% and specificity of 60.9%. Conclusions. The current study demonstrated that ECGs can be used to detect electrophysiological abnormalities in breast cancer patients receiving chemotherapy. ECG changes can reflect subclinical cardiac dysfunction before the echocardiographic abnormalities.


2020 ◽  
Vol 28 (1) ◽  
pp. 382-400
Author(s):  
Wei Chong ◽  
Huikun Zhang ◽  
Zhifang Guo ◽  
Limin Yang ◽  
Ying Shao ◽  
...  

AbstractAnthracyclines are a class of conventional and commonly used frontline chemotherapy drugs to treat breast cancer. However, the anthracycline-based regimens can only reduce breast cancer mortality by 20–30%. Furthermore, there is no appropriate biomarker for predicting responses to this kind of chemotherapy currently. Here we report our findings that may fill this gap by showing the AQP1 (Aquaporin1) protein as a potential response predictor in the anthracycline chemotherapy. We showed that breast cancer patients with a high level of AQP1 expression who underwent the anthracycline treatment had a better clinical outcome relative to those with a low level of AQP1 expression. In the exploration of the underlying mechanisms, we found that the AQP1 and glycogen synthase kinase-3β (GSK3β) competitively interacted with the 12 armadillo repeats of β-catenin, followed by the inhibition of the β-catenin degradation that led to β-catenin’s accumulation in the cytoplasm and nuclear translocation. The nuclear β-catenin interacted with TopoIIα and enhanced TopoIIα’s activity, which resulted in a high sensitivity of breast cancer cells to anthracyclines. We also found, the miR-320a-3p can attenuate the anthracycline’s chemosensitivity by inhibiting the AQP1 expression. Taken together, our findings suggest the efficacy of AQP1 as a response predictor in the anthracycline chemotherapy. The application of our study includes, but is not limited to, facilitating screening of the most appropriate breast cancer patients (who have a high AQP1 expression) for better anthracycline chemotherapy and improved prognosis purposes.


2019 ◽  
Vol 18 ◽  
pp. 153303381982870 ◽  
Author(s):  
Bin Shao ◽  
Xiaoxia Wang ◽  
Lei Zhang ◽  
Deyu Li ◽  
Xiaoran Liu ◽  
...  

Background: MicroRNAs contribute to chemotherapy response in different types of cancer. We hypothesized that plasma miRNAs are potentially associated with chemotherapy response in patients with metastatic breast cancer. Patients and Methods: Fourteen candidate microRNAs were chosen from the literature, and their plasma levels were measured by quantitative polymerase chain reaction (PCR). Forty metastatic breast cancer patients were chosen as the training groups. The potential significant microRNAs were validated in another 103 plasma samples. Results: In the training set, we identified 3 microRNAs (miR-200a, miR-210, and miR-451) as significantly dysregulated miRNAs between sensitive group (partial response (and stable disease) and resistant group (progressive disease). Then, in the validation set, miR-200a (area under the curve = 0.881, sensitivity = 94.1%, specificity = 76.7%) and miR-210 (area under the curve = 0.851, sensitivity = 88.2%, specificity = 72.1%) showed high diagnostic accuracy for distinguishing sensitive group from resistant group. Furthermore, the plasma level of miR-200a was significantly associated with the stage in surgery ( P = .035), and the high level of miR-210 expression was associated with internal organ metastasis (liver, lung, and brain; P = .024). Conclusions: Plasma miR-200a and miR-210 could be effective biomarkers for the prediction of chemotherapy resistance in metastatic breast cancer patients.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3131-3131
Author(s):  
Naeem Tahir ◽  
Jerome H. Goldschmidt ◽  
Eva Culakova ◽  
Marek S. Poniewierski ◽  
Debra A. Wolff ◽  
...  

Abstract Introduction: Although 60% of all malignancies occur in patients ≥65, this population is poorly represented in cancer clinical trials. While fit elderly patients appear to tolerate chemotherapy as well as younger individuals, less is known about chemotherapy tolerance in older cancer patients with poor performance status or co-morbidities. The purpose of this study was to examine the impact of patient and disease characteristics on the reported toxicities of cancer chemotherapy. Methods: This study represents part of a prospective, nationwide registry based at 137 randomly selected practice sites throughout the US. The major malignancies considered were cancers of the breast (33%), colon (10%), lung (19%) and ovary (7%) along with malignant lymphoma (8%). To date, 3422 patients have been registered of which 2719 are available for analysis including 1083 patients age ≥65 (40%). Primary outcome measures were: relative dose intensity (RDI) compared to standard doses, anemia (Hgb &lt;10), neutropenia (neutrophils &lt;1000) and non-hematologic toxicities pertinent to older adults including stomatitis, diarrhea, anorexia, dehydration and weight loss. Univariate and multivariate logistic regression analysis was performed to compare the difference between the 65–74 and ≥75 age groups. Results: Complete data were available on 927 patients ≥65 years of age. Among breast cancer patients, increasing age (&lt;65, 65–74, ≥75) was associated with progressively less Grade III/IV neutropenia (62%, 51% and 41%), respectively (p=0.006). This corresponds to patients receiving progressively less RDI (93.4%, 91.3%, 89.8%; P=.025) with 17%, 19% and 25% receiving RDI &lt;85%, respectively. Most of the reduced RDI was planned in patients ≥75 years compared with less than half in younger patients (P=.035). Non-breast cancer patients experienced no significant difference in rates of Grade III/IV neutropenia by age. Increasing age was associated with progressively more anemia (27%, 34%, and 44%) respectively (p&lt;0.0001) among non-breast cancer patients but not among those with breast cancer. Despite a trend, no significant increase in non-hematologic toxicities was observed with increasing age in breast cancer or non-breast cancer patients. Factors significantly associated with Grade III/IV neutropenia in univariate analysis included baseline ANC &lt;3000, BSA&lt;2.0, female gender and anthracycline containing regimens. In multivariate analysis, after adjusting for tumor type and performance status the following were significant predictors of Grade III/IV neutropenia: BSA&lt;2.0 (OR=1.5 p=0.04), Baseline ANC&lt;3000 (OR=2.0 p=0.001) and anthracycline containing regimen (OR=3.5 p&lt;0.0001). Factors associated with non-hematologic toxicity in univariate analysis included colon cancer (p&lt;0.0001), Charlson Co-morbidity Index (CCI) ≥ 3 (p=0.068), ECOG performance status ≥2 (p=0.05), and 5-Fluorouracil containing regimens (p&lt;0.0001) while in multivariate analysis, only the CCI maintained a trend towards increased non-hematologic toxicity (p=0.069). Conclusions: While anemia increases with age in non-breast cancer patients, neutropenia decreases with increasing age in breast cancer patients, most likely as a result of age-related reductions in RDI.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12014-e12014
Author(s):  
Sowmya Goranta ◽  
Tarek Haykal ◽  
Areeg Bala ◽  
Ragheed Al-Dulaimi ◽  
Ghassan Bachuwa ◽  
...  

e12014 Background: Oncotype-DX Assay is a 21-gene based recurrence score (RS) that helps stratify breast cancer patients based on their risk of recurrence. It is often used to help identify patients that may benefit from adjuvant chemotherapy (AC). Prior to the TAILORx Trial results, there were no guidelines for AC in patients with an intermediate score (18-30). Management of these patients was often at the clinical judgement of the provider. We sought to determine predictors of AC among these patients, and measure treatment effect on survival. Methods: We queried the Surveillance, Epidemiology, and End-Results database for breast cancer patients newly diagnosed between 2010-2015. We included patients with T1-T3, hormone receptor positive, HER2-negative, and lymph node-negative breast cancer with an intermediate RS. Male patients, those younger than 40 years, tumors 5 mm or less, and incomplete records were excluded. Univariate and multivariate analysis was performed to derive independent predictors of AC. Cox Proportional-Hazards Model was done to examine the effect of AC on survival. Results: We included 14,710 patients of whom 4,508 (30.6%) received AC. Patients that received AC were younger (55.4 years [8.8] vs 60.0 [9.7], p < 0.001), grade III or higher (29.8% vs 16.4%, p < 0.001), and had a higher RS (23.9 [3.6] vs 21.5 [3.1], p < 0.001). Higher T stage was associated with a higher rate of patients receiving AC (p < 0.001). Marital status was also associated with AC; a higher proportion of patients who received AC were married (67.9% vs 64.4%, p < 0.001). There was no significant association between race/ethnicity or insurance type with AC. Multivariate analysis showed that RS (OR: 1.24 [1.23-1.26], p < 0.001), T stage (OR: 1.67 [1.21-2.30], p < 0.001), and a grade III tumor (OR: 1.85 [1.64-2.09], p < 0.001) were the strongest predictors of AC. The age decile 80-89 years (OR: 0.05 [0.02-0.10], p < 0.001) was the most negative predictor of AC. AC did not have an effect on 5 year overall survival (97.6% vs 96.0%, p = 0.28). Conclusions: Between 2010-2015, our study shows 30.6% of breast cancers patients with an intermediate Oncotype-DX score were given AC. The decision to treat was largely based on tumor size, grade and age. AC had no effect on overall survival.


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