scholarly journals Early breast cancer screening using iron/iron oxide-based nanoplatforms with sub-femtomolar limits of detection

2016 ◽  
Vol 7 ◽  
pp. 364-373 ◽  
Author(s):  
Dinusha N Udukala ◽  
Hongwang Wang ◽  
Sebastian O Wendel ◽  
Aruni P Malalasekera ◽  
Thilani N Samarakoon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protease Activity ◽  
Early Cancer ◽  
Consensus Sequence ◽  
Tumor Biology ◽  
Surrounding Tissue ◽  
Breast Cancer Patients ◽  
Liquid Biopsies ◽  
Limits Of Detection ◽  
Early Cancer Diagnosis

Proteases, including matrix metalloproteinases (MMPs), tissue serine proteases, and cathepsins (CTS) exhibit numerous functions in tumor biology. Solid tumors are characterized by changes in protease expression levels by tumor and surrounding tissue. Therefore, monitoring protease levels in tissue samples and liquid biopsies is a vital strategy for early cancer detection. Water-dispersable Fe/Fe3O4-core/shell based nanoplatforms for protease detection are capable of detecting protease activity down to sub-femtomolar limits of detection. They feature one dye (tetrakis(carboxyphenyl)porphyrin (TCPP)) that is tethered to the central nanoparticle by means of a protease-cleavable consensus sequence and a second dye (Cy 5.5) that is directly linked. Based on the protease activities of urokinase plasminogen activator (uPA), MMPs 1, 2, 3, 7, 9, and 13, as well as CTS B and L, human breast cancer can be detected at stage I by means of a simple serum test. By monitoring CTS B and L stage 0 detection may be achieved. This initial study, comprised of 46 breast cancer patients and 20 apparently healthy human subjects, demonstrates the feasibility of protease-activity-based liquid biopsies for early cancer diagnosis.

scholarly journals Diagnostic potential of hypoxia-induced genes in liquid biopsies of breast cancer patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Carlos Henrique F. Peiró ◽  
Matheus M. Perez ◽  
Glauco S. A. de Aquino ◽  
Jéssica F. A. Encinas ◽  
Luiz Vinícius de A. Sousa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Glucose Transporter ◽  
Carbonic Anhydrases ◽  
Breast Cancer Patients ◽  
Gene Expressions ◽  
Liquid Biopsies ◽  
Healthy Women ◽  
Diagnostic Potential ◽  
Laboratory Tool

AbstractIn tumor cells, higher expression of glucose transporter proteins (GLUT) and carbonic anhydrases (CAIX) genes is influenced by hypoxia-induced factors (HIF).Thus, we aimed to study the expression profile of these markers in sequential peripheral blood collections performed in breast cancer patients in order to verify their predictive potential in liquid biopsies. Gene expressions were analyzed by qPCR in tumor and blood samples from 125 patients and 25 healthy women. Differential expression was determined by the 2(−ΔCq) method. Expression of HIF-1α and GLUT1 in the blood of breast cancer patients is significantly higher (90–91 and 160–161 fold increased expression, respectively; p < 0.0001) than that found in healthy women. Their diagnostic power was confirmed by ROC curve. CAIX is also more expressed in breast cancer women blood, but its expression was detected only in a few samples. But none of these genes could be considered predictive markers. Therefore, evaluation of the expression of HIF-1α and GLUT1 in blood may be a useful laboratory tool to complement the diagnosis of breast cancer, in addition to being useful for follow-up of patients and of women with a family history of breast cancer.

scholarly journals Exosomes: A Forthcoming Era of Breast Cancer Therapeutics

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4672
Author(s):  
Banashree Bondhopadhyay ◽  
Sandeep Sisodiya ◽  
Faisal Abdulrahman Alzahrani ◽  
Muhammed A. Bakhrebah ◽  
Atul Chikara ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Therapeutics ◽  
Therapeutic Strategies ◽  
Breast Cancer Patients ◽  
Liquid Biopsies ◽  
Non Invasive ◽  
Tumor Tissues ◽  
Circulating Markers

Despite the recent advancements in therapeutics and personalized medicine, breast cancer remains one of the most lethal cancers among women. The prognostic and diagnostic aids mainly include assessment of tumor tissues with conventional methods towards better therapeutic strategies. However, current era of gene-based research may influence the treatment outcome particularly as an adjunct to diagnostics by exploring the role of non-invasive liquid biopsies or circulating markers. The characterization of tumor milieu for physiological fluids has been central to identifying the role of exosomes or small extracellular vesicles (sEVs). These exosomes provide necessary communication between tumor cells in the tumor microenvironment (TME). The manipulation of exosomes in TME may provide promising diagnostic/therapeutic strategies, particularly in triple-negative breast cancer patients. This review has described and highlighted the role of exosomes in breast carcinogenesis and how they could be used or targeted by recent immunotherapeutics to achieve promising intervention strategies.

scholarly journals Clinical significance of serum PSA in breast cancer patients

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Toru Hanamura ◽  
Koichi Ohno ◽  
Shinya Hokibara ◽  
Hideki Murasawa ◽  
Toshitsugu Nakamura ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Tumor Biology ◽  
Specific Antigen ◽  
Metastatic Breast ◽  
Serum Testosterone ◽  
Biological Properties ◽  
Cancer Tissue ◽  
Breast Cancer Patients ◽  
Post Menopausal

Abstract Background Recent preclinical data suggest that androgen receptor (AR) signaling plays a significant role in subsets of breast cancer. Clinical trials testing AR-targeting therapies in breast cancer have been conducted. Assessment of AR-signal in breast cancer tissue maybe useful for treatment selections. Prostate specific antigen (PSA) is the product of an androgen-responsive gene. Serum PSA (sPSA) can be detected in women by a highly sensitive assay although the concentration is much lower than that observed in males. We investigated if sPSA reflects tumor biology, including AR signaling in breast cancer patients. Methods In this study, 132 healthy controls and 144 breast cancer patients were enrolled. sPSA was evaluated by the chemiluminescent enzyme immunoassay (CLEIA) method. Correlations between sPSA and the various clinicopathological factors were analyzed. Results In post-menopausal state, sPSA detection rate was significantly higher in breast cancer patients compared with controls (27.4% vs 11.3%: p = 0.0090), but not in the whole cohort (29.2% vs 25.8%: p = 0.5265) or pre-menopausal subgroup (37.0% vs 42.6%: p = 0.6231). In post-menopausal breast cancer cases, higher sPSA value was associated with clinic-pathological factors including the expression of AR protein in primary legion. In a correlation analysis of quantitative data limited to post-menopausal metastatic breast cancer (MBC), sPSA was positively, albeit weakly correlated with clinic-pathological features including serum testosterone levels and AR positivity. Conclusions Our data suggest that sPSA may reflect tumor biological properties including AR activity in post-menopausal breast cancer.

scholarly journals Identification of miRNAs Enriched in Extracellular Vesicles Derived from Serum Samples of Breast Cancer Patients

Biomolecules ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 150 ◽  
Author(s):  
Patricia M. M. Ozawa ◽  
Evelyn Vieira ◽  
Débora S. Lemos ◽  
Ingrid L. Melo Souza ◽  
Silvio M. Zanata ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Extracellular Vesicles ◽  
Area Under The Curve ◽  
Precipitation Method ◽  
Sequencing Analysis ◽  
Breast Cancer Patients ◽  
Serum Samples ◽  
Luminal A ◽  
Liquid Biopsies ◽  
Advanced Tumor

MicroRNAs derived from extracellular vesicles (EV-miRNAs) are circulating miRNAs considered as potential new diagnostic markers for cancer that can be easily detected in liquid biopsies. In this study, we performed RNA sequencing analysis as a screening strategy to identify EV-miRNAs derived from serum of clinically well-annotated breast cancer (BC) patients from the south of Brazil. EVs from three groups of samples (healthy controls (CT), luminal A (LA), and triple-negative (TNBC)) were isolated from serum using a precipitation method and analyzed by RNA-seq (screening phase). Subsequently, four EV-miRNAs (miR-142-5p, miR-150-5p, miR-320a, and miR-4433b-5p) were selected to be quantified by quantitative real-time PCR (RT-qPCR) in individual samples (test phase). A panel composed of miR-142-5p, miR-320a, and miR-4433b-5p distinguished BC patients from CT with an area under the curve (AUC) of 0.8387 (93.33% sensitivity, 68.75% specificity). The combination of miR-142-5p and miR-320a distinguished LA patients from CT with an AUC of 0.9410 (100% sensitivity, 93.80% specificity). Interestingly, decreased expression of miR-142-5p and miR-150-5p were significantly associated with more advanced tumor grades (grade III), while the decreased expression of miR-142-5p and miR-320a was associated with a larger tumor size. These results provide insights into the potential application of EVs-miRNAs from serum as novel specific markers for early diagnosis of BC.

Race as an independent factor for survival in breast cancer patients according to analysis of the National Cancer Database (NCDB).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e18155-e18155 ◽  
Author(s):  
Drew Carl Drennan Murray ◽  
Shruti Bhandari ◽  
Phuong Ngo ◽  
Sarah Mudra ◽  
Rachana Shirish Lele ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Proportional Hazards ◽  
Early Stage ◽  
Tumor Biology ◽  
Multivariable Analysis ◽  
Cox Proportional Hazards ◽  
Independent Factor ◽  
Breast Cancer Patients ◽  
Delayed Treatment

e18155 Background: Black (B) women after early stage of diagnosis have been shown to have double the risk of white (W) women for failing to receive adjuvant chemotherapy. Despite lower incidence of breast cancer in B patients, they are more likely to die of the disease. Worse outcomes in B populations have been related to clinical and socioeconomic factors. However, the determination of improved access and its effects on survival in black patients remains uncertain. Methods: 1042844 patients diagnosed between 2004 and 2014 with stage I-III breast cancer were identified in the NCDB. Only W and B races were analyzed with established risk factors of age, stage, comorbidity score, and insurance status. Data was analyzed using univariable and multivariable logistic and Cox proportional hazards regression models. Odds Ratio (OR) for binary outcome, Hazard Ratio (HR) for time-to-event (survival) outcome along with 95% confidence interval (95% CI) are reported. Results: Among the total population 85.5% were W, 10.6% B, and 3.9% other. B were more likely to be uninsured (OR: 1.66; 95% CI: 1.59 - 1.72; p < 0.0001), or have Medicaid (OR: 2.01; 95% CI: 1.96 - 2.07; p < 0.0001). B were also diagnosed at later stage (stage 3 OR: 1.59; 95% CI: 1.57 - 1.63; p < 0.0001) with higher co-morbidities (OR: 2.49; 95% CI: 2.34 - 2.67; p < 0.0001) consistent with prior studies. B were more likely to experience delayed treatment (OR: 2.15; 95% CI: 2.10 - 2.20; p < 0.0001). B race remained an independent factor associated with higher likelihood of death compared to W patients (HR: 1.32; 95% CI: 1.3 - 1.34; p < 0.0001) in multivariable analysis. Conclusions: This large database study demonstrates that even when controlling for established risk factors such lack of insurance or Medicaid, higher comorbidities, and later stage at diagnosis, B patients were more likely to experience delays in treatment initiation and worse overall survival. This suggests race remains an independent risk factor for poor outcome even when clinical factors are matched. Further analysis including tumor biology should be examined to better understand this persistent disparity.

Factors associated with axillary conversion after neoadjuvant chemotherapy in initially node positive breast cancer patients: A transSENTINA analysis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 567-567
Author(s):  
Hans-Christian Kolberg ◽  
Thorsten Kühn ◽  
Maja Krajewska ◽  
Ingo Bauerfeind ◽  
Tanja N. Fehm ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Lymph Nodes ◽  
Primary Tumor ◽  
Tumor Biology ◽  
Her2 Status ◽  
Tumor Diameter ◽  
Breast Cancer Patients ◽  
Axillary Surgery ◽  
Small Patient Number

567 Background: Current study concepts in early breast cancer after neoadjuvant chemotherapy (NAT) are aiming at reducing morbidity by omission of axillary surgery in selected patients. Selection criteria for this strategy have to include the probability of conversion from cN1 to ycN0. We analyzed the association of clinical/pathological parameters and axillary conversion with data from arms C and D of the SENTINA trial (Kühn T et al., Lancet Oncol 2013). Methods: Patients were recruited to Arms C/D of the SENTINA trial in case they presented with clinically positive nodes before NAT. Based on their response to NAT they were then assigned to either arm C (clinically conversion to ycN0) or arm D (no clinical conversion (ycN+). In both the pre- and post-NAT scenarios, clinically involved lymph nodes were defined as palpable and/or suspect by ultrasound. Univariate logistic regression analyses were carried out to evaluate the association between clinical/pathological parameters and axillary conversion after NAT. Results: Of the 892 patients in arms C and D of the SENTINA trial 716 were evaluable for this analysis. After NAT, 593 patients converted to ycN0 and were therefore assigned to arm C; in contrast, 123 patients still had involved lymph nodes after NAT (ycN+) and were assigned to Arm D. Arms C and D were compared regarding the clinical/pathological parameters tumor diameter by ultrasound before and after NAT, grading, multifocality, ER status, PR status, HER2 status, pathological complete remission in the breast (breast pCR), morphology, lymphovascular invasion (LVI) and hemangiosis. Only small tumor diameter after NAT (p = 0.0038), achievement of breast pCR (p = 0.0001) and lack of LVI (p = 0.0009) were positively associated with axillary conversion from cN1 to ycN0 after NAT. Conclusions: Because of the small patient number in arm D, we were not able to identify an association between parameters of tumor biology (ER, PR, HER2 and TN status) and axillary conversion. However, favorable response of the primary tumor (represented both clinically by tumor diameter after NAT and pathologically by pCR in the breast) were positively associated with conversion from cN1 to ycN0. These results justify including patients with clinical and pathological response of the primary tumor in trials investigating de-escalation of axillary surgery after NAT.

scholarly journals P6: CIRCULATING MICRORNA PATTERN DEFINES A BIOLOGICALLY DISTINCT BREAST CANCER PATTERN IN BLACK (B) WOMEN RELATIVE TO ONE CCCURRING IN WHITE (W) WOMEN

2016 ◽  
Vol 64 (3) ◽  
pp. 819.2-819
Author(s):  
I Shapira ◽  
P Daksharam ◽  
V Kremer ◽  
A Banavali ◽  
M Kopf ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Black Women ◽  
Ovarian Tissue ◽  
Tumor Biology ◽  
Survival Rates ◽  
Tissue Bank ◽  
Integrated Approach ◽  
Circulating Microrna ◽  
Breast Cancer Patients ◽  
Lower Survival

Purpose of StudyBlack women with triple negative breast cancer have 46% lower survival rates attributed to differences in tumor biology. We analyzed presurgical plasma microRNA of white (W) and black (B) women with TNBC enrolled in our breast ovarian tissue bank between 2004 and 2014.AimsDetect microRNA patterns in pre-surgical plasma of TNBC W or B Analyze differences by integrated approach to detect pathways differentially activated in the two groups.Methods UsedBetween 2004 and 2014 we investigated patterns of plasma miRNAs collected before, after surgery, during and after chemotherapy in 67 patients presenting for surgery for breast cancer (W=44 & B=44) and 25 age and race matched normal controls. Two-sample t-test was used for all 2-sample comparison and ANOVA followed by Benjamin Hochberg post-hoc test to compare the mean response between subject factors of interest. All tests were 2-tailed and results with a p<0.05 were considered statistically significant. Coremine was used to identify datasets in breast cancer microarray with emphasis on our differentially expressed circulating miRs.Summary of ResultsMean age cancer 48 (range 35–78), control 44 (range 35–67): B patients did not express over 70% of pre-surgical plasma miRs over-expressed in the W pre-surgical plasma. Black patients had lower expression of MiRs: −16-5p, −484, −126, −150-5p, −142-3p; −30c-5p, −186-5p, 139-5p. Samples from white patients overexpressed miRs−126, −150-5p, −142-3p; −30c-5p, −186-5p, 139-5p compared to healthy controls. These miRs significantly suppressed in blacks p<0.05.Coremine text mining suggests differentially regulated microRNA are involved in mitochondrial quality control and biogenesis.ConclusionsDeregulation in circulating miRs between B and W patients point to pathways involved in mitochondrial fission and fusion. Aberrant mitochondria biogenesis was reported as mechanism for cancer stem cell survival and detrimental to innate immunity. Such pathways could explain the lower survival seen in black breast cancer patients.

scholarly journals To Look or Not to Look? Yes to Nodal US!

2021 ◽  
Author(s):  
Gaiane M Rauch ◽  
Henry M Kuerer ◽  
Maxine S Jochelson
Keyword(s):  
Breast Cancer ◽  
Systemic Therapy ◽  
Tumor Biology ◽  
Significant Proportion ◽  
Nodal Status ◽  
Newly Diagnosed ◽  
Breast Cancer Patients ◽  
Axillary Surgery ◽  
Appropriate Treatment ◽  
Neoadjuvant Systemic Therapy

Abstract Knowledge of axillary nodal status is highly important for correct staging and treatment planning in patients with breast cancer. Axillary US is a recognized highly specific and cost-effective tool for assessing nodal status and guiding appropriate treatment. Axillary US imaging with US-guided biopsy is routinely performed throughout the world. However, because of recent developments in the surgical management of the axilla in patients with newly diagnosed breast cancer (American College of Surgeons Oncology Group [ACOSOG] Z0011 trial) and in patients with breast cancer receiving neoadjuvant systemic therapy (ACOSOG Z1071, SENTinel NeoAdjuvant [SENTINA] and Sentinel Node biopsy aFter NeoAdjuvant Chemotherapy [SN FNAC] trials), some have questioned the utility of axillary US for nodal staging. Here, we review the evidence to date supporting the additional value of axillary US for patients with breast cancer. Nodal US in patients with newly diagnosed breast cancer is useful for staging; in a significant proportion of patients, nodal US identifies additional axillary level II or level III nodal disease, which allows for appropriate treatment of disease. Furthermore, ongoing clinical trials may show that axillary surgery can be omitted in patients with negative findings on axillary US. In patients with lymph node–positive disease undergoing neoadjuvant systemic therapy, nodal US can guide the approach to axillary surgery. A more personalized patient approach, taking into the account tumor biology, among other factors, may help to mitigate the controversy surrounding the role of axillary US in breast cancer patients.

scholarly journals Detecting the “gist” of breast cancer in mammograms three years before localized signs of cancer are visible

2019 ◽  
Vol 92 (1099) ◽  
pp. 20190136 ◽  
Author(s):  
Karla K. Evans ◽  
Anne-Marie Culpan ◽  
Jeremy M. Wolfe
Keyword(s):  
Breast Cancer ◽  
Breast Density ◽  
Cancer Diagnosis ◽  
Operating Characteristic ◽  
Receiver Operating Characteristic Analysis ◽  
Early Cancer ◽  
Elevated Risk ◽  
Characteristic Analysis ◽  
Early Cancer Diagnosis ◽  
Large Numbers

Objectives: After a 500 ms presentation, experts can distinguish abnormal mammograms at above chance levels even when only the breast contralateral to the lesion is shown. Here, we show that this signal of abnormality is detectable 3 years before localized signs of cancer become visible. Methods: In 4 prospective studies, 59 expert observers from 3 groups viewed 116–200 bilateral mammograms for 500 ms each. Half of the images were prior exams acquired 3 years prior to onset of visible, actionable cancer and half were normal. Exp. 1D included cases having visible abnormalities. Observers rated likelihood of abnormality on a 0–100 scale and categorized breast density. Performance was measured using receiver operating characteristic analysis. Results: In all three groups, observers could detect abnormal images at above chance levels 3 years prior to visible signs of breast cancer (p < 0.001). The results were not due to specific salient cases nor to breast density. Performance was correlated with expertise quantified by the number of mammographic cases read within a year. In Exp. 1D, with cases having visible actionable pathology included, the full group of readers failed to reliably detect abnormal priors; with the exception of a subgroup of the six most experienced observers. Conclusions: Imaging specialists can detect signals of abnormality in mammograms acquired years before lesions become visible. Detection may depend on expertise acquired by reading large numbers of cases. Advances in knowledge: Global gist signal can serve as imaging risk factor with the potential to identify patients with elevated risk for developing cancer, resulting in improved early cancer diagnosis rates and improved prognosis for females with breast cancer.

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