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1.
Breast Cancer Res Treat ; 192(2): 265-271, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1750749

ABSTRACT

PURPOSE: To compare participants' knowledge about gene expression profiling (GEP) tests and recurrence risks after reading an information leaflet with that following viewing of an information film. METHODS: Using a randomised cross-over design, at time-point one (T1), women aged 45-75 years without breast cancer either read leaflets or watched information films about Oncotype DX or Prosigna tests. Participants answered nine questions assessing knowledge (maximum score 18). Next-day information in the opposite modality was provided and knowledge re-assessed. Additional questions probed which format was easiest to understand, participants' preferences for film or leaflet and their reasons for these. RESULTS: 120 women participated (60 received OncotypeDX films and leaflets; 60 received the Prosigna versions). T1 mean knowledge scores were higher following film viewing (13.37) compared with that after reading leaflets (9.25) (mean difference 4.1; p < 0.0001; 95% CI 3.2, 5.0). When participants read leaflets first and subsequently viewed films, all increased their scores (mean + 6.08, from T1 of 9.25, p < 0.0001; 95% CI 5.44, 6.72). When films were viewed first, followed by leaflets, (36/60, 60%), participants' scores declined (mean-1.55 from T1 of 13.37, p < 0.001; 95% CI -2.32, -0.78). A majority of participants expressed preferences for the films (88/120, 73.3%) irrespective as to whether they described OncotypeDX or Prosigna. Reasons included the clarity, ease of understanding, visual material and reassuring voice-over. CONCLUSION: Discussions between oncologists and patients about recurrence risk results can be challenging. Information leaflets may aid understanding but often employ complex language. Information films significantly improved knowledge and were preferred by participants.


Subject(s)
Breast Neoplasms , Aged , Breast Neoplasms/diagnosis , Breast Neoplasms/genetics , Cross-Over Studies , Female , Gene Expression Profiling , Humans , Middle Aged
2.
Int J Mol Sci ; 22(16)2021 Aug 20.
Article in English | MEDLINE | ID: covidwho-1662689

ABSTRACT

Breast cancer continues to be one of the main causes of morbidity and mortality globally and was the leading cause of cancer death in women in Spain in 2020. Early diagnosis is one of the most effective methods to lower the incidence and mortality rates of breast cancer. The human metalloproteinases (MMP) mainly function as proteolytic enzymes degrading the extracellular matrix and plays important roles in most steps of breast tumorigenesis. This retrospective cohort study shows the immunohistochemical expression levels of MMP-1, MMP-2, MMP-3, and MMP-9 in 154 women with breast cancer and 42 women without tumor disease. The samples of breast tissue are assessed using several tissue matrices (TMA). The percentages of staining (≤50%->50%) and intensity levels of staining (weak, moderate, or intense) are considered. The immunohistochemical expression of the MMP-1-intensity (p = 0.043) and MMP-3 percentage (p = 0.018) and intensity, (p = 0.025) present statistically significant associations with the variable group (control-case); therefore, expression in the tumor tissue samples of these MMPs may be related to the development of breast cancer. The relationships between these MMPs and some clinicopathological factors in breast cancer are also evaluated but no correlation is found. These results suggest the use of MMP-1 and MMP-3 as potential biomarkers of breast cancer diagnosis.


Subject(s)
Breast Neoplasms/metabolism , Matrix Metalloproteinase 1/metabolism , Matrix Metalloproteinase 3/metabolism , Aged , Aged, 80 and over , Biomarkers, Tumor/genetics , Breast/pathology , Breast Neoplasms/diagnosis , Breast Neoplasms/genetics , Case-Control Studies , Cohort Studies , Disease Progression , Female , Humans , Immunohistochemistry/methods , Matrix Metalloproteinase 1/genetics , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 3/genetics , Matrix Metalloproteinase 9/metabolism , Metalloproteases/genetics , Metalloproteases/metabolism , Middle Aged , Retrospective Studies , Spain , Tissue Inhibitor of Metalloproteinases/metabolism
3.
Anal Chem ; 94(3): 1626-1636, 2022 01 25.
Article in English | MEDLINE | ID: covidwho-1621191

ABSTRACT

(Mi)RNAs are important biomarkers for cancers diagnosis and pandemic diseases, which require fast, ultrasensitive, and economical detection strategies to quantitatively detect exact (mi)RNAs expression levels. The novel coronavirus disease (SARS-CoV-2) has been breaking out globally, and RNA detection is the most effective way to identify the SARS-CoV-2 virus. Here, we developed an ultrasensitive poly-l-lysine (PLL)-functionalized graphene field-effect transistor (PGFET) biosensor for breast cancer miRNAs and viral RNA detection. PLL is functionalized on the channel surface of GFET to immobilize DNA probes by the electrostatic force. The results show that PGFET biosensors can achieve a (mi)RNA detection range of five orders with a detection limit of 1 fM and an entire detection time within 20 min using 2 µL of human serum and throat swab samples, which exhibits more than 113% enhancement in terms of sensitivity compared to that of GFET biosensors. The performance enhancement mechanisms of PGFET biosensors were comprehensively studied based on an electrical biosensor theoretical model and experimental results. In addition, the PGFET biosensor was applied for the breast cancer miRNA detection in actual serum samples and SARS-CoV-2 RNA detection in throat swab samples, providing a promising approach for rapid cancer diagnosis and virus screening.


Subject(s)
Biosensing Techniques , Breast Neoplasms , COVID-19 , Graphite , MicroRNAs , Breast Neoplasms/diagnosis , Breast Neoplasms/genetics , COVID-19/diagnosis , Female , Humans , Polylysine , RNA, Viral/genetics , SARS-CoV-2
4.
J Surg Oncol ; 125(4): 596-602, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1592572

ABSTRACT

BACKGROUND AND OBJECTIVES: With increased neoadjuvant therapy recommendations for early-stage breast cancer patients due to the COVID-19 pandemic, it is imperative that molecular diagnostic assays provide reliable results from preoperative core needle biopsies (CNB). The study objective was to determine the concordance of MammaPrint and BluePrint results between matched CNB and surgical resection (SR) specimens. METHODS: Matched tumor specimens (n = 121) were prospectively collected from women enrolled in the FLEX trial (NCT03053193). Concordance is reported using overall percentage agreement and Cohen's kappa coefficient. Correlation is reported using Pearson correlation coefficient. RESULTS: We found good concordance for MammaPrint results between matched tumor samples (90.9%, κ = 0.817), and a very strong correlation of MammaPrint indices (r = 0.94). The concordance of BluePrint subtyping in matched samples was also excellent (98.3%). CONCLUSIONS: CNB samples demonstrated high concordance with paired SR samples for MammaPrint risk classification and BluePrint molecular subtyping, suggesting that physicians are provided with accurate prognostic information that can be used to guide therapy decisions.


Subject(s)
Biomarkers, Tumor/genetics , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Clinical Decision Rules , Genomics , Adult , Aged , Aged, 80 and over , Biopsy, Large-Core Needle , Breast Neoplasms/surgery , Female , Humans , Middle Aged , Neoplasm Staging , Prognosis , Prospective Studies , Reproducibility of Results , Risk Assessment
6.
Int J Biol Sci ; 17(12): 3224-3238, 2021.
Article in English | MEDLINE | ID: covidwho-1524470

ABSTRACT

Mechanisms of breast cancer progression and invasion, often involve alteration of hormonal signaling, and upregulation and/or activation of signal transduction pathways that input to cell cycle regulation. Herein, we describe a rationally designed first-in-class novel small molecule inhibitor for targeting oncogenic and hormonal signaling in ER-positive breast cancer. BC-N102 treatment exhibits dose-dependent cytotoxic effects against ER+ breast cancer cell lines. BC-N102 exhibited time course- and dose-dependent cell cycle arrest via downregulation of the estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), phosphatidylinositol 3-kinase (PI3K), phosphorylated (p)-extracellular signal-regulated kinase (ERK), p-Akt, CDK2, and CDK4 while increasing p38 mitogen-activated protein kinase (MAPK), and mineralocorticoid receptor (MR) signaling in breast cancer cell line. In addition, we found that BC-N102 suppressed breast cancer tumorigenesis in vivo and prolonged the survival of animals. Our results suggest that the proper application of BC-N102 may be a beneficial chemotherapeutic strategy for ER+ breast cancer patients.


Subject(s)
Antineoplastic Agents/pharmacology , Breast Neoplasms/drug therapy , Cell Cycle Checkpoints/drug effects , Cell Cycle Proteins/metabolism , G1 Phase/drug effects , Receptors, Estrogen/metabolism , Resting Phase, Cell Cycle/drug effects , Animals , Biomarkers, Tumor/genetics , Blotting, Western , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cell Division , Cell Line, Tumor , Cyclin-Dependent Kinase 2/genetics , Cyclin-Dependent Kinase 4/genetics , Female , Flow Cytometry , Gene Expression Regulation, Neoplastic/physiology , Humans , Maximum Tolerated Dose , Mice , Mice, Nude , Xenograft Model Antitumor Assays
7.
Cancer Res Treat ; 53(3): 650-656, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1403959

ABSTRACT

PURPOSE: Coronavirus disease 2019 (COVID-19) pandemic has spread worldwide rapidly and patients with cancer have been considered as a vulnerable group for this infection. This study aimed to examine the expressions of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) in tumor tissues of six common cancer types. MATERIALS AND METHODS: The expression levels of ACE2 and TMPRSS2 in tumors and control samples were obtained from online databases. Survival prognosis and biological functions of these genes were investigated for each tumor type. RESULTS: There was the overexpression of ACE2 in colon and stomach adenocarcinomas compared to controls, meanwhile colon and prostate adenocarcinomas showed a significantly higher expression of TMPRSS2. Additionally, survival prognosis analysis has demonstrated that upregulation of ACE2 in liver hepatocellular carcinoma was associated with higher overall survival (hazard ratio, 0.65; p=0.016) and disease-free survival (hazard ratio, 0.66; p=0.007), while overexpression of TMPRSS2 was associated with a 26% reduced risk of death in lung adenocarcinoma (p=0.047) but 50% increased risk of death in breast invasive carcinoma (p=0.015). CONCLUSION: There is a need to take extra precautions for COVID-19 in patients with colorectal cancer, stomach cancer, and lung cancer. Further information on other types of cancer at different stages should be investigated.


Subject(s)
Angiotensin-Converting Enzyme 2/genetics , COVID-19/diagnosis , Neoplasms/diagnosis , Neoplasms/genetics , Serine Endopeptidases/genetics , Adenocarcinoma/complications , Adenocarcinoma/diagnosis , Adenocarcinoma/epidemiology , Adenocarcinoma/genetics , Breast Neoplasms/complications , Breast Neoplasms/diagnosis , Breast Neoplasms/epidemiology , Breast Neoplasms/genetics , COVID-19/complications , COVID-19/epidemiology , COVID-19/genetics , Case-Control Studies , Databases as Topic , Female , Gastrointestinal Neoplasms/complications , Gastrointestinal Neoplasms/diagnosis , Gastrointestinal Neoplasms/epidemiology , Gastrointestinal Neoplasms/genetics , Gene Expression Regulation, Neoplastic , Genetic Predisposition to Disease , Humans , Liver Neoplasms/complications , Liver Neoplasms/diagnosis , Liver Neoplasms/epidemiology , Liver Neoplasms/genetics , Lung Neoplasms/complications , Lung Neoplasms/diagnosis , Lung Neoplasms/epidemiology , Lung Neoplasms/genetics , Male , Mutation , Neoplasms/complications , Neoplasms/epidemiology , Pandemics , Prognosis , Prostatic Neoplasms/complications , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/epidemiology , Prostatic Neoplasms/genetics , Retrospective Studies , SARS-CoV-2/physiology , Survival Analysis
8.
Cancer Treat Res Commun ; 27: 100321, 2021.
Article in English | MEDLINE | ID: covidwho-1385378

ABSTRACT

BACKGROUND: ACE2 a key molecule of the Renin-Angiotensin system has been identified as the receptor for SARS-CoV-2 entry into human cells. In the context of human cancers, there is evidence that ACE2 might function as a tumor suppressor. The expression levels of ACE2 among the different subtypes of breast cancer has not been investigated. METHODS: We have examined the differential expression of ACE2 and its correlation with prognosis in breast cancer subtypes using the METABRIC (n = 1898) and TCGA (n = 832) cohorts. Correlations were evaluated by Pearsons's correlation co-efficient and Kaplan-Meier analysis was used to estimate differences in disease-free survival between the ACE2 high and ACE2 low groups. RESULTS: There is minimal expression of ACE2 in the luminal classes, but significantly higher levels in the Basal-like and HER2-enriched subclasses. Metastatic biopsies of these tumor types also show enhanced expression of ACE2. High levels of ACE2 correlated with decreased disease-free survival in the HER2-enriched subtype, and it was positively correlated with EGFR expression. CONCLUSION: These observations suggest ACE2 might function as a context dependent factor driving tumor progression in breast cancer and permit new opportunities for targeted therapy.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , Biomarkers, Tumor/metabolism , Breast Neoplasms/metabolism , Receptor, ErbB-2/metabolism , Angiotensin-Converting Enzyme 2/genetics , Biomarkers, Tumor/genetics , Breast Neoplasms/genetics , Breast Neoplasms/therapy , Cohort Studies , Female , Humans , Kaplan-Meier Estimate , Middle Aged , Multivariate Analysis , Prognosis
9.
Int J Mol Sci ; 22(14)2021 Jul 12.
Article in English | MEDLINE | ID: covidwho-1308363

ABSTRACT

The cytoskeletal protein vimentin is secreted under various physiological conditions. Extracellular vimentin exists primarily in two forms: attached to the outer cell surface and secreted into the extracellular space. While surface vimentin is involved in processes such as viral infections and cancer progression, secreted vimentin modulates inflammation through reduction of neutrophil infiltration, promotes bacterial elimination in activated macrophages, and supports axonal growth in astrocytes through activation of the IGF-1 receptor. This receptor is overexpressed in cancer cells, and its activation pathway has significant roles in general cellular functions. In this study, we investigated the functional role of extracellular vimentin in non-tumorigenic (MCF-10a) and cancer (MCF-7) cells through the evaluation of its effects on cell migration, proliferation, adhesion, and monolayer permeability. Upon treatment with extracellular recombinant vimentin, MCF-7 cells showed increased migration, proliferation, and adhesion, compared to MCF-10a cells. Further, MCF-7 monolayers showed reduced permeability, compared to MCF-10a monolayers. It has been shown that the receptor binding domain of SARS-CoV-2 spike protein can alter blood-brain barrier integrity. Surface vimentin also acts as a co-receptor between the SARS-CoV-2 spike protein and the cell-surface angiotensin-converting enzyme 2 receptor. Therefore, we also investigated the permeability of MCF-10a and MCF-7 monolayers upon treatment with extracellular recombinant vimentin, and its modulation of the SARS-CoV-2 receptor binding domain. These findings show that binding of extracellular recombinant vimentin to the cell surface enhances the permeability of both MCF-10a and MCF-7 monolayers. However, with SARS-CoV-2 receptor binding domain addition, this effect is lost with MCF-7 monolayers, as the extracellular vimentin binds directly to the viral domain. This defines an influence of extracellular vimentin in SARS-CoV-2 infections.


Subject(s)
Breast Neoplasms/pathology , Breast/pathology , Cell Membrane Permeability , Extracellular Matrix/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Vimentin/metabolism , Breast/metabolism , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Cells, Cultured , Female , Humans , Protein Domains , Spike Glycoprotein, Coronavirus/genetics , Vimentin/genetics
10.
Aging (Albany NY) ; 13(13): 16904-16921, 2021 07 06.
Article in English | MEDLINE | ID: covidwho-1298261

ABSTRACT

Abnormal ATPase H+ Transporting Accessory Protein 1 (ATP6AP1) expression may promote carcinogenesis. We investigated the association of ATP6AP1 with breast cancer (BC) and COVID-19. The Oncomine, Gene Expression Profiling Interactive Analysis, Human Protein Atlas and Kaplan-Meier plotter databases were used to evaluate the expression and prognostic value of ATP6AP1 in BC. ATP6AP1 was upregulated in BC tissues, and higher ATP6AP1 expression was associated with poorer outcomes. Data from the Tumor Immune Estimation Resource, Tumor-Immune System Interaction Database and Kaplan-Meier plotter indicated that ATP6AP1 expression correlated with immune infiltration, and that its prognostic effects in BC depended on tumor-infiltrating immune cell subtype levels. Multiple databases were used to evaluate the association of ATP6AP1 with clinicopathological factors, assess the mutation and methylation of ATP6AP1, and analyze gene co-expression and enrichment. The ATP6AP1 promoter was hypomethylated in BC tissues and differentially methylated between different disease stages and subtypes. Data from the Gene Expression Omnibus indicated that ATP6AP1 levels in certain cell types were reduced after SARS-CoV-2 infections. Ultimately, higher ATP6AP1 expression was associated with a poorer prognosis and with higher or lower infiltration of particular immune cells in BC. BC patients may be particularly susceptible to SARS-CoV-2 infections, which may alter their prognoses.


Subject(s)
Biomarkers, Tumor/analysis , Breast Neoplasms/genetics , COVID-19/genetics , Vacuolar Proton-Translocating ATPases/genetics , Breast Neoplasms/diagnosis , Breast Neoplasms/immunology , COVID-19/diagnostic imaging , COVID-19/immunology , DNA Methylation , Female , Gene Expression Regulation, Enzymologic , Gene Expression Regulation, Neoplastic , Humans , Kaplan-Meier Estimate , Male , Mutation/genetics , Predictive Value of Tests , Prognosis , Survival Analysis , Treatment Outcome , Vacuolar Proton-Translocating ATPases/analysis , Vacuolar Proton-Translocating ATPases/immunology
11.
Curr Opin Obstet Gynecol ; 33(1): 53-58, 2021 02 01.
Article in English | MEDLINE | ID: covidwho-1066445

ABSTRACT

PURPOSE OF REVIEW: The present review summarizes recent original publications addressing the topic of risk-adapted adjuvant therapy in early breast cancer (EBC). As neoadjuvant therapy has become a standard for triple negative and HER2+ EBC, it focusses on luminal EBC. RECENT FINDINGS: Gene expression assays have become standard of care in luminal EBC, at least for patients with node negative disease. Two prospective randomized clinical trials, TAILORx (Oncotype DX) and MINDACT (MammaPrint) have presented additional analyses underlining the clinical utility of the tests. In times of COVID-19, immunohistochemically determined ER, PR, and Ki67 and early Ki67 response to endocrine therapy can be used to safely allocate patients for preoperative endocrine therapy and delay surgeries if resources are scarce. In patients with luminal high-risk disease, adding a CDK 4/6 inhibitor (abemaciclib) improves patient outcome already after short-term follow-up. SUMMARY: Determination of recurrence risk will remain important in luminal EBC for optimal therapy decisions. In the future, risk-adapted treatment concepts will include decision making for chemotherapy but also for endocrine-based approaches.


Subject(s)
Antineoplastic Agents, Hormonal/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , COVID-19/epidemiology , Protein Kinase Inhibitors/therapeutic use , Aminopyridines/therapeutic use , Benzimidazoles/therapeutic use , Breast Neoplasms/pathology , Breast Neoplasms/surgery , Female , Gene Expression Profiling , Humans , Ki-67 Antigen/metabolism , Neoadjuvant Therapy , Piperazines/therapeutic use , Pyridines/therapeutic use , Receptor, ErbB-2/genetics , Receptor, ErbB-2/metabolism , Receptors, Estrogen/genetics , Receptors, Estrogen/metabolism , Receptors, Progesterone/genetics , Receptors, Progesterone/metabolism , Risk Assessment , SARS-CoV-2
12.
Nucleic Acids Res ; 49(7): e37, 2021 04 19.
Article in English | MEDLINE | ID: covidwho-1066376

ABSTRACT

Multiple driver genes in individual patient samples may cause resistance to individual drugs in precision medicine. However, current computational methods have not studied how to fill the gap between personalized driver gene identification and combinatorial drug discovery for individual patients. Here, we developed a novel structural network controllability-based personalized driver genes and combinatorial drug identification algorithm (CPGD), aiming to identify combinatorial drugs for an individual patient by targeting personalized driver genes from network controllability perspective. On two benchmark disease datasets (i.e. breast cancer and lung cancer datasets), performance of CPGD is superior to that of other state-of-the-art driver gene-focus methods in terms of discovery rate among prior-known clinical efficacious combinatorial drugs. Especially on breast cancer dataset, CPGD evaluated synergistic effect of pairwise drug combinations by measuring synergistic effect of their corresponding personalized driver gene modules, which are affected by a given targeting personalized driver gene set of drugs. The results showed that CPGD performs better than existing synergistic combinatorial strategies in identifying clinical efficacious paired combinatorial drugs. Furthermore, CPGD enhanced cancer subtyping by computationally providing personalized side effect signatures for individual patients. In addition, CPGD identified 90 drug combinations candidates from SARS-COV2 dataset as potential drug repurposing candidates for recently spreading COVID-19.


Subject(s)
Algorithms , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Drug Therapy, Combination , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Precision Medicine/methods , Breast Neoplasms/classification , COVID-19/drug therapy , COVID-19/genetics , Datasets as Topic , Drug Repositioning , Drug Synergism , Drug-Related Side Effects and Adverse Reactions , Gene Expression Regulation, Neoplastic/genetics , Genes, Neoplasm/genetics , Humans , Risk Assessment , Workflow
13.
Curr Opin Obstet Gynecol ; 33(1): 53-58, 2021 02 01.
Article in English | MEDLINE | ID: covidwho-990853

ABSTRACT

PURPOSE OF REVIEW: The present review summarizes recent original publications addressing the topic of risk-adapted adjuvant therapy in early breast cancer (EBC). As neoadjuvant therapy has become a standard for triple negative and HER2+ EBC, it focusses on luminal EBC. RECENT FINDINGS: Gene expression assays have become standard of care in luminal EBC, at least for patients with node negative disease. Two prospective randomized clinical trials, TAILORx (Oncotype DX) and MINDACT (MammaPrint) have presented additional analyses underlining the clinical utility of the tests. In times of COVID-19, immunohistochemically determined ER, PR, and Ki67 and early Ki67 response to endocrine therapy can be used to safely allocate patients for preoperative endocrine therapy and delay surgeries if resources are scarce. In patients with luminal high-risk disease, adding a CDK 4/6 inhibitor (abemaciclib) improves patient outcome already after short-term follow-up. SUMMARY: Determination of recurrence risk will remain important in luminal EBC for optimal therapy decisions. In the future, risk-adapted treatment concepts will include decision making for chemotherapy but also for endocrine-based approaches.


Subject(s)
Antineoplastic Agents, Hormonal/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , COVID-19/epidemiology , Protein Kinase Inhibitors/therapeutic use , Aminopyridines/therapeutic use , Benzimidazoles/therapeutic use , Breast Neoplasms/pathology , Breast Neoplasms/surgery , Female , Gene Expression Profiling , Humans , Ki-67 Antigen/metabolism , Neoadjuvant Therapy , Piperazines/therapeutic use , Pyridines/therapeutic use , Receptor, ErbB-2/genetics , Receptor, ErbB-2/metabolism , Receptors, Estrogen/genetics , Receptors, Estrogen/metabolism , Receptors, Progesterone/genetics , Receptors, Progesterone/metabolism , Risk Assessment , SARS-CoV-2
14.
Expert Rev Mol Diagn ; 21(1): 101-107, 2021 01.
Article in English | MEDLINE | ID: covidwho-962282

ABSTRACT

Background: The SARS-CoV-2 pandemic introduced a global distraction effect in cancer patients' care. The aim of this study was to explore the effect of the pandemic on the largest molecular diagnostics center for cancer patients and high-risk individuals in Serbia.Research design and methods: EGFR, KRAS/NRAS, BRAF, and BRCA1/2 mutation testing were performed by qPCR and NGS. NGS was used for panel testing of hereditary breast/ovarian cancer and cancers associated with Lynch syndrome. The analytical output during the state of emergency (SoE) was compared to the period before and after the outbreak using one-way ANOVA. Statistical significance was set at p < 0.05.Results: A 38% reduction in the number of analysis was detected during the SoE. After the SoE, a 19% reduction was noted compared to SoE and 50% compared to the period before the SoE (p = 0.038). Three of the 48 scheduled appointments for pretest genetic counseling were carried out during the SoE, but the number of NGS tests increased by 50%.Conclusions: The SARS-CoV-2 pandemic had a profound negative effect on the diagnostic output of our centralized molecular diagnostics center. The only positive effect was shortening of waiting lists for hereditary cancer patients and high-risk individuals.


Subject(s)
Breast Neoplasms/diagnosis , Colorectal Neoplasms, Hereditary Nonpolyposis/diagnosis , Mutation , Ovarian Neoplasms/diagnosis , BRCA1 Protein/genetics , BRCA2 Protein/genetics , Breast Neoplasms/genetics , COVID-19 , Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , DNA Mutational Analysis , ErbB Receptors/genetics , Female , GTP Phosphohydrolases/genetics , Genetic Counseling , Genetic Predisposition to Disease , Humans , Liquid Biopsy , Membrane Proteins/genetics , Ovarian Neoplasms/genetics , Pandemics , Pathology, Molecular , Pharmacogenetics , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins p21(ras)/genetics , Serbia/epidemiology
15.
Eur J Med Genet ; 63(12): 104098, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-917288

ABSTRACT

INTRODUCTION: Mainstreamed genetic testing (MGT) obviates the need for a cancer genetics consultation, since trained oncologists (O) and gynaecologists (G) provide counseling, prescribe testing and deliver results. We report results from our MGT program and emphasize its utility during the COVID-19 lockdown, when cancer genetics clinics had suspended their activity. METHODS: An MGT pathway for breast and ovarian cancer (BC/OC) patients was established in Jan-2018 between the Assistance Publique - Hôpitaux de Paris.Sorbonne Université Cancer Genetics team and the Oncology/Gynecology departments at one teaching and two regional hospitals. Trained O + G evaluated patients with the Manchester Scoring System. A 12-point threshold was recommended for testing. Next-generation sequencing of BRCA1, BRCA2, PALB2, RAD51C and RAD51D was performed. Results were delivered to the patient by O/G. Pathogenic variants (PV) carriers were referred to the genetics clinic. Results are reported for the 2nd-Jan-2018 to 1st-June-2020 period. That includes the eight-week COVID-19 lockdown and three-week de-confinement phase 1. RESULTS: Results were available for 231/234 patients. Twenty-eight (12.1%) carried a PV. Of the 27 patients tested during the COVID-19 period, three carried a PV, two in BRCA1 and one in RAD51C. The clinical impact was immediate for the two BRCA1 BC cases undergoing neo-adjuvant chemotherapy, since double mastectomy and salpingo-oophorectomy will now be performed using two-step strategies. CONCLUSIONS: MGT guaranteed care continuity in BC/OC patients during the critical phases of the COVID-19 pandemic, with immediate implications for PV carriers. More broadly, we report for the first time the successful implementation of MGT in France.


Subject(s)
Breast Neoplasms/genetics , COVID-19/epidemiology , Genetic Testing , Hereditary Breast and Ovarian Cancer Syndrome/genetics , Ovarian Neoplasms/genetics , Pandemics , Adult , Aged , Aged, 80 and over , BRCA1 Protein/genetics , BRCA2 Protein/genetics , Breast Neoplasms/drug therapy , Breast Neoplasms/surgery , DNA-Binding Proteins/genetics , Fanconi Anemia Complementation Group N Protein/genetics , Female , Genetic Counseling , Genetic Predisposition to Disease , High-Throughput Nucleotide Sequencing , Humans , Male , Mastectomy , Middle Aged , Neoadjuvant Therapy , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/surgery , Paris/epidemiology , Salpingo-oophorectomy , Young Adult
16.
Indian J Pathol Microbiol ; 63(2): 169-170, 2020.
Article in English | MEDLINE | ID: covidwho-820105
17.
Breast Cancer Res Treat ; 184(2): 637-647, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-716322

ABSTRACT

PURPOSE: The COVID-19 pandemic has impacted early breast cancer (EBC) treatment worldwide. This study analyzed how Brazilian breast specialists are managing EBC. METHODS: An electronic survey was conducted with members of the Brazilian Society of Breast Cancer Specialists (SBM) between April 30 and May 11, 2020. Bivariate analysis was used to describe changes in how specialists managed EBC at the beginning and during the pandemic, according to breast cancer subtype and oncoplastic surgery. RESULTS: The response rate was 34.4% (503/1462 specialists). Most of the respondents (324; 64.4%) lived in a state capital city, were board-certified as breast specialists (395; 78.5%) and either worked in an academic institute or one associated with breast cancer treatment (390; 77.5%). The best response rate was from the southeast of the country (240; 47.7%) followed by the northeast (128; 25.4%). At the beginning of the pandemic, 43% changed their management approach. As the outbreak progressed, this proportion increased to 69.8% (p < 0.001). The southeast of the country (p = 0.005) and the state capital cities (p < 0.001) were associated with changes at the beginning of the pandemic, while being female (p = 0.001) was associated with changes during the pandemic. For hormone receptor-positive tumors with the best prognosis (Ki-67 < 20%), 47.9% and 17.7% of specialists would recommend neoadjuvant endocrine therapy for postmenopausal and premenopausal women, respectively. For tumors with poorer prognosis (Ki-67 > 30%), 34% and 10.9% would recommend it for postmenopausal and premenopausal women, respectively. Menopausal status significantly affected whether the specialists changed their approach (p < 0.00001). For tumors ≥ 1.0 cm, 42.9% of respondents would recommend neoadjuvant systemic therapy for triple-negative tumors and 39.6% for HER2 + tumors. Overall, 63.4% would recommend immediate total breast reconstruction, while only 3.4% would recommend autologous reconstruction. In breast-conserving surgery, 75% would recommend partial breast reconstruction; however, 54.1% would contraindicate mammoplasty. Furthermore, 84.9% of respondents would not recommend prophylactic mastectomy in cases of BRCA mutation. CONCLUSIONS: Important changes occurred in EBC treatment, particularly for hormone receptor-positive tumors, as the outbreak progressed in each region. Systematic monitoring could assure appropriate breast cancer treatment, mitigating the impact of the pandemic.


Subject(s)
Antineoplastic Agents, Hormonal/therapeutic use , Antineoplastic Agents/therapeutic use , Breast Neoplasms/therapy , Coronavirus Infections , Mammaplasty , Mastectomy , Neoadjuvant Therapy , Pandemics , Pneumonia, Viral , Adult , Betacoronavirus , Brazil , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , COVID-19 , Delivery of Health Care , Disease Management , Female , Genes, BRCA1 , Genes, BRCA2 , Humans , Male , Mastectomy, Segmental , Middle Aged , Patient Selection , Postmenopause , Premenopause , Prophylactic Mastectomy , Receptor, ErbB-2/metabolism , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , SARS-CoV-2 , Societies, Medical , Surveys and Questionnaires , Tumor Burden
18.
Cancer ; 126(20): 4466-4472, 2020 10 15.
Article in English | MEDLINE | ID: covidwho-693298

ABSTRACT

BACKGROUND: The objective of the current study was to provide insight into the effect of coronavirus disease 2019 (COVID-19) on breast cancer screening, breast surgery, and genetics consultations. METHODS: User data from a risk assessment company were collected from February 2 to April 11, 2020. The use of risk assessment was used as a proxy for the use of 3 breast cancer services, namely, breast imaging, breast surgery, and genetics consultation. Changes in the use of these services during the study period were analyzed. RESULTS: All 3 services experienced significant declines after the COVID-19 outbreak. The decline in breast surgery began during the week of March 8, followed by breast imaging and genetics consultation (both of which began during the week of March 15). Breast imaging experienced the most significant reduction, with an average weekly decline of 61.7% and a maximum decline of 94.6%. Breast surgery demonstrated an average weekly decline of 20.5%. When surgical consultation was stratified as breast cancer versus no breast cancer, the decrease among in non-breast cancer patients was more significant than that of patients with breast cancer (a decline of 66.8% vs 11.5% from the pre-COVID average weekly volume for non-breast cancer patients and patients with breast cancer, respectively). During the week of April 5, use of genetics consultations dropped to 39.9% of the average weekly volumes before COVID-19. CONCLUSIONS: COVID-19 has had a significant impact on the number of patients undergoing breast cancer prevention, screening, diagnosis, and treatment.


Subject(s)
Breast Neoplasms/diagnostic imaging , Breast Neoplasms/genetics , Breast Neoplasms/surgery , COVID-19 , Mastectomy/statistics & numerical data , Breast Neoplasms/prevention & control , Female , Genetic Counseling/statistics & numerical data , Humans , Mammography/statistics & numerical data , Risk Assessment , United States/epidemiology
20.
Mol Biol Rep ; 47(6): 4857-4860, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-209514

ABSTRACT

The first person-to-person transmission of the 2019-novel coronavirus in Italy on 21 February 2020 led to an infection chain that represents one of the largest known COVID-19 outbreaks outside Asia. Hospitals have been forced to reorganized their units in response to prepare for an unforeseen healthcare emergency. In this context, our laboratory (Molecular and Genomic Diagnostics Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS) re-modulated its priorities by temporarily interrupting most of the molecular tests guaranteeing only those considered "urgent" and not postponable. In particular, this paper details changes regarding the execution of germline BRCA (gBRCA) testing in our laboratory. A substantial reduction in gBRCA testing (about 60%) compared to the first 2 months of the current year was registered, but the requests have not been reset. The requesting physicians were mainly gynaecologists and oncologists. These evidences further emphasize the new era of gBRCA testing in the management of cancer patients and confirms definitively the integration of gBRCA testing/Next Generation Sequencing (NGS) into clinical oncology. Finally, a re-organization of gBRCA testing in our Unit, mainly related to delayed and reduced arrival of tests was necessary, ensuring, however, a high-quality standard and reliability, mandatory for gBRCA testing in a clinical setting.


Subject(s)
BRCA2 Protein/genetics , Breast Neoplasms/diagnosis , Coronavirus Infections/epidemiology , Early Detection of Cancer/statistics & numerical data , Ovarian Neoplasms/diagnosis , Pandemics , Pneumonia, Viral/epidemiology , Betacoronavirus/genetics , Betacoronavirus/pathogenicity , Biomarkers, Tumor/genetics , Breast Neoplasms/genetics , Breast Neoplasms/pathology , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques/statistics & numerical data , Coronavirus Infections/blood , Coronavirus Infections/diagnosis , Coronavirus Infections/pathology , Early Detection of Cancer/methods , Early Diagnosis , Female , Genomics/methods , High-Throughput Nucleotide Sequencing/statistics & numerical data , Humans , Italy/epidemiology , Mutation , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , Pneumonia, Viral/blood , Pneumonia, Viral/diagnosis , Pneumonia, Viral/pathology , Referral and Consultation/statistics & numerical data , SARS-CoV-2
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