11 results on '"Kadouri L"'
Search Results
2. BRCA1/2 mutation carriers vs the general breast cancer population (N = 799,986): 21-gene assay-based molecular characterization.
- Author
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Yerushalmi R, Pomerantz A, Lewin R, Paluch-Shimon S, Soussan-Gutman L, Baehner FL, Voet H, Bareket-Samish A, Kedar I, Goldberg Y, Peretz-Yablonski T, and Kadouri L
- Subjects
- Humans, Female, Middle Aged, Aged, Retrospective Studies, Biomarkers, Tumor genetics, Germ-Line Mutation, Mutation, Heterozygote, Adult, Genetic Predisposition to Disease, Breast Neoplasms genetics, Breast Neoplasms pathology, BRCA2 Protein genetics, BRCA1 Protein genetics
- Abstract
Purpose: We compared 21-gene recurrence score (RS) distribution and expression of the single-gene/gene groups within this assay between BC patients with pathogenic variants (PV) in BRCA1/2 vs the general 21-gene-tested BC population., Methods: This retrospective study included consecutive 21-gene-tested female ER + HER2-negative BC patients with germline PVs in BRCA1/2. RS/gene expression data were compared to a previously described commercial use database (CDB, N = 799,986). Chi-square and 1-sample t test were used to compare RS distribution and single-gene/gene group scores between the study group and the CDB., Results: Study group patients (N = 81) were younger and their RS results were higher compared to the CDB (age: median [IQR], 56 [47-61.5] vs 60 [51-67] years; p < 0.001; proportion of patients with RS ≥ 26: 49.4% vs 16.4%, p < 0.001). Expression of 12/16 cancer genes in the assay and the ER, proliferation, and invasion gene group scores differed significantly between the study group and the CDB, all in a direction contributing to higher RS. The differences between the study group and the CDB were mostly retained, upon stratifying the patients by menopausal status., Conclusion: BC patients with PVs in BRCA1/2 have higher RS results that stem from distinct gene expression profiles in the majority of genes in the 21-gene assay., (© 2024. The Author(s).)
- Published
- 2024
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3. Clinical and genetic characteristics of carriers of the TP53 c.541C > T, p.Arg181Cys pathogenic variant causing hereditary cancer in patients of Arab-Muslim descent.
- Author
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Arnon J, Zick A, Maoz M, Salaymeh N, Gugenheim A, Marouani M, Mor E, Hamburger T, Saadi N, Elia A, Ganz G, Fahham D, Meirovitz A, Kadouri L, Meiner V, Yablonski-Peretz T, and Shkedi-Rafid S
- Abstract
TP53 pathogenic variants cause Li-Fraumeni syndrome (LFS), with some variants causing an attenuated phenotype. Herein, we describe the clinical phenotype and genetic characteristics of carriers of NM_000546.6 (TP53): c.541C > T, (p.Arg181Cys) treated at Hadassah Medical Center. We retrospectively examined our genetic databases to identify all carriers of TP53 p.Arg181Cys. We reached out to carriers and their relatives and collected clinical and demographic data, lifestyle factors, carcinogenic exposures as well as additional blood samples for genetic testing and whole exome sequencing. Between 2005 and 2022 a total of 2875 cancer patients underwent genetic testing using genetic panels, whole exome sequencing or targeted TP53 assays. A total of 30 cancer patients, all of Arab-Muslim descent, were found to be carriers of TP53 p.Arg181Cys, the majority from Jerusalem and Hebron, two of which were homozygous for the variant. Carriers were from 24 distinct families of them, 15 families (62.5%) met updated Chompret criteria for LFS. Median age of diagnosis was 35 years-old (range 1-69) with cancers characteristic of LFS (16 Breast cancer; 6 primary CNS tumors; 3 sarcomas) including 4 children with choroid plexus carcinoma, medulloblastoma, or glioblastoma. A total of 21 healthy carriers of TP53 p.Arg181Cys were identified at a median age of 39 years-old (range 2-54)-19 relatives and 2 additional pediatric non-cancer patients, in which the finding was incidental. We report a shared haplotype of 350kb among carriers, limited co-morbidities and low BMI in both cancer patients and healthy carriers. There were no demographic factors or carcinogenic exposures unique to carriers who developed malignancy. Upon exome analysis no other known pathogenic variants in cancer predisposing genes were identified. TP53 p.Arg181Cys is a founder pathogenic variant predominant to the Arab-Muslim population in Jerusalem and Hebron, causing attenuated-LFS. We suggest strict surveillance in established carriers and encourage referral to genetic testing for all cancer patients of Arab-Muslim descent in this region with LFS-associated malignancies as well as family members of established carriers., (© 2024. The Author(s).)
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- 2024
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4. MRI prediction of neoadjuvant chemotherapy response is equivalent in patients with or without mammographic calcifications: a step towards adapting surgical approach?
- Author
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Sella T, Simor B, Adler-Levy Y, Maly B, Kadouri L, and Carmon E
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- Humans, Female, Neoadjuvant Therapy methods, Retrospective Studies, Prospective Studies, Mammography methods, Magnetic Resonance Imaging methods, Neoplasm, Residual pathology, Chemotherapy, Adjuvant, Breast Neoplasms diagnostic imaging, Breast Neoplasms drug therapy, Breast Neoplasms surgery, Calcinosis diagnostic imaging, Calcinosis pathology
- Abstract
Objectives: Current surgical policy recommends comprehensive excision of tumorous calcifications in breast cancer patients following neoadjuvant chemotherapy (NAC) regardless of MRI outcomes, despite MRI defining tumor response superior to mammography. The current study examines MRI prediction of response in tumors with vs without calcifications, using post-NAC surgical pathology as the standard of reference., Methods: Retrospective analysis of 114 NAC patients between 2011 and 2018 including demographics, mammography, 3 T-MRI, and pathology compared two sub-groups: without (n = 62) or with (n = 52) mammographic calcifications. In the calcification cohort, the mammographic extent of calcifications and MRI enhancement overlapped. MRI prediction of response to NAC was correlated with pathology. Two-tailed paired T and Fisher's exact tests and Cohen's kappa coefficient were applied for analysis., Results: There was no significant difference between the two sub-groups regarding demographics. Tumors demonstrated equivalent features regarding size, lymph node involvement, and DCIS component. ER-negative/HER2-positive tumors more commonly exhibited calcifications (33% n = 17 calcified vs 13% n = 8 non-calcified; p < 0.05); triple negative pathology rarely calcified (6% n = 3 calcified vs 33% n = 20 non-calcified; p < 0.05). NME was more common with calcifications (62% n = 32 calcified vs 29% n = 18 non-calcified; p < 0.05) and mass enhancement without (90% n = 56 non-calcified vs 81% n = 42 calcified; p < 0.05). Both groups responded similarly to NAC (pCR = 37% non-calcified vs 38% calcified); response on MRI equally correlated with pathology (69% both subgroups; p = 0.988)., Conclusion: We propose utilizing post-NAC MRI findings rather than mammography in planning surgery, as MRI prediction is independent of the presence or absence of calcifications. Prospective studies to evaluate this approach are warranted., Key Points: • No difference was found in demographic, clinical, pathology, or imaging characteristics between patients with or without tumoral calcifications on mammography prior to neoadjuvant chemotherapy. • Residual mammographic calcifications are inadequate predictors of residual invasive disease. MRI accurately recognized complete response and correctly correlated with post-treatment surgical pathology in 69% of patients, regardless of the presence or absence of mammographic calcifications. • We propose utilizing post-NAC MRI findings rather than mammography in planning post-NAC surgery, as MRI prediction of response is independent of the presence or absence of calcifications., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)
- Published
- 2023
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5. Clinical Characteristics, Response to Platinum-Based Chemotherapy and Poly (Adenosine Phosphate-Ribose) Polymerase Inhibitors in Advanced Lung Cancer Patients Harboring BRCA Mutations.
- Author
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Arnon J, Tabi M, Rottenberg Y, Zick A, Blumenfeld P, Hamburger T, Pikarsky E, Avraham E, Levine L, Popovtzer A, Yablonski-Peretz T, Kadouri L, and Nechushtan H
- Abstract
The oncogenic role and clinical relevance of BRCA mutations in NSCLC remain unclear. We aim to evaluate the characteristics and clinical outcomes of patients with NSCLC harboring BRCA mutations treated at Hadassah Medical Center (HMC). We retrospectively assessed all patients with advanced NSCLC who underwent next-generation sequencing (NGS) and were found to have pathogenic somatic BRCA mutations (p-BRCA). We compared clinical outcomes in NSCLC patients with wild-type BRCA (wt-BRCA) matched by age, stage, gender, smoking, PDL-1 and driver mutations. Between 2015 and 2022, we evaluated 598 patients with advanced NSCLC using NGS and found 26 patients with p-BRCA, of whom 17 (65.4%) were carriers of germline BRCA variants and represented 1% of all BRCA carriers HMC. The median age of diagnosis was 67 years old (40-78), 13 patients (50%) had a history of smoking and 9 patients (34.6%) had additional driver mutations (EGFR, ALK, BRAF, MET or ERBB2). Objective response rate and median progression-free survival (PFS) for first-line platinum-based chemotherapy in the p-BRCA group compared to wt-BRCA controls were 72.2% and 16 months (CI 95%, 5-22), compared to 47.4% and 7 months (CI 95%, 5-9), respectively, and HR for PFS was 0.41 (CI 95%, 0.17-0.97). Six patients in the p-BRCA group were treated with advanced-line poly (adenosine-phosphate-ribose) polymerase inhibitors (PARPi), with a durable response observed in four patients (66%). In this cohort, patients with NSCLC harboring p-BRCA exhibit high-sensitivity PARPi and a prolonged response to platinum, suggesting some oncogenic role for BRCA mutations in NSCLC. The results support further prospective trials of the treatment of NSCLC harboring p-BRCA with PARPi.
- Published
- 2023
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6. Breast Cancer with Low Recurrence Score on Oncotype DX © : Interplay Between Early Recurrence, Lobular Histology and BRCA Mutation.
- Author
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Zarbiv Y, Wygoda YB, Grinshpun A, Hamburger T, Sella T, Breuer S, Maimon O, Rottenberg Y, Peretz T, and Kadouri L
- Abstract
Introduction: The 21-gene recurrence score assay Oncotype DX
© (ODX) has clear prognostic and predictive value regarding adjuvant chemotherapy. However, recent studies have shown the clinical distinctiveness of both BRCA1/2-driven early breast cancer (EBC) and invasive lobular (ILC) breast cancers. We evaluated the association between BRCA1/2-driven EBC/ILC and Oncotype DX failure despite a recurrence score ≤ 20., Methods: Here, we describe a small cohort of 16 patients from our center who, despite a low recurrence score (RS) ≤ 20, suffered from early disease recurrence. Clinical parameters of our cohort of patients were compared to a cohort from the general population of Clalit Health Service (CHS)., Results: Median age at diagnosis in our cohort was significantly younger. BRCA mutational status was available in 14 patients in our cohort. A high percentage of these patients had BRCA1/2 mutations (35.7%), either germline (in 3) or somatic (in 2). Half of our cohort was diagnosed with lobular carcinoma (ILC) relative to 10-15% in the general population of BC (p = 0.02). The median time to recurrence was 44 months., Conclusion: BRCA1/2 mutation and ILC are highly represented in this cohort. Although our cohort is small, these data may suggest that a RS ≤ 20 in these subgroups may not reflect a low risk of recurrence., (© 2022. The Author(s).)- Published
- 2022
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7. Genetic anticipation of breast cancer among BRCA1/BRCA2 mutation carriers: A retrospective study.
- Author
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Kedmi A, Kadouri L, Sagy I, Hamburger T, Levin G, Zimhony-Nissim N, and Peretz T
- Subjects
- Anticipation, Genetic, BRCA1 Protein genetics, BRCA2 Protein genetics, Female, Heterozygote, Humans, Mutation, Retrospective Studies, Breast Neoplasms genetics, Breast Neoplasms pathology, Genes, BRCA2
- Abstract
Objective: To study the anticipation phenomenon among hereditary breast cancer patients, by evaluating trends in age at diagnosis and phenotype of breast cancer across two successive generation pairs of BRCA1/2 mutation carriers/non-carriers with breast cancer after reports of an earlier age of diagnosis in successive generations among BRCA1/2 mutation carrier families., Method: A retrospective cohort study. Patient characteristics, pathologic data and survival were compared between mothers and daughters and between carriers and non-carriers., Results: Overall, 126 patients were found, who formed 67 pairs of mothers and daughters diagnosed with breast cancer and genetically tested for BRCA mutations. Age at diagnosis was significantly younger in the daughter versus mother generation, in both groups of BRCA carriers/non-carriers. Tumor characteristics were not different between mothers and daughters. Survival analysis revealed a not significant better outcome for the daughter generation versus the mother generation., Conclusions: Breast cancer appeared to be diagnosed at an earlier age in successive generations among BRCA mutation carriers and non-carriers. The fact that we also observed a downshift at age of diagnosis in non-carrier pairs emphasizes that other factors (environmental, lifestyle, or social) may influence the age at diagnosis., (© 2022 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)
- Published
- 2022
- Full Text
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8. Preoperative MRI for Evaluation of Extent of Disease in IDC Compared to ILC.
- Author
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Carmon E, Alster T, Maly B, Kadouri L, Kleinman TA, and Sella T
- Subjects
- Female, Humans, Magnetic Resonance Imaging methods, Retrospective Studies, Breast Neoplasms diagnostic imaging, Breast Neoplasms pathology, Breast Neoplasms surgery, Carcinoma, Ductal, Breast pathology, Carcinoma, Lobular diagnostic imaging, Carcinoma, Lobular pathology, Carcinoma, Lobular surgery
- Abstract
Objectives: The purpose of this study was to assess the incremental value of preoperative breast MRI over mammography and US in depicting the accurate extent of disease in invasive duct carcinoma (IDC) compared to invasive lobular carcinoma (ILC)., Patients and Methods: Retrospective analysis of pre-operative mammography, US and MRI was performed in 239 patients with either IDC (n = 193) or ILC (n = 46). Images were evaluated for solitary, multifocal or multi centric disease and compared for concordance with postsurgical pathology. Discordance was documented as either overestimation or underestimation. Two tailed paired T and Fischer's exact tests were used for analysis., Results: Multifocality was present on pathology in 35% and 61% of patients with IDC and ILC (P < .05) and multicentricity in 23% and 41% respectively (P = .84). In ILC, MRI demonstrated better concordance with pathology compared to mammography and US (89%, 44%, 49% for multifocality [P < .05] and 80.5%, 63%, 71% for multicentricity [P = .3]). For IDC, concordance with pathology for all modalities was similar (65%-76%). Among discordant cases, underestimation was significantly more common for mammography and US, while MRI more frequently overestimated disease extent. MRI very rarely overestimated multifocal disease in ILC (2%)., Conclusion: MRI demonstrates an 80% to 90% concordance rate with pathology for ILC, superior to mammography and US. The addition of MRI in IDC patients may decrease underestimation of disease extent and potentially contribute to a reduction in post-operative residual disease., (Copyright © 2022. Published by Elsevier Inc.)
- Published
- 2022
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9. Potential Refinement of Recurrence Score by pSTAT3 Status.
- Author
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Grinshpun A, Cohen Y, Zick A, Kadouri L, Hamburger T, Nisman B, Allweis TM, Oprea G, Peretz T, Uziely B, and Sonnenblick A
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- Biomarkers, Tumor genetics, Female, Humans, Prognosis, Breast Neoplasms pathology, Neoplasm Recurrence, Local genetics, Neoplasm Recurrence, Local pathology
- Abstract
The likelihood of recurrence in breast cancer patients with hormone receptor-positive (HR-positive) tumors is influenced by clinical, histopathological, and molecular features. Recent studies suggested that activated STAT3 (pSTAT3) might serve as a biomarker of outcome in breast cancer patients. In the present work, we have analyzed the added value of pSTAT3 to OncotypeDx Recurrence Score (RS) in patient prognostication. We have found that patients with low RS (<26) and low pSTAT3 might represent a population at a higher risk for cancer recurrence. Furthermore, we have observed that a positive pSTAT3 score alone can be a favorable marker for patients with HR-positive breast cancer under the age of 50. In an era of personalized medicine, these findings warrant further appraisal of chemotherapy benefit in this population.
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- 2022
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10. Assessment of Response to a Third Dose of the SARS-CoV-2 BNT162b2 mRNA Vaccine in Patients With Solid Tumors Undergoing Active Treatment.
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Rottenberg Y, Grinshpun A, Ben-Dov IZ, Oiknine Djian E, Wolf DG, and Kadouri L
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- BNT162 Vaccine, Humans, SARS-CoV-2, Vaccines, Synthetic, mRNA Vaccines, COVID-19, Neoplasms drug therapy
- Published
- 2022
- Full Text
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11. Thyroid Hormones and Morphological Features of Primary Breast Cancer.
- Author
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Meirovitz A, Nisman B, Allweis TM, Carmon E, Kadouri L, Maly B, Maimon O, and Peretz T
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- Adult, Aged, Biomarkers, Tumor blood, Breast Neoplasms pathology, Carcinoma in Situ pathology, Cell Proliferation genetics, Female, Humans, Middle Aged, Neoplasm Invasiveness genetics, Neoplasm Invasiveness pathology, Neoplasm Recurrence, Local pathology, Prognosis, Thymidine Kinase blood, Thyroid Function Tests, Thyroid Gland pathology, Thyroid Hormones genetics, Thyrotropin blood, Thyroxine blood, Triiodothyronine blood, Breast Neoplasms blood, Carcinoma in Situ blood, Neoplasm Recurrence, Local blood, Thyroid Gland metabolism, Thyroid Hormones blood
- Abstract
Background/aim: Many experimental studies have suggested the importance of thyroid hormones in breast cancer (BC) morphogenesis. The aim of this study was to evaluate the association of thyroid hormone levels in serum of patients with primary BC with morphological presentations of the disease in pathological specimens and prognosis., Patients and Methods: We measured the serum levels of thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4), along with serum thymidine kinase 1 activity and examined their relation to pathological features and prognosis of 158 patients with primary BC., Results: We found a significant positive association of serum FT3 level with the presence of carcinoma in situ component (CIS) (p=0.032) and its size (p=0.047), with the presence (p=0.022) and the number of multifocal/multicentric tumors (MMTs) (p=0.002), as well as with increased proliferative activity in terms of serum thymidine kinase 1 (p=0.002). Moreover, we report that each 1.0 unit rise of FT3/FT4 ratio×10 was associated with an odds ratio of 1.77 (95% confidence interval=1.17-3.30, p=0.007), 1.97 (95% confidence interval=1.17-2.67, p=0.010) and 1.56 (95% confidence interval=1.02-2.37, p=0.039) for the detection of patients with CIS, MMTs and lymphovascular invasion, respectively, after adjusting for age. We did not find statistically significant associations of serum TSH level with breast cancer`s parameters. A Cox regression survival analysis identified serum FT3 level >5.95 pmol/l as a risk factor for BC recurrence (relative risk=2.65, p=0.017), a finding that retained significance in a multivariate model (relative risk=2.52, p=0.027)., Conclusion: The FT3/FT4 ratio is a valuable parameter predicting the presence of CIS, MMTs and lymphovascular invasion in pathological specimens. An elevated serum FT3 level is associated with the presence of CIS, MMTs, increased proliferative activity and poor prognosis., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
- Published
- 2022
- Full Text
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