87 results on '"Gebrim LH"'
Search Results
2. Pyoderma Gangrenosum: Report of a Case Involving the Breast
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Amorim AG, Ramos MNM, Cavagna FA, Sawada MIBAC, Melitto AS, Mazzarone G, Mattar A, Shida JY, and Gebrim LH
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- 2018
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3. Abstract P6-05-15: Analysis of Ki-67 index on normal breast tissue of premenopausal women exposed to tamoxifen and raloxifene: A randomized, double-blind study
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Da Silva, BB, primary, Lopes-Costa, PV, additional, Rosal, MA, additional, and Gebrim, LH, additional
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- 2013
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4. Abstract P5-09-15: Polymorphism of the CYP2D6 gene in Brazilian women with breast cancer treated with tamoxifen
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da Silva, BB, primary, de Vasconcelos-Valença, RJ, additional, Lopes-Costa, PV, additional, and Gebrim, LH, additional
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- 2013
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5. Abstract P2-05-17: Correlation between cyclin D1, estrogen and progesterone receptors in invasive breast cancer after short-term treatment with tamoxifen or anastrozole
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Millen, EC, primary, Mattar, A, additional, Logullo, AF, additional, Nonogaki, S, additional, Soares, FA, additional, and Gebrim, LH, additional
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- 2012
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6. P5-07-06: Effect of Angiotensin-(1-7) and Angiotensin II on T47D Breast Cancer Cells in the Proliferation and cAMP Production.
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da, Silva IDCG, primary, Correa-Noronha, SSAA, additional, Noronha, SMR, additional, Alecrim, C, additional, Shimuta, SI, additional, Nakaie, CR, additional, Gebrim, LH, additional, and Nazario, ACP, additional
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- 2011
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7. P3-07-37: Clinical Characteristics and Treatment of Brazilian Women with Breast Cancer at Public and Private Institutions.
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Hegg, R, primary, Mattar, A, additional, Gebrim, LH, additional, Emerenciano, K, additional, Pinotti, M, additional, Perdicaris, M, additional, van, Eyll B, additional, Franke, F, additional, Pinczowski, H, additional, Freitas, R, additional, Jendiroba, D, additional, Borges, G, additional, Queiroz, G, additional, Nascimento, YV, additional, Gampel, O, additional, Mathias, C, additional, Budel, V, additional, Strepassos, E, additional, and Delgado, G, additional
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- 2011
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8. Abstract P2-06-05: p27 Expression in Hormone Sensitive Breast Carcinomas, Prior and after Short Term Hormone Treatment: A Prospective Placebo Double-Blind Study
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Portela, RMO, primary, Mattar, A, additional, Waitzberg, ÂFL, additional, Shida, JY, additional, Soares, FA, additional, Nonogaki, S, additional, and Gebrim, LH., additional
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- 2010
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9. Abstract P2-06-07: Estrogen Receptor Beta as a Coadjuvant Target? A Short-Time Prospective Double Blind Study
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Madeira, M, primary, Mattar, A, additional, Joo, YK, additional, Cintra, KA, additional, Logullo, AF, additional, Soares, FA, additional, Nonogaki, S, additional, and Gebrim, LH., additional
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- 2010
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10. PCN62 COST ANALYSIS OF HORMONE RECEPTOR POSITIVE, ADVANCED BREAST CANCER TREATMENT WITH ENDOCRINE THERAPY VERSUS CHEMOTHERAPY IN THE BRAZILIAN PUBLIC HEALTH CARE SYSTEM (BPHS)
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Abdo Filho, E, primary, Takemoto, M, additional, Teich, VD, additional, Quintella, FF, additional, Fernandes, RA, additional, Passos, RBF, additional, Teich, N, additional, Silva, AP, additional, Marques, M, additional, Mottola Jr, J, additional, Gebrim, LH, additional, Picinini, SE, additional, and Sakano, M, additional
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- 2009
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11. Effects of short-time tamoxifen therapy on breast cancer apoptosis and cell cycle regulators.
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Madeira, M, primary, Millen, EC, additional, Vivian, F, additional, Logullo, [F, additional, and Gebrim, LH, additional
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- 2009
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12. Structure and process of nursing care for prevention of surgical site infection: observational study.
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da Silva LMG, Pawluk LC, Gebrim LH, Facina G, and de Gutiérrez MGR
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High rates of infection can reflect the quality of the service. Two previous studies in the same place reported an overall surgical site infection incidence of 14,1% and 22%, what motivated this research. The aim of this study was to analyze the structure and nursing process and its possible relationship with the prevention and control of surgical site infection (SSI). It is a descriptive, observational and documentary analysis study performed in a large general teaching Hospital in São Paulo from August 2007 to March 2008. The data were collected from institutional documents and trough directed observation of the nursing practice. The results showed that the normative documents are in accord with the current evidence. However, the structure issues present limitations with negative impact for the prevention of SSI. The nursing processes accomplished partially to the recommended standards, the hand washing, appropriate use of antibiotics and accomplishment of postoperative dressing's present improvement opportunities that could positively impact the surgical site infection's rates. These results point out the need of review the nursing process and the adequacy of some structural issues in order to achieve the standards for prevention and control of the surgical site infection. [ABSTRACT FROM AUTHOR]
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- 2009
13. RWD191 Real-World Ovarian Cancer Mortality Outcomes in a Brazilian Reference Women Healthcare Public Hospital.
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Mattar, A, Bernardino, G, Rodrigues, L, Alemar, M, Filho, RCS, Navarro, P, Arakelian, R, Piotto, G, de Almeida, MS, Gebrim, LH, and Tanaka, SY
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- 2024
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14. RWD149 Real-World Endometrial Cancer Mortality Outcomes at Brazilian Reference Women Healthcare Public Hospital.
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Mattar, A, Bernardino, G, Rodrigues, L, Alemar, M, Filho, RCS, Navarro, P, Arakelian, R, Piotto, G, de Almeida, MS, Gebrim, LH, and Tanaka, SY
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- 2024
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15. Real-world evidence of survival outcomes in breast cancer subtypes after neoadjuvant chemotherapy in a Brazilian reference center.
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Antonini M, Mattar A, Bauk Richter FG, Pannain GD, Teixeira MD, Amorim AG, da Costa Pinheiro DJP, Soares LR, Cavalcante FP, Moreira Ramos MDN, Madeira M, Zerwes F, Ferraro O, Lopes RGC, and Gebrim LH
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- Humans, Female, Middle Aged, Retrospective Studies, Brazil, Adult, Aged, Cohort Studies, Treatment Outcome, Breast Neoplasms drug therapy, Breast Neoplasms pathology, Breast Neoplasms mortality, Neoadjuvant Therapy methods
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Background: Neoadjuvant chemotherapy (NAC), traditionally used for locally advanced disease, is now applied for operable disease, particularly to treat aggressive breast cancer (BC). This study aimed to characterize the pathological complete response (pCR) and its relationship with overall survival (OS) and disease-free survival (DFS) among BC patients receiving NAC in a Brazilian public reference center, as well as the association between pCR and BC subtypes., Methods: A retrospective cohort study used a comprehensive BC database from a Brazilian women's health reference center, including patients diagnosed between 2011 and 2020 who underwent NAC. We collected demographic, cancer-specific, and treatment-related data, analyzing OS and DFS based on pCR status using the semiparametric Kaplan-Meier method, with the date of BC diagnosis as the starting point., Results: The study included 1,601 patients, with an average age of 49 years and a majority presenting stage IIIa disease (35%). Most had invasive nonspecial type (NST) BC (94%), and a significant portion (86.7%) exhibited a Ki-67 index <14. The overall pCR rate was 22.7%, with higher frequencies observed in the triple negative and luminal B subtypes. Patients who achieved pCR had significantly higher survival rates (89% alive vs. 61%, P<0.001) and better DFS (90% vs. 66%, P<0.001), except in the luminal A subtype, where pCR did not correlate with improved OS or DFS., Conclusions: These updated real-world data (RWD) from BC patients who underwent NAC in Brazil revealed a pCR rate of 22.7% in all cancer subtypes and stages. pCR was not associated with better outcomes in patients with luminal A, contrasting with other subtypes.
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- 2024
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16. Male and female disparities in breast cancer epidemiology: A comparative cross-sectional analysis of a Brazilian cohort (2017-2021).
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Antonini M, Mattar A, Pannain GD, Buttenbender SF, Pinheiro DJPDC, Teixeira MD, Amorim AG, Ferraro O, Lopes RGC, and Gebrim LH
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Male breast cancer (MBC) is a rare condition, accounting for approximately 1 % of all breast cancer cases. Nevertheless, the paucity of MBC-specific research has impeded a thorough understanding of MBC. In this study, we aimed to delineate the epidemiological implications of MBC in Brazil and benchmarked it against female breast cancer (FBC). This retrospective study analyzed data from the DATASUS database (2017-2021), which assessed the incidence of breast cancer in both sexes. All statistical analyses were performed using descriptive statistics and inferential methods, with significance set at a 95 % confidence interval. We identified 4,326 (1.7 %) and 233,793 (94.2 %) patients with MBC and FBC, respectively, in Brazil. Despite the general population concentration in the Southeast, MBC cases were more prevalent in the Northeast (p < 0.0004). At breast cancer diagnosis, males were typically older (mean age 59.5 [±10.2] years) than females (mean age 55.7 7 [±9.8] years). MBC was more commonly diagnosed clinically compared with FBC, which was most commonly diagnosed via screening. Surgical diagnostics were twice as likely in males, who also more frequently presented with advanced disease stages (stages III and IV; 72.8 % vs. 59.3 %), leading to a higher rate of mastectomy. Treatment was initiated earlier in males than in females. Although MBC comprises a minority of breast cancer cases, it is more frequently diagnosed at an advanced stage compared with FBC and necessitates aggressive treatment. Our study also underscores the potential benefit of prompt initiation of therapy and need for tailored clinical approaches in patients with MBC., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)
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- 2024
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17. Proteomic Profiling of HDL in Newly Diagnosed Breast Cancer Based on Tumor Molecular Classification and Clinical Stage of Disease.
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Santana MFM, Sawada MIBAC, Junior DRS, Giacaglia MB, Reis M, Xavier J, Côrrea-Giannella ML, Soriano FG, Gebrim LH, Ronsein GE, and Passarelli M
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- Humans, Female, Middle Aged, Adult, Aged, Lipoproteins, HDL blood, Lipoproteins, HDL metabolism, Aged, 80 and over, Proteome metabolism, Adolescent, Young Adult, Proteomics methods, Breast Neoplasms blood, Breast Neoplasms diagnosis, Breast Neoplasms classification, Breast Neoplasms metabolism, Breast Neoplasms genetics, Breast Neoplasms pathology, Neoplasm Staging
- Abstract
The association between high-density lipoprotein (HDL) cholesterol and breast cancer (BC) remains controversial due to the high complexity of the HDL particle and its functionality. The HDL proteome was determined in newly diagnosed BC classified according to the molecular type [luminal A or B (LA or LB), HER2, and triple-negative (TN)] and clinical stage of the disease. Women (n = 141) aged between 18 and 80 years with BC, treatment-naïve, and healthy women [n = 103; control group (CT)], matched by age and body mass index, were included. Data-independent acquisition (DIA) proteomics was performed in isolated HDL (D = 1.063-1.21 g/mL). Results: Paraoxonase1, carnosine dipeptidase1, immunoglobulin mMu heavy chain constant region (IGHM), apoA-4, and transthyretin were reduced, and serum amyloid A2 and tetranectin were higher in BC compared to CT. In TNBC, apoA-1, apoA-2, apoC-2, and apoC-4 were reduced compared to LA, LB, and HER2, and apoA-4 compared to LA and HER2. ComplementC3, lambda immunoglobulin2/3, serpin3, IGHM, complement9, alpha2 lysine rich-glycoprotein1, and complement4B were higher in TNBC in comparison to all other types; complement factor B and vitamin D-binding protein were in contrast to LA and HER2, and plasminogen compared to LA and LB. In grouped stages III + IV, tetranectin and alpha2-macroglobulin were reduced, and haptoglobin-related protein; lecithin cholesterol acyltransferase, serum amyloid A1, and IGHM were increased compared to stages I + II. Conclusions: A differential proteomic profile of HDL in BC based on tumor molecular classification and the clinical stage of the disease may contribute to a better understanding of the association of HDL with BC pathophysiology, treatment, and outcomes.
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- 2024
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18. Two Years Post-COVID-19: An Ecologic Study Evaluating the Impact on Brazil's Mammographic Screening Program.
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Antonini M, Mattar A, Pinheiro DJPDC, Teixeira MD, Amorim AG, Ferraro O, Cavalcante FP, Zerwes F, Madeira M, Millen EC, Frasson AL, Lopes RGC, Brenelli FP, Leite RM, Gebrim LH, and Freitas-Junior R
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- Humans, Female, Brazil epidemiology, Middle Aged, Aged, Retrospective Studies, SARS-CoV-2, Mass Screening methods, Mass Screening statistics & numerical data, Neoplasm Staging, Mammography statistics & numerical data, Mammography methods, COVID-19 epidemiology, COVID-19 diagnostic imaging, Breast Neoplasms diagnostic imaging, Breast Neoplasms epidemiology, Breast Neoplasms diagnosis, Early Detection of Cancer methods, Early Detection of Cancer statistics & numerical data
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Objectives: The objective of this study was to assess the impact of the COVID-19 pandemic, after 2 years, on mammographic screening in Brazil evaluating BIRADS® results, breast cancer diagnosis rates, and breast cancer stage., Study Design: This was an ecological observational study based on retrospective data from Brazil's mammographic screening program from 2015 to 2023., Methods: Data were obtained from the national screening database DATASUS - SISCAN (Cancer System Information) and retrieved in March 2024. Inclusion criteria comprised completeness of mammogram data (incomplete records were excluded), female participants aged 50 to 69 years, and mammograms exclusively performed for screening purposes. The study analyzed the number of mammograms conducted during the specified period, focusing on BIRADS® test results., Results: Out of 23,851,371 mammograms performed between 2015 and 2023, 15,000,628 were included for analysis. A significant reduction of 39.6% in mammograms was observed in 2020 compared to 2019, followed by a 12.6% decrease in 2021. Notably, a substantial rise in BIRADS categories 4 and 5 examinations was seen post-pandemic. Breast cancer staging analysis revealed a shift towards more advanced stages (III and IV) diagnosed post-pandemic, suggesting potential delays in detection and diagnosis., Conclusions: In conclusion, the study highlighted significant discrepancies in mammographic screenings and breast cancer diagnosis rates over 9 years. The pandemic reflected significant influence on the timing and stage at diagnosis, suggesting potential delays in detection and diagnosis that resulted in later identification of more advanced disease stages., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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- 2024
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19. Real-world evidence of neoadjuvant chemotherapy for breast cancer treatment in a Brazilian multicenter cohort: Correlation of pathological complete response with overall survival.
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Antonini M, Mattar A, Bauk Richter FG, Pannain GD, Teixeira MD, Amorim AG, Ferraro O, Guedes Lopes RC, Gebrim LH, and Real JM
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- Humans, Female, Adolescent, Adult, Brazil, Neoadjuvant Therapy, Retrospective Studies, Cohort Studies, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Prognosis, Trastuzumab therapeutic use, Disease-Free Survival, Breast Neoplasms pathology
- Abstract
Objectives: We aimed to evaluate the pCR rate in patients receiving NAC for the treatment of breast cancer (BC) in a multicenter cohort in Brazil. Additionally, we aimed to use RWD to assess the impact of pCR on OS and DFS., Methods: This was a retrospective, multicenter cohort study that included female patients over 18 years of age who were diagnosed with nonmetastatic breast cancer and received NAC. OS and DFS at five years were estimated by the Kaplan‒Meier method. Additionally, we conducted a multivariate analysis to identify factors that were significantly associated with pCR and OS., Results: From 2011 to 2020, 1891 patients were included in the study, and 421 (22,3%) achieved pCR (ypT0 ypN0). Considering the presence of residual DCIS, pCR was achieved in 467 patients (23,5%). The pCR rate varied between the subtypes: HER-2+ (p = 0,016) and clinical stage IIIA and IIIB (p < 0,001). Among HER-2+ patients, those who received trastuzumab had a significantly higher pCR rate than those who did not receive trastuzumab (p < 0.0001). Similarly, patients with TNBC who received treatment with platinum-based regimens also showed higher pCR rates (p < 0.0001). OS was grouped according to pCR status, and the OS rate was 88,3% in the pCR group and 58.1% in the non-pCR group (p < 0.0001). The five-year DFS was 92.2% in the pCR group and 64.3% in the non-pCR group (p < 0.0001)., Conclusion: The pCR rate and its prognostic value varied across BC subtypes. In our study, pCR could be used as a surrogate of favorable clinical outcome, as it was associated with higher OS and DFS rates., Competing Interests: Declaration of competing interest None., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2023
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20. Prognostic Factors and Survival Outcomes of Patients With Early HER2+ Breast Cancer Treated With Trastuzumab in a Brazilian Public Reference Center: A Real-World Study.
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Mattar A, Hegg R, Tayar DO, Rocha M, Terzian ALB, Oliveira RW, Julian GS, and Gebrim LH
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- Humans, Female, Trastuzumab, Prognosis, Retrospective Studies, Brazil epidemiology, Receptor, ErbB-2 therapeutic use, Disease-Free Survival, Neoadjuvant Therapy, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Chemotherapy, Adjuvant, Breast Neoplasms pathology
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Purpose: Trastuzumab was introduced into the Brazilian public health care service for early breast cancer (BC) in 2012. This study describes the survival outcomes and prognostic factors related to early HER2+ BC treatment in a Brazilian reference cancer center., Patients and Methods: This were a retrospective, single-center, observational study of early HER2+ BC patients treated with trastuzumab in the (neo)adjuvant setting between 2012 and 2018 at Hospital Pérola Byington. Demographic, clinical, disease-free survival (DFS) and overall survival (OS) data were evaluated. Multivariate analysis was performed to assess independent prognostic factors., Results: One hundred seventy-six and 353 patients treated in the neoadjuvant and adjuvant setting were included, respectively. The 3- and 5-year OS rates were 79% and 56% for the neoadjuvant group and 97% and 92% for the adjuvant group, respectively. Node positivity at diagnosis predicted poor OS for both groups. In the neoadjuvant group, stage III disease at diagnosis, delayed surgery, and lack of pathological complete response (pCR) predicted poor prognosis. The 3- and 5-year DFS rates were 67% and 46% in the neoadjuvant group and 91% and 86% in the adjuvant group, respectively. Histological grade 2, stage III disease at diagnosis, and lack of pCR predicted poor DFS for the neoadjuvant group. For the adjuvant group, node positivity at diagnosis predicted poor DFS., Conclusion: Our results reveal multiple clinical parameters affecting survival outcomes according to the treatment setting. Patients treated with neoadjuvant therapy have a poor prognosis since they present with more advanced disease, indicating the importance of early diagnosis and optimized treatment., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2023
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21. Increased Expression of miR-223-3p and miR-375-3p and Anti-Inflammatory Activity in HDL of Newly Diagnosed Women in Advanced Stages of Breast Cancer.
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Santana MFM, Sawada MIBAC, Santos AS, Reis M, Xavier J, Côrrea-Giannella ML, Hirata AHL, Gebrim LH, Soriano FG, Camacho CP, and Passarelli M
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- Humans, Female, Interleukin-6, Anti-Inflammatory Agents pharmacology, Inflammation genetics, Lipoproteins, HDL, Tumor Necrosis Factor-alpha, Breast Neoplasms genetics, MicroRNAs genetics
- Abstract
The expression of inflammation-related miRs bound to high-density lipoproteins (HDLs), the anti-inflammatory activity of HDLs isolated from individuals with breast cancer, and controls were determined. Forty newly diagnosed women with breast cancer naïve of treatment and 10 control participants were included. Cholesterol-loaded bone-marrow-derived macrophages were incubated with HDL from both groups and challenged with lipopolysaccharide (LPS). Interleukin 6 (IL6) and tumor necrosis factor (TNF) in the medium were quantified. The miRs in HDLs were determined by RT-qPCR. Age, body mass index, menopausal status, plasma lipids, and HDL composition were similar between groups. The ability of HDL to inhibit IL6 and TNF production was higher in breast cancer compared to controls, especially in advanced stages of the disease. The miR-223-3p and 375-3p were higher in the HDLs of breast cancer independent of the histological type of the tumor and had a high discriminatory power between breast cancer and controls. The miR-375-3p was greater in the advanced stages of the disease and was inversely correlated with the secretion of inflammatory cytokines. Inflammation-related miRs and the anti-inflammatory role of HDLs may have a significant impact on breast cancer pathophysiology.
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- 2023
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22. Current Challenges and Perspectives in Breast Cancer in Elderly Women: The Senologic International Society (SIS) Survey.
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Scheer L, Lodi M, Özmen T, Alghamdi K, Anyanwu S, Birendra J, Boubnider M, Costa M, Dian D, Elder E, Gebrim LH, Guo X, Heitz D, Imoto S, Ioannidou-Mouzaka L, Kaufman C, Liu H, Mbodj M, Meka E, Mundinger A, Novelli J, Ojuka D, Orda R, Ostapenko V, Pieńkowski T, Podolski P, Vogel T, Yin J, Özmen V, Schneebaum S, and Mathelin C
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Objective: Mammographic screening and management of breast cancer (BC) in elderly women are controversial and continue to be an important health problem. To investigate, through members of the Senologic International Society (SIS), the current global practices in BC in elderly women, highlighting topics of debate and suggesting perspectives., Materials and Methods: The questionnaire was sent to the SIS network and included 55 questions on definitions of an elderly woman, BC epidemiology, screening, clinical and pathological characteristics, therapeutic management in elderly women, onco-geriatric assessment and perspectives., Results: Twenty-eight respondents from 21 countries and six continents, representing a population of 2.86 billion, completed and submitted the survey. Most respondents considered women 70 years and older to be elderly. In most countries, BC was often diagnosed at an advanced stage compared to younger women, and age-related mortality was high. For this reason, participants recommended that personalized screening be continued in elderly women with a long life expectancy.In addition, this survey highlighted that geriatric frailty assessment tools and comprehensive geriatric evaluations needed to be used more and should be developed to avoid undertreatment. Similarly, multidisciplinary meetings dedicated to elderly women with BC should be encouraged to avoid under- and over-treatment and to increase their participation in clinical trials., Conclusion: Due to increased life expectancy, BC in elderly women will become a more important field in public health. Therefore, screening, personalized treatment, and comprehensive geriatric assessment should be the cornerstones of future practice to avoid the current excess of age-related mortality. This survey described, through members of the SIS, a global picture of current international practices in BC in elderly women., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (©Copyright 2023 by the the Turkish Federation of Breast Diseases Societies / European Journal of Breast Health published by Galenos Publishing House.)
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- 2023
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23. Increased plasma lipids in triple-negative breast cancer and impairment in HDL functionality in advanced stages of tumors.
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Sawada MIBAC, de Fátima Mello Santana M, Reis M, de Assis SIS, Pereira LA, Santos DR, Nunes VS, Correa-Giannella MLC, Gebrim LH, and Passarelli M
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- Humans, Female, Apolipoprotein A-I, Gas Chromatography-Mass Spectrometry, Lipoproteins, Cholesterol, Triglycerides, Cholesterol, HDL, Triple Negative Breast Neoplasms, Oxysterols
- Abstract
The association between plasma lipids and breast cancer (BC) has been extensively explored although results are still conflicting especially regarding the relationship with high-density lipoprotein cholesterol (HDLc) levels. HDL mediates cholesterol and oxysterol removal from cells limiting sterols necessary for tumor growth, inflammation, and metastasis and this may not be reflected by measuring HDLc. We addressed recently diagnosed, treatment-naïve BC women (n = 163), classified according to molecular types of tumors and clinical stages of the disease, in comparison to control women (CTR; n = 150) regarding plasma lipids and lipoproteins, HDL functionality and composition in lipids, oxysterols, and apo A-I. HDL was isolated by plasma discontinuous density gradient ultracentrifugation. Lipids (total cholesterol, TC; triglycerides, TG; and phospholipids, PL) were determined by enzymatic assays, apo A-I by immunoturbidimetry, and oxysterols (27, 25, and 24-hydroxycholesterol), by gas chromatography coupled with mass spectrometry. HDL-mediated cell cholesterol removal was determined in macrophages previously overloaded with cholesterol and
14 C-cholesterol. Lipid profile was similar between CTR and BC groups after adjustment per age. In the BC group, lower concentrations of TC (84%), TG (93%), PL (89%), and 27-hydroxicholesterol (61%) were observed in HDL, although the lipoprotein ability in removing cell cholesterol was similar to HDL from CRT. Triple-negative (TN) BC cases presented higher levels of TC, TG, apoB, and non-HDLc when compared to other molecular types. Impaired HDL functionality was observed in more advanced BC cases (stages III and IV), as cholesterol efflux was around 28% lower as compared to stages I and II. The altered lipid profile in TN cases may contribute to channeling lipids to tumor development in a hystotype with a more aggressive clinical history. Moreover, findings reinforce the dissociation between plasma levels of HDLc and HDL functionality in determining BC outcomes., (© 2023. The Author(s).)- Published
- 2023
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24. The increased antioxidant action of HDL is independent of HDL cholesterol plasma levels in triple-negative breast cancer.
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Campos AL, Sawada MIBAC, Santana MFM, Iborra RT, de Assis SIS, Reis M, de Carvalho JX, Gebrim LH, and Passarelli M
- Abstract
Introduction: The association between high-density lipoprotein cholesterol (HDLc) with the incidence and progression of breast cancer (BC) is controversial. HDL removes excess cholesterol from cells and acts as an antioxidant and anti-inflammatory. BC is a heterogeneous disease, and its molecular classification is important in the prediction of clinical and therapeutic evolution. Triple-negative breast cancer (TNBC) presents higher malignancy, lower therapeutic response, and survival rate. In the present investigation, the composition and antioxidant activity of isolated HDL was assessed in women with TNBC compared to controls., Methods: Twenty-seven women with a recent diagnosis of TNBC, without prior treatment, and 27 healthy women (control group) paired by age and body mass index (BMI) were included in the study. HDL and low-density lipoprotein (LDL) were isolated from plasma by discontinuous density gradient ultracentrifugation. Plasma lipid profile and HDL composition (total cholesterol, TC; triglycerides, TG; HDLc; phospholipids, PL) were determined by enzymatic colorimetric methods. ApoB and apo A-I were quantified by immunoturbidimetry. The antioxidant activity of HDL was determined by measuring the lag time phase for LDL oxidation and the maximal rate of conjugated dienes formation in LDL incubated with copper sulfate solution. The absorbance (234 nm) was monitored at 37°C, for 4 h, at 3 min intervals., Results: The control group was similar to the TNBC concerning menopausal status, concentrations, and ratios of plasma lipids. The composition of the HDL particle in TC, TG, PL, and apo A-I was also similar between the groups. The ability of HDL to retard LDL oxidation was 22% greater in the TNBC group as compared to the control and positively correlated with apoA-I in HDL. Moreover, the antioxidant activity of HDL was greater in the advanced stages of TNBC (stages III and IV) compared to the control group. The maximum rate of formation of conjugated dienes was similar between groups and the clinical stages of the disease., Discussion: The results highlight the role of HDL as an antioxidant defense in TNBC independently of HDLc plasma levels. The improved antioxidant activity of HDL, reflected by retardation in LDL oxidation, could contribute to limiting oxidative and inflammatory stress in advanced stages of TNBC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Campos, Sawada, Santana, Iborra, de Assis, Reis, de Carvalho, Gebrim and Passarelli.)
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- 2023
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25. Diagnosing molecular subtypes of breast cancer by means of Raman spectroscopy.
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Melitto AS, Arias VEA, Shida JY, Gebrim LH, and Silveira L Jr
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- Discriminant Analysis, Female, Humans, Least-Squares Analysis, Lipids, Principal Component Analysis, Breast Neoplasms diagnosis, Breast Neoplasms pathology, Spectrum Analysis, Raman methods
- Abstract
Objectives: Raman spectroscopy has been used to discriminate human breast cancer and its different tumor molecular subtypes (luminal A, luminal B, HER2, and triple-negative) from normal tissue in surgical specimens., Materials and Methods: Breast cancer and normal tissue samples from 31 patients were obtained by surgical resection and submitted for histopathology. Before anatomopathological processing, the samples had been submitted to Raman spectroscopy (830 nm, 25 mW excitation laser parameters). In total, 424 Raman spectra were obtained. Principal component analysis (PCA) was used in an exploratory analysis to unveil the compositional differences between the tumors and normal tissues. Discriminant models were developed to distinguish the different cancer subtypes by means of partial least squares (PLS) regression., Results: PCA vectors showed spectral features referred to the biochemical constitution of breast tissues, such as lipids, proteins, amino acids, and carotenoids, where lipids were decreased and proteins were increased in breast tumors. Despite the small spectral differences between the different subtypes of tumor and normal tissues, the discriminant model based on PLS was able to discriminate the spectra of the breast tumors from normal tissues with an accuracy of 97.3%, between luminal and nonluminal subtypes with an accuracy of 89.9%, between nontriple-negative and triple-negative with an accuracy of 94.7%, and each molecular subtype with an accuracy of 73.0%., Conclusion: PCA could reveal the compositional difference between tumors and normal tissues, and PLS could discriminate the Raman spectra of breast tissues regarding the molecular subtypes of cancer, being a useful tool for cancer diagnosis., (© 2022 Wiley Periodicals LLC.)
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- 2022
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26. Substantial Reduction in Adjuvant Chemotherapy With the Use of the 21-Gene Test to Manage Early Breast Cancer in a Public Hospital in Brazil.
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Mattar A, Fonseca GR, Romão MBA, Shida JY, de Oliveira VM, Bastos MCS, Bagnoli F, Rinaldi JF, Stiepcich MMÁ, da Silva MALG, Jakubowski DM, Chao C, Oliveira SC, and Gebrim LH
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- Brazil, Chemotherapy, Adjuvant, Female, Hospitals, Public, Humans, Middle Aged, Neoplasm Recurrence, Local drug therapy, Receptors, Estrogen therapeutic use, Breast Neoplasms drug therapy, Breast Neoplasms genetics
- Abstract
Purpose: We evaluated the impact of 21-gene test results on treatment decisions for patients with early-stage breast cancer treated under the public health care system in Brazil, Sistema Único de Saúde., Methods: Eligible patients treated at Hospital Pérola Byington and Santa Casa de Misericórdia de São Paulo in Brazil were required to have the following characteristics: postsurgery with hormone receptor-positive, human epidermal growth factor 2-negative, node-negative and node-positive, and T1/T2 breast cancer and patients with these characteristics were candidates for adjuvant systemic therapy. Treatment recommendations, chemotherapy plus hormonal therapy (CT + HT) or HT alone, were captured before and after 21-gene test results., Results: From August 2018 to April 2019, 179 women were enrolled. The mean age was 58 years (29-86 years), 135 (76%) were postmenopausal, and 58 (32%) had node-positive breast cancer. Most patients (61%) had a tumor > 2 cm, including 7% with tumors > 4 cm. Using Recurrence Score (RS) result cut points on the basis of the TAILORx trial, 40 (22%) had RS 0-10, 91 (51%) had RS 11-25, and 48 (27%) had RS 26-100. Before 21-gene testing, 162 of 179 (91%) patients were recommended for CT. After testing, 117 of 179 patients (65%) had changes in CT recommendation: 112 (63%) who were initially recommended CT received HT alone and five (3%) who were initially recommended HT alone received CT + HT. After 21-gene testing, 99% of physicians reported strong confidence in their treatment recommendations., Conclusion: The change in clinical practice at these public hospitals was greater than expected: 66% of initial treatment recommendations were changed to omit CT with 21-gene test results. Clinicopathologic features did not correlate well with 21-gene test results and did not adequately identify those most likely to benefit from CT., Competing Interests: André MattarEmployment: Novo NordiskStock and Other Ownership Interests: Novo NordiskHonoraria: DASAConsulting or Advisory Role: Lilly, AstraZeneca, Roche, Novartis, Fleury Group, Exact SciencesSpeakers' Bureau: Exact Sciences, NovartisOther Relationship: Genomic Health, Roche Debbie M. JakubowskiEmployment: Exact SciencesStock and Other Ownership Interests: Exact Sciences Calvin ChaoEmployment: Exact SciencesLeadership: Exact SciencesStock and Other Ownership Interests: Exact Sciences Sergio C. OliveiraEmployment: Exact SciencesTravel, Accommodations, Expenses: Exact SciencesNo other potential conflicts of interest were reported.
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- 2021
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27. Assessment of IGF-1 expression in the peripheral blood of women with recurrent breast cancer.
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Costa-Silva DR, Barros-Oliveira MDC, Alves-Ribeiro FA, Campos-Verdes LC, Nery Junior EJ, Vieira-Valença SF, Vasconcelos-Valença RJ, Soares VM, Pinho-Sobral AL, Sousa EB, Lopes-Costa PV, Dos Santos AR, Viana JL, Cardoso AC, Luz-Borges VM, Pereira RO, Tavares CB, Silva VC, Rodrigues-Junior DM, Gebrim LH, and da Silva BB
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- Adult, Aged, Aged, 80 and over, Brazil epidemiology, Breast Neoplasms pathology, Breast Neoplasms therapy, Case-Control Studies, Cell Differentiation, Cell Proliferation, Cross-Sectional Studies, Female, Gene Expression genetics, Humans, Lymph Nodes pathology, Lymphatic Metastasis, Middle Aged, Neoplasm Grading methods, RNA, Messenger genetics, Breast Neoplasms blood, Breast Neoplasms genetics, Insulin-Like Growth Factor I genetics, Neoplasm Recurrence, Local genetics
- Abstract
Breast cancer is the most common malignancy affecting women worldwide. The insulin-like growth factor 1 (IGF-1) gene encodes a protein responsible for a wide variety of physiological processes, including differentiation and cell proliferation. Despite several studies on tumor tissues, no study has evaluated IGF-1 expression in the peripheral blood of women with recurrent breast cancer.In this cross-sectional study, IGF-1 expression in the peripheral blood of 146 women with breast cancer treated approximately 5 years ago was quantified by quantitative reverse transcription polymerase chain. The women were divided into 2 groups: non-recurrence (n = 85) and recurrence (n = 61). Statistical analysis of the data was performed using ANOVA, Mann-Whitney, and Chi-squared tests (P < .05).The results showed no significant difference in IGF-1 expression between the non-recurrence and recurrence groups (P = .988). In the subgroups of patients with lymph node involvement, no statistically significant difference was observed in IGF-1 expression between women with recurrence and those non-recurrence (P = .113). In patients without lymph node metastases, IGF-1 messenger ribonucleic acid (mRNA) expression levels were significantly higher in the non-recurrence group than in the recurrence group (P = .019). Furthermore, using the median IGF-1 mRNA expression as the cutoff point, it was obtained a statistically significant difference in tumor histological grade among women with recurrent breast cancer (P = .042).These data showed significantly higher IGF-1 expression in women without lymph node metastases in the non-recurrence group compared with the recurrence group. In addition, a significant difference was observed in median IGF-1 mRNA expression in relation to tumor histological grade in women with recurrent breast cancer.
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- 2020
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28. The impact of letrozole administration on oocyte morphology in breast cancer patients undergoing fertility preservation.
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Bercaire LMN, Cavagna M, Donadio NF, Rocha AR, Portela R, Alves VR, Santos TBB, Cavagna F, Dzik A, Gebrim LH, and Nahas EAP
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- Adult, Cell Shape drug effects, Cryopreservation methods, Female, Fertility Preservation, Humans, Infertility, Female pathology, Oocyte Retrieval, Oocytes pathology, Ovulation Induction methods, Retrospective Studies, Antineoplastic Agents administration & dosage, Breast Neoplasms pathology, Infertility, Female therapy, Letrozole administration & dosage, Oocytes drug effects
- Abstract
Abstract: Patients submitted to oncological fertility preservation with letrozole and gonadotropins seem to present a higher rate of immature oocytes and lower fertilization rates in comparison to infertile patients submitted to IVF cycles with gonadotropins. The aim of this study was to evaluate the influence of letrozole on oocyte morphology in patients with breast cancer submitted to fertility preservation., Methods: Retrospective analysis performed at a public tertiary hospital in São Paulo, Brazil. The oocytes were retrieved from patients with breast cancer undergoing fertility preservation (n=69), and from infertile women undergoing in vitro fertilization (n=92). We evaluated 750 oocytes obtained from breast cancer patients submitted to ovarian stimulation with letrozole and gonadotropins, and 699 oocytes from patients without breast cancer submitted to ovarian stimulation for in vitro fertilization with gonadotropins only due to male factor infertility. The mature oocytes retrieved were analyzed for the presence of refractile bodies, ooplasm color and regularity, central granulation degree, cortical granules, zona pellucida staining and regularity, perivitelline space, presence of vacuoles or abnormal smooth-surfaced endoplasmic reticle and oocyte retraction., Results: There was a higher incidence of alterations in oocyte morphology in the letrozole group when compared to the control group: increased perivitelline space (p=0.007), irregular zona pellucida (p<0.001), refractile bodies (p<0.001), dark ooplasm (p<0.001), granular ooplasm (p<0.001), irregular ooplasm (p<0.001) and dense central granulation (p<0.001)., Conclusion: Letrozole is a risk factor for worse oocyte morphology. However, the clinical impact of ovarian stimulation protocol with combined use of gonadotropins and letrozole for fertility preservation remains unclear in this setting. These data underline the importance of establishing the predictive potential of morphological dimorphisms of human oocytes in IVF outcomes.
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- 2020
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29. CYP19A1 gene expression in the peripheral blood of Brazilian women with breast cancer relapse.
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Barros-Oliveira MDC, Costa-Silva DR, Campos-Verdes LC, Pereira RO, Silva RA, Moura-Borges PT, Sousa EB, Pinho-Sobral AL, Lopes-Costa PV, Dos Santos AR, Soares-Lopes IMR, Viana JL, Melo MA, Manes Neto F, Coelho EG, Pires E Cruz MDS, Costa-Silva V, Gebrim LH, and Da Silva BB
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- Adult, Aged, Aged, 80 and over, Aromatase blood, Breast Neoplasms blood, Female, Genes, erbB-2, Humans, Middle Aged, Neoplasm Recurrence, Local blood, Reverse Transcriptase Polymerase Chain Reaction, Aromatase genetics, Breast Neoplasms genetics, Gene Expression, Neoplasm Recurrence, Local genetics, RNA, Messenger blood
- Abstract
Background: The CYP19A1 gene, which encodes the enzyme responsible for androgen aromatization into estrogens, may play an important role in breast cancer aggressiveness. However, no study has evaluated CYP19A1 gene expression in the peripheral blood of women with relapsed breast cancer., Methods: In this cross-sectional study, CYP19A1 gene expression was quantified by RT-PCR in the peripheral blood of 146 women with breast cancer who were first divided into two groups according to the expression of CYP19A1 (low and high); each group had 73 patients. Subsequently, women were divided into two groups: those without recurrence (control, n = 85) and those with recurrence (study, n = 61). Statistical analysis of the data was performed using ANOVA, the Mann-Whitney, Chi-square or Fisher's exact test (p < 0.05)., Results: There were no significant differences between the relative expression of CYP19A1 mRNA in the low expression group and the high expression group according to the variables studied. There were no significant differences in CYP19A1 gene expression in the study and control groups (p = 0.8461). In the relapse group, CYP19A1 gene expression was significantly higher in the hybrid luminal subtype than in the triple-negative subtype (p = 0.0321), whereas it was significantly lower in HER2-negative cases than in HER2-positive cases (p < 0.0376). Women with locoregional recurrence showed higher expression than women with distant recurrence (p < 0.0001)., Conclusions: The present study found no significant differences between women with high and low expression of the CYP19A1 gene mRNA or between those in the study group and the control group. However, in women with recurrence, there was increased expression of CYP19A1 mRNA in those who had the luminal hybrid subtype and locoregional relapse and decreased expression in those negative for HER2.
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- 2020
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30. Breast cancer treatment: A phased approach to implementation.
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Mutebi M, Anderson BO, Duggan C, Adebamowo C, Agarwal G, Ali Z, Bird P, Bourque JM, DeBoer R, Gebrim LH, Masetti R, Masood S, Menon M, Nakigudde G, Ng'ang'a A, Niyonzima N, Rositch AF, Unger-Saldaña K, Villarreal-Garza C, Dvaladze A, El Saghir NS, Gralow JR, and Eniu A
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- Brazil, Checklist, Combined Modality Therapy, Delayed Diagnosis, Developed Countries, Female, Health Plan Implementation, Humans, Interdisciplinary Communication, Kenya, Romania, Time-to-Treatment, Breast Neoplasms diagnosis, Breast Neoplasms therapy
- Abstract
Optimal treatment outcomes for breast cancer are dependent on a timely diagnosis followed by an organized, multidisciplinary approach to care. However, in many low- and middle-income countries, effective care management pathways can be difficult to follow because of financial constraints, a lack of resources, an insufficiently trained workforce, and/or poor infrastructure. On the basis of prior work by the Breast Health Global Initiative, this article proposes a phased implementation strategy for developing sustainable approaches to enhancing patient care in limited-resource settings by creating roadmaps that are individualized and adapted to the baseline environment. This strategy proposes that, after a situational analysis, implementation phases begin with bolstering palliative care capacity, especially in settings where a late-stage diagnosis is common. This is followed by strengthening the patient pathway, with consideration given to a dynamic balance between centralization of services into centers of excellence to achieve better quality and decentralization of services to increase patient access. The use of resource checklists ensures that comprehensive therapy or palliative care can be delivered safely and effectively. Episodic or continuous monitoring with established process and quality metrics facilitates ongoing assessment, which should drive continual process improvements. A series of case studies provides a snapshot of country experiences with enhancing patient care, including the implementation of national cancer control plans in Kenya, palliative care in Romania, the introduction of a 1-stop clinic for diagnosis in Brazil, the surgical management of breast cancer in India, and the establishment of a women's cancer center in Ghana., (© 2020 American Cancer Society.)
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- 2020
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31. Expression of Nrf2 and NF-κB transcription factors in breast cancer and breast fibroadenoma: Insights for a new therapeutic approach.
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Simplicio-Revoredo CM, de Oliveira Pereira R, de Almeida Melo M, Lopes-Costa PV, de Tarso Moura-Borges P, Sousa EB, Neto FM, Campelo V, Soares-Lopes IMR, da Conceição Barros-Oliveira M, Tavares CB, Dos Santos AR, de Araújo CGB, Coelho EG, Campos-Verdes LC, do Nascimento-Holanda AO, Viana JL, Bezerra-Chaves MLM, de Vasconcelos-Valença RJ, Dos Santos LG, Soares-Lopes LR, Pinho-Sobral AL, Gebrim LH, and da Silva BB
- Abstract
Background: Cancer and fibroadenoma are the most common breast tumors in women of reproductive age. Nuclear factor erythroid 2-related factor 2 (Nrf2) and the nuclear factor kappaB (NF-κB) transcription factor play an important role in the inflammatory process and in cell proliferation. However, few studies have analyzed these markers in breast cancer and fibroadenoma in women of reproductive age. Results: Light microscopy showed a higher concentration of anti-Nrf2 and anti-NF-κB-stained nuclei in breast cancer than in fibroadenoma. The mean percentage of stained nuclei for Nrf2 was 7.12 ± 5.2 and 43.21 ± 19.83 in the control and study groups, respectively (p < 0.0001). The mean percentage of anti-NF-κB was 10.75 ± 7.09 and 56.14 ± 21.19 (mean ± standard deviation) in the control and study groups, respectively (p < 0.0001). Histological grade 3 tumors showed a significantly higher expression of Nrf2 and NF-κB than grade 1 tumors (p < 0.05). Material and methods: This study was approved by the Institutional Review Board of Federal University of Piaui and all patients assigned an inform consent term prior to the study initiation. Nrf2 and NF-κB expression was evaluated by immunohistochemistry in 66 patients, divided into two groups, control (fibroadenoma, n = 36) and study (cancer, n = 30). The data were analyzed using ANOVA test and the statistical significance was established at p < 0.05. Conclusion: Nrf2 and NF-κB expression was significantly higher in breast cancer than in fibroadenoma, in addition to having a greater association with more aggressive tumors., Competing Interests: CONFLICTS OF INTEREST The authors declare that they have no competing interests., (Copyright: © 2020 Simplicio-Revoredo et al.)
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- 2020
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32. Prevalence and risk factors of medication-related osteonecrosis of the jaw in osteoporotic and breast cancer patients: a cross-sectional study.
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Soares AL, Simon S, Gebrim LH, Nazário ACP, and Lazaretti-Castro M
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- Adult, Aged, Aged, 80 and over, Biomarkers blood, Bisphosphonate-Associated Osteonecrosis of the Jaw blood, Bone Density Conservation Agents adverse effects, Bone Density Conservation Agents therapeutic use, Cross-Sectional Studies, Diphosphonates adverse effects, Diphosphonates therapeutic use, Female, Humans, Middle Aged, Osteocalcin blood, Osteoporosis blood, Osteoporosis drug therapy, Parathyroid Hormone blood, Prevalence, Risk Factors, Vitamin D analogs & derivatives, Vitamin D blood, Bisphosphonate-Associated Osteonecrosis of the Jaw epidemiology, Breast Neoplasms blood, Breast Neoplasms drug therapy
- Abstract
Purpose: Medication-related osteonecrosis of the jaw (MRONJ) has been reported as a side effect of bisphosphonate (BP). The aim of this study was to identify the prevalence of MRONJ in women taking BP for osteoporosis and for metastatic breast cancer and correlate it with risk factors and biochemical markers of bone metabolism., Methods: Patients taking oral or intravenous BP with osteoporosis (G1; n = 153; median 72.8 years) and with metastatic breast cancer (G2; n = 134; median 58.2 years) had their hospital charts reviewed, were submitted to dental inspection, and answered a health questionnaire. Fasting blood samples were randomly collected from both groups to measure osteocalcin, carboxy-terminal cross-linking telopeptide of type I collagen, intact parathyroid hormone and procollagen type 1 amino-terminal propeptide (P1NP), 25 hydroxyvitamin D (25OHD), creatinine, and total calcium., Results: G1 was older (p = 0.001) and had more cases of diabetes (p = 0.043). P1NP was higher (p = 0.022) and 25OHD lower (p = 0.004) in G2 compared with G1. MRONJ was not found in the G1, whereas 4 cases (3%) were detected in G2. Positive risk factors for MRONJ were number of BP doses and number of visits to the dentist and dental extractions. The biochemical parameters, however, could not identify those who developed MRONJ., Conclusions: The prevalence of MRONJ was 3% in women with metastatic breast cancer receiving BP. No cases were identified in women receiving oral BP chronically for osteoporosis. P1NP was higher in women with metastatic breast cancer, even during treatment with antiresorptives, but could not differentiate those with MRONJ.
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- 2020
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33. Expression of matrix metalloproteinase 2 and 9 in breast cancer and breast fibroadenoma: a randomized, double-blind study.
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Martins LM, de Melo Escorcio Dourado CS, Campos-Verdes LM, Sampaio FA, Revoredo CMS, Costa-Silva DR, da Conceição Barros-Oliveira M, de Jesus Nery Junior E, do Rego-Medeiros LM, Gebrim LH, Alves-Ribeiro FA, Rodrigues GP, Chagas DC, do Nascimento Marreiro D, and da Silva BB
- Abstract
Background: Matrix metalloproteinases (MMPs) 2 and 9 may play an important role in cell proliferation and dissemination of cancer. However, few studies have compared the expression of these proteins between breast cancer and fibroadenoma., Material and Methods: A randomized, double-blind study was carried out in 66 premenopausal women, aged 20-49 years, who had been diagnosed with fibroadenoma or breast cancer. The patients were divided into two groups: Group A, control (fibroadenoma, n=36) and Group B, study (cancer, n=30). Immunohistochemical analysis was performed using tissue samples of fibroadenoma and breast cancer to assess MMP-2 and MMP-9 antigen expression. Cells were considered positive if exhibiting brown cytoplasmic staining. Fisher's exact test was used to compare the percentage of cases with cells expressing MMP-2 and MMP-9 in control and study groups (p < 0.05)., Results: Light microscopy showed a higher concentration of cells with positive cytoplasmic staining for MMP-2 and MMP-9 expression in breast cancer than in fibroadenoma. The percentage of cases with cells expressing MMP-2 in the control and study groups was 41.67% and 86.11%, respectively (p < 0.0009), whereas the percentage of cases with cells expressing MMP-9 in groups A and B was 66.67% and 93.33%, respectively (p<0.0138). MMP-2 and MMP-9 positive expression was significantly higher in moderately differentiated tumors compared to well and poorly differentiated tumors, p <0.005 and p<0.001, respectively., Conclusions: The current study shows that MMP-2 and MMP-9 protein expression was significantly higher in the breast cancer than in the fibroadenoma and also in moderately differentiated breast cancer., Competing Interests: CONFLICTS OF INTEREST The authors have no conflict of interest., (Copyright: © 2019 Martins et al.)
- Published
- 2019
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34. Impaired brain dopamine transporter in chemobrain patients submitted to brain SPECT imaging using the technetium-99m labeled tracer TRODAT-1.
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Vitor T, Kozasa EH, Bressan RA, Lacerda SS, Campos Neto GC, Batista IR, Gebrim LH, Cohen L, Amaro E, and Felicio AC
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- Adult, Antineoplastic Agents therapeutic use, Brain drug effects, Brain physiology, Breast Neoplasms drug therapy, Case-Control Studies, Cognition drug effects, Female, Humans, Radioactive Tracers, Antineoplastic Agents adverse effects, Brain diagnostic imaging, Brain metabolism, Dopamine Plasma Membrane Transport Proteins metabolism, Organotechnetium Compounds, Tomography, Emission-Computed, Single-Photon, Tropanes
- Abstract
Purpose: "Chemobrain" is a medical secondary effect of cancer chemotherapy treatment characterized by a general decline in cognition affecting visual and verbal memory, attention, complex problem-solving skills, and motor function. Dopamine (DA) central nervous system neurotransmitters serve an important role in cognition, and changes in DA could potentially explain impaired cognition associated with chemotherapy. Therefore, our objective was to assess in vivo dopaminergic dysfunction in the central nervous system (CNS) of a group of female breast cancer survivors with cognitive impairment following chemotherapy., Methods: Twenty-eight women reporting chemobrain were recruited for this study and compared to 22 healthy reference women. Striatal dopamine transporter (DAT) binding ratio was determined by
99m Tc-TRODAT-1 (a highly selective radiotracer for DAT in the dorsal striatum) single-photon emission computed tomography and a quantitative evaluation was obtained by DatQUANT™ software (GE Healthcare). The DAT binding ratio (BRDAT ) in the patient and control groups was compared using the Student's t test, a multivariate analysis of variance (MANOVA) was used to compare age, years of schooling and BRDAT . The relationship between continuous variables, such as cognitive impairment and BRDAT was assessed using Pearson correlation test., Results: There was a difference in BRDAT between the chemobrain patients and control group. Patients had statistically significant (p < 0.05) lower concentrations of the radiopharmaceutical in the striatum., Conclusions: We identified a significant dopaminergic decrease in all regions of the dorsal striatum within the patients reporting cognitive dysfunction after chemotherapy. Therefore, our results indicate a possible role of dopamine transporter in the physiopathology of chemobrain, even out of the acute phase of symptoms.- Published
- 2019
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35. Specific protocols of controlled ovarian stimulation for oocyte cryopreservation in breast cancer patients.
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Cavagna F, Pontes A, Cavagna M, Dzik A, Donadio NF, Portela R, Nagai MT, and Gebrim LH
- Subjects
- Adult, Female, Gonadotropin-Releasing Hormone administration & dosage, Gonadotropins administration & dosage, Humans, Oocytes cytology, Oocytes metabolism, Breast Neoplasms, Cryopreservation methods, Fertility Preservation methods, Ovulation Induction methods
- Abstract
Background: Fertility preservation is an important concern in breast cancer patients. In the present investigation, we set out to create a specific protocol of controlled ovarian stimulation (cos) for oocyte cryopreservation in breast cancer patients., Methods: From November 2014 to December 2016, 109 patients were studied. The patients were assigned to a specific random-start ovarian stimulation protocol for oocyte cryopreservation. The endpoints were the numbers of oocytes retrieved and of mature oocytes cryopreserved, the total number of days of ovarian stimulation, the total dose of gonadotropin administered, and the estradiol level on the day of the trigger., Results: Mean age in this cohort was 31.27 ± 4.23 years. The average duration of cos was 10.0 ± 1.39 days. The mean number of oocytes collected was 11.62 ± 7.96 and the mean number of vitrified oocytes was 9.60 ± 6.87. The mean estradiol concentration on triggering day was 706.30 ± 450.48 pg/mL, and the mean dose of gonadotropins administered was 2610.00 ± 716.51 IU. When comparing outcomes by phase of the cycle in which cos was commenced, we observed no significant differences in the numbers of oocytes collected and vitrified, the length of ovarian stimulation, and the estradiol level on trigger day. The total dose of follicle-stimulating hormone and human menopausal gonadotropin administered was statistically greater in the group starting cos in the luteal phase than in the group starting in the late follicular phase., Conclusions: Our results suggest that using a specific protocol with random-start ovarian stimulation for oocyte cryopreservation in breast cancer patients is effective and could be offered to young women undergoing oncologic treatment., Competing Interests: CONFLICT OF INTEREST DISCLOSURES We have read and understood Current Oncology’s policy on disclosing conflicts of interest, and we declare that we have none.
- Published
- 2018
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36. A rare case of primary breast angiosarcoma in a male: a case report.
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da Silva BB, Eulálio Filho WMN, Costa PVL, Silva RA, Junior AMC, Chagas DC, de Almeida Melo M, Neto FM, Tavares CB, de Sousa Júnior EC, Coelho EG, Campelo V, Gebrim LH, and da Silva Junior RG
- Subjects
- Adult, Chemotherapy, Adjuvant, Humans, Male, Brain Neoplasms secondary, Breast Neoplasms, Male pathology, Breast Neoplasms, Male therapy, Hemangiosarcoma pathology, Hemangiosarcoma therapy, Paclitaxel therapeutic use
- Abstract
Background: Sarcomas account for less than 1% of primary breast cancers, and breast angiosarcomas are responsible for only 0.05% of all breast malignancies. The male breast has the same potential for malignant transformation as the female breast. However, due to anatomical differences in the breast and the low incidence of angiosarcoma, it is difficult to determine how male breasts can be affected by this type of tumor., Case Presentation: A 36-year-old male patient was admitted to the hospital with a palpable lump in his right breast. Lymphadenopathy was negative. Ultrasonography showed a hypoechoic mass with partially defined contours, measuring 4.0 × 3.0 cm, with muscle infiltration. Histological examination revealed a malignant tumor. Radical mastectomy was then performed with clear surgical margins. The patient began chemotherapy with paclitaxel. Following the second cycle of chemotherapy, he presented with headache and seizures due to a frontal lobe metastasis. Twenty days after the onset of neurological symptoms, the patient died., Conclusions: Primary angiosarcomas of the male breast are extremely rare. This is the sixth case published in the literature. It is in agreement with other studies in the literature concerning clinical presentation and poor prognosis. Treatment consists in surgical removal of the tumor with clear margins and without axillary lymphadenectomy.
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- 2018
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37. Cardiac autonomic modulation impairments in advanced breast cancer patients.
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Arab C, Vanderlei LCM, da Silva Paiva L, Fulghum KL, Fristachi CE, Nazario ACP, Elias S, Gebrim LH, Ferreira Filho C, Gidron Y, and Ferreira C
- Subjects
- Adult, Aged, Arrhythmias, Cardiac physiopathology, Biopsy, Breast Neoplasms pathology, Cross-Sectional Studies, Electrocardiography, Female, Humans, Middle Aged, Neoplasm Staging, Arrhythmias, Cardiac etiology, Breast Neoplasms complications, Heart Rate physiology, Vagus Nerve physiopathology
- Abstract
Aim: To compare cardiac autonomic modulation in early- versus advanced-stage breast cancer patients before any type of cancer treatment and investigate associated factors., Methods and Results: This cross-sectional study included women (30-69 years old) with primary diagnosis of breast cancer and women with benign breast tumors. We evaluated cardiac modulation by heart rate variability and assessed factors of anxiety, depression, physical activity, and other relevant medical variables. Patients were divided into three groups based on TNM staging of cancer severity: early-stage cancer (n = 42), advanced-stage cancer (n = 37), or benign breast tumors to serve as a control (n = 37). We analyzed heart rate variability in time and frequency domains. The advanced-stage cancer group had lower vagal modulation than early-stage and benign groups; also, the advance-stage group had lower overall heart rate variability when compared to benign conditions. Heart rate variability was influenced by age, menopausal status, and BMI., Conclusions: Heart rate variability seems to be a promising, non-invasive tool for early diagnosis of autonomic dysfunction in breast cancer and detection of cardiovascular impairments at cancer diagnosis. Cardiac autonomic modulation is inversely associated with breast cancer staging.
- Published
- 2018
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38. Preimplantation genetic diagnosis for a patient with multiple endocrine neoplasia type 1: case report.
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Lima AD, Alves VR, Rocha AR, Martinhago AC, Martinhago C, Donadio N, Dzik A, Cavagna M, and Gebrim LH
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- Adult, Biopsy, Female, Fertilization in Vitro, Genetic Testing methods, Humans, Male, Pedigree, Pregnancy, Sperm Injections, Intracytoplasmic, Blastocyst pathology, Multiple Endocrine Neoplasia Type 1 genetics, Multiple Endocrine Neoplasia Type 1 pathology, Preimplantation Diagnosis methods
- Abstract
Preimplantation genetic diagnosis was carried out for embryonic analysis in a patient with multiple endocrine neoplasia type 1 (MEN1). This is a rare autosomal-dominant cancer syndrome and the patients with MEN1 are characterized by the occurrence of tumors in multiple endocrine tissues, associated with germline and somatic inactivating mutations in the MEN1 gene. This case report documents a successful preimplantation genetic diagnosis (PGD) involving a couple at-risk for MEN1 syndrome, with a birth of a healthy infant. The couple underwent a cycle of controlled ovarian stimulation and intracytoplasmic sperm injection (ICSI). Embryos were biopsied at the blastocyst stage and cryopreserved; we used PCR-based DNA analysis for PGD testing. Only one of the five embryos analyzed for MEN1 syndrome was unaffected. This embryo was thawed and transferred following endometrial preparation. After positive βHCG test; clinical pregnancy was confirmed by ultrasound, and a healthy infant was born. PGD for single gene disorders has been an emerging therapeutic tool for couples who are at risk of passing a genetic disease on to their offspring.
- Published
- 2018
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39. Genetic polymorphism of calcium-sensing receptor in women with breast cancer.
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Campos-Verdes LM, da Silva-Sampaio JP, Costa-Silva DR, de Oliveira VA, Junior AMC, Silva VC, Alencar AP, Campelo V, Lopes-Costa PV, Gebrim LH, and da Silva BB
- Subjects
- Breast Neoplasms pathology, Case-Control Studies, Cross-Sectional Studies, Female, Follow-Up Studies, Genetic Predisposition to Disease, Humans, Middle Aged, Prognosis, Biomarkers, Tumor genetics, Breast Neoplasms genetics, Polymorphism, Single Nucleotide, Receptors, Calcium-Sensing genetics
- Abstract
Breast cancer is a disease of unknown etiology, whose major risk factors are genetic alterations. Polymorphism of the calcium-sensing receptor (CaSR) has been a focus of some recent studies, due to a probable association with breast cancer risk and tumor aggressiveness. A relationship between polymorphic rs17251221 variant of the CaSR gene, and allele G (considered a gain-of-function mutation) and breast cancer risk has been stressed, despite the paucity of studies found in the literature. The present study involved 137 women (69 women with breast cancer-case; and 68 controls without breast cancer) who had 3 ml of peripheral blood drawn for DNA study. Genomic DNA was extracted from leukocytes by genotyping technique with real-time polymerase chain reaction. The AG genotype (rs17251221) was present in 13 women (18.84%) from the case group and in 8 (11.76%) women from the control group (p = 0.3434), while the GG genotype (rs17251221) did not occur in any group. In contrast, no statistically significant difference was observed between the AG genotype of variant rs17251221 in premenopausal case and control women (p = 0.71). There was also no statistically significant difference between postmenopausal case and control patients (p = 0.6851). In the current study, CaSR gene polymorphism of SNP variant rs17251221 did not show any statistically significant association with breast cancer, in both premenopausal and postmenopausal women.
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- 2018
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40. A comparative study of Ki-67 antigen expression between luminal A and triple-negative subtypes of breast cancer.
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Borges US, Costa-Silva DR, da Silva-Sampaio JP, Escórcio-Dourado CS, Conde AM Jr, Campelo V, Gebrim LH, da Silva BB, and Lopes-Costa PV
- Subjects
- Adult, Biomarkers, Tumor metabolism, Cell Proliferation physiology, Cross-Sectional Studies, Female, Humans, Middle Aged, Receptor, ErbB-2 metabolism, Receptors, Estrogen metabolism, Receptors, Progesterone metabolism, Ki-67 Antigen metabolism, Triple Negative Breast Neoplasms metabolism
- Abstract
Tumor biomarkers such as hormone receptors, HER-2 and Ki-67 are used routinely in clinical practice for classification of molecular subtypes of breast cancer. Cell proliferation evaluated by Ki-67 antigen expression is important to determine tumor aggressiveness. However, there is a paucity of studies comparing Ki-67 expression in an expressive number of cells among molecular subtypes of breast cancer, particularly among less and more aggressive tumors, such as luminal A and triple-negative, which have led us to the present study. The current study included invasive ductal carcinoma samples of 59 patients, which were divided into two groups: luminal A (n = 29) and triple-negative (n = 30). For immunohistochemical reaction, the samples were incubated with monoclonal anti-Ki-67 antibody (clone MIB1) and cells expressing Ki-67 protein were identified by dark brown staining of the nuclei, counting at least 600 cells per slide. The mean percentages of stained nuclei were analyzed by Student's t test (p < 0.05). The mean percentage of nuclei stained with anti-ki-67 was 10.14 and 77.22 in luminal A and triple-negative breast cancers, respectively (p < 0.0001). Our study showed a high cell proliferation of triple-negative breast cancer in comparison with luminal A, justifying its aggressiveness and poor clinical outcome.
- Published
- 2017
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41. Comparative study between ultrasound-guided fine needle aspiration cytology of axillary lymph nodes and sentinel lymph node histopathology in early-stage breast cancer.
- Author
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Cardoso-Coelho LP, Borges RS, Alencar AP, Cardoso-Campos-Verdes LM, da Silva-Sampaio JP, Borges US, Gebrim LH, and da Silva BB
- Abstract
The replacement of sentinel lymph node biopsy (SNB) by ultrasound-guided fine-needle aspiration (US-guided FNA) cytology of axillary lymph nodes is controversial, despite the simplicity and reduced cost of the latter. In the present study, US-guided FNA was performed in 27 patients with early-stage breast cancer for comparison with SNB. Data were analyzed by calculation of sample proportions. Tumor subtypes included invasive ductal carcinoma (85%), invasive lobular carcinoma (7%), and tubular and metaplastic carcinoma (4%). FNA had a sensitivity of 45%, specificity of 100%, positive predictive value of 100% and a negative predictive value of 73%. Axillary lymph node cytology obtained by US guided-FNA in patients with breast cancer had a specificity similar to that of sentinel lymph node histopathology in the presence of axillary node metastases. However, when lymph node cytology is negative, it does not exclude the existence of metastatic implants, due to its low sensitivity in comparison to sentinel lymph node histopathology.
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- 2017
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42. A specific controlled ovarian stimulation (COS) protocol for fertility preservation in women with breast cancer undergoing neoadjuvant chemotherapy.
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Cavagna F, Pontes A, Cavagna M, Dzik A, Donadio NF, Portela R, Nagai MT, and Gebrim LH
- Abstract
Aim of the Study: The authors present a novel and specific controlled ovarian stimulation protocol for fertility preservation in women with estrogen-positive receptor breast cancer undergoing neoadjuvant chemotherapy. The protocol foresees random start ovarian stimulation and the use of letrozole associated to tamoxifen., Material and Methods: Forty breast cancer patients were included in the study. COS was performed either with recombinant FSH or hMG. Concomitantly with COS, letrozole in a dose of 5 mg and tamoxifen in a dose of 20 mg were given orally on a daily basis. The trigger was performed with 0.2 mg of triptorelin, in the presence of follicles ≥ 19 mm. Oocyte retrieval was scheduled 35-36 hours after triptorelin injection. Our main outcome measures were the number of oocytes collected and number of oocytes vitrified, the length of ovarian stimulation, total dose of gonadotropins administered, and levels of estradiol on the day of the trigger., Results: The mean age of patients was 30.43 ±4.25 years. Nineteen women commenced COS in the luteal phase, eleven in the early follicular phase and ten in the late follicular phase. The mean number of collected oocytes was 11.78 ±9.12 and the mean number of vitrified oocytes was 9.72 ±7.36. The mean duration of COS was 10.03 ±1.33 days. The mean estradiol concentrations on the triggering day was 623.10 ±441.27, and the mean dose of gonadotropins administered was 2540 ±713.10., Conclusions: The authors suggest that the protocol is efficient and may be a safe option for oocyte vitrification in these patients., Competing Interests: The authors declare no conflict of interest.
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- 2017
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43. [Not Available].
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Gebrim LH
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- 2016
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44. Lymph node micrometastases in initial stage cervical cancer and tumoral recurrence.
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Colturato LF, Signorini Filho RC, Fernandes RC, Gebrim LH, and Oliani AH
- Subjects
- Adult, Aged, Brazil, Female, Follow-Up Studies, Humans, Lymphatic Metastasis, Middle Aged, Neoplasm Invasiveness, Neoplasm Staging, Prevalence, Retrospective Studies, Risk Factors, Uterine Cervical Neoplasms surgery, Young Adult, Hysterectomy, Neoplasm Micrometastasis pathology, Neoplasm Recurrence, Local epidemiology, Uterine Cervical Neoplasms pathology
- Abstract
Objective: To evaluate the prevalence of micrometastases in lymph node tissue of patients with stage Ib1-IIA cervical cancer, the correlation of micrometastases with tumor recurrence and survival, and the expression of D2-40 in the primary tumor of patients with recurrence and/or micrometastases and its correlation with histopathologic findings., Methods: In a retrospective study, the medical records of all patients with cervical cancer treated at a hospital in São Paulo, Brazil, between 2001 and 2007 were reviewed. Patients with no lymph node metastases and treated with radical hysterectomy without adjuvant treatment were included. Tumor sections were reviewed and lymph nodes were analyzed with AE1/AE3. Patients with and without recurrence were compared. The presence of lymph node micrometastasis or isolated tumor cells was also evaluated., Results: Of the 83 patients evaluated, 15 (18%) had recurrence. Significant differences between patients with and without recurrence were observed with regard to tumor greatest axis, clinical stage, number of micrometastases, and negative lymph nodes (P≤0.04). Lymph node micrometastases and isolated tumor cells were significantly different for a stromal invasion depth greater than 2/3 (P=0.046)., Conclusion: The presence of lymph node micrometastases is an important risk factor for tumor recurrence. These patients should be considered eligible for adjuvant radiochemotherapy treatment., (Copyright © 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.)
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- 2016
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45. Effect of the association of 1-methyl-DL-tryptophan with paclitaxel on the expression of indoleamine 2,3-dioxygenase in cultured cancer cells from patients with breast cancer.
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Salvadori ML, da Cunha Bianchi PK, Gebrim LH, Silva RS, and Kfoury JR Jr
- Subjects
- Antineoplastic Combined Chemotherapy Protocols administration & dosage, Female, Humans, Indoleamine-Pyrrole 2,3,-Dioxygenase metabolism, Tryptophan administration & dosage, Tumor Cells, Cultured, Antineoplastic Agents, Phytogenic administration & dosage, Breast Neoplasms enzymology, Gene Expression Regulation, Neoplastic, Indoleamine-Pyrrole 2,3,-Dioxygenase antagonists & inhibitors, Paclitaxel administration & dosage, Tryptophan analogs & derivatives
- Abstract
Breast cancer is the most common type of cancer among women and the survival of patients affected by it is increasing, mainly due to several new approaches in early diagnosis and more effective treatments. The enzyme indoleamine 2,3-dioxygenase (IDO) is expressed in many cells, including tumor cells. IDO acts by inhibiting the proliferation of T lymphocytes, thus compromising their cytotoxic activity. 1-Methyl-DL-tryptophan (1MT) is a competitive inhibitor of IDO, which blocks its immunosuppressive effect. Paclitaxel is an antineoplastic drug largely used in breast cancer therapy. Thus, this study aimed to determine the in vitro effect of the association of 1MT and paclitaxel chemotherapy, as an approach to reduce tumor growth. It is believed that this would allow the restoration of T lymphocyte proliferation capability and its cytotoxic response. The supplemented cultures showed that the most significant differences in the expression of IDO were observed in the group treated with paclitaxel associated with 1-MT continuous supplementation, reducing enzyme expression from 12.06 to 3.56 %. This association was more effective in reducing IDO expression and could collaborate in developing a new therapeutic strategy for breast cancer treatment.
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- 2015
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46. A rare case of severe myositis as paraneoplastic syndrome on breast cancer.
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Dias LP, Faria AL, Scandiuzzi MM, Inhaia CL, Shida JY, and Gebrim LH
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- Breast Neoplasms pathology, Dermatomyositis etiology, Dermatomyositis therapy, Diagnosis, Differential, Female, Humans, Middle Aged, Paraneoplastic Syndromes etiology, Paraneoplastic Syndromes therapy, Polymyositis etiology, Polymyositis therapy, Prognosis, Breast Neoplasms complications, Dermatomyositis diagnosis, Paraneoplastic Syndromes diagnosis, Polymyositis diagnosis
- Abstract
Background: Dermatomyositis and polymyositis are both types of idiopathic inflammatory myositis characterized by inflammation and weakness of proximal skeletal muscles and skin rash., Case: A 49-year-old Caucasian woman recently diagnosed with breast cancer classified as T1N2M0, stage IIIA, presenting skin rash associated with heliotrope and Gottron's papules. In addition, there was a progression to a severe reduction in proximal muscle strength with severe dysphagia. The initial treatment was conducted, and the patient recovered from all symptoms and followed adjuvant cancer management., Treatment: At first, high dose of corticosteroid was administered as pulse therapy, and a radical mastectomy was indicated due to the severe symptoms of the paraneoplastic syndrome. Then chemotherapy and radiotherapy were applied, and oral corticoid associated with immunosupressive drug was administered for dermatomyositis control., Discussion: The association between myositis and an increased risk of cancer has been demonstrated over the years. This patient has a high probability of dermatomyositis diagnosis. The initial treatment with high dose of glucocorticoids may result in an improvement of muscle lesions. Second-line treatment with azathioprine, methotrexate, or cyclophosphamide may be required for aggressive disease. Removal of the cancer induces improvement of paraneoplastic syndrome., Conclusion: Dermatomyositis can be a clinical manifestation of a paraneoplastic syndrome in patients with breast cancer. It is a rare diagnosis, and there is little evidence to guide treatment until now. It is possible to control the evolution of dermatomyositis with high doses of glucocorticoids in almost all cases; however, in severe cases of paraneoplastic syndrome, cancer treatment should start immediately.
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- 2015
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47. Evaluation of bone metastases from breast cancer by bone scintigraphy and positron emission tomography/computed tomography imaging.
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Pires AO, Borges US, Lopes-Costa PV, Gebrim LH, and da Silva BB
- Subjects
- Bone Neoplasms secondary, Carcinoma secondary, Female, Fluorodeoxyglucose F18, Humans, Middle Aged, Multimodal Imaging, Positron-Emission Tomography, Radionuclide Imaging, Radiopharmaceuticals, Sensitivity and Specificity, Technetium Tc 99m Medronate, Tomography, X-Ray Computed, Bone Neoplasms diagnostic imaging, Breast Neoplasms pathology, Carcinoma diagnostic imaging
- Abstract
Objective: The aim of this study was to compare bone scintigraphy (BS) and positron emission tomography/computed tomography (PET/CT) for the detection of bone metastases from breast cancer., Study Design: Twenty patients with breast cancer and bone pain were submitted to both bone scintigraphy and 18-F-fluorodeoxyglucose PET/CT imaging between July 2012 and June 2013. Scintigraphy was performed following an intravenous injection of technetium-99m-methylene diphosphonate (99mTc-MDP) around 10 days before the PET/CT scan, performed using an intravenous injection of 18-F-fluorodeoxyglucose followed by whole-body computed tomography (CT) to characterize metastases by both methods. Student's t-test for paired samples was used in the comparative data analysis, with significance at p<0.05., Results: CT identified 429 metastatic implants in the 20 patients, with scintigraphy showing 244 of these lesions (57%) and PET/CT showing 307 (72%); however, there was no statistically significant difference between the mean number of lesions detected per patient with the two imaging modalities (p=0.367)., Conclusion: In the present study, no difference was found between PET/CT and bone scintigraphy in the detection of bone metastases from breast cancer., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2014
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48. Estrogen receptor alpha/beta ratio and estrogen receptor beta as predictors of endocrine therapy responsiveness-a randomized neoadjuvant trial comparison between anastrozole and tamoxifen for the treatment of postmenopausal breast cancer.
- Author
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Madeira M, Mattar A, Logullo AF, Soares FA, and Gebrim LH
- Subjects
- Adult, Aged, Aged, 80 and over, Anastrozole, Antineoplastic Agents, Hormonal administration & dosage, Breast Neoplasms pathology, Female, Humans, Immunohistochemistry, Ki-67 Antigen metabolism, Middle Aged, Neoadjuvant Therapy, Neoplasm Staging, Nitriles therapeutic use, Postmenopause, Prognosis, Tamoxifen administration & dosage, Treatment Outcome, Triazoles therapeutic use, Antineoplastic Agents, Hormonal therapeutic use, Breast Neoplasms drug therapy, Breast Neoplasms metabolism, Estrogen Receptor alpha metabolism, Estrogen Receptor beta metabolism, Nitriles administration & dosage, Tamoxifen therapeutic use, Triazoles administration & dosage
- Abstract
Background: The role of estrogen receptor beta (ER-β) in breast cancer (BC) remains unclear. Some studies have suggested that ER-β may oppose the actions of estrogen receptor alpha (ER-α), and clinical evidence has indicated that the loss of ER-β expression is associated with a poor prognosis and resistance to endocrine therapy. The objective of the present study was to determine the role of ER-β and the ER-α/ER-β ratio in predicting the response to endocrine therapy and whether different regimens have any effect on ER-β expression levels., Methods: Ninety postmenopausal patients with primary BC were recruited for a short-term double-blinded randomized prospective controlled study. To determine tumor cell proliferation, we measured the expression of Ki67 in tumor biopsy samples taken before and after 26 days of treatment with anastrozole 1 mg/day (N = 25), tamoxifen 20 mg/day (N = 24) or placebo (N = 29) of 78 participants. The pre- and post-samples were placed in tissue microarray blocks and submitted for immunohistochemical assay. Biomarker statuses (ER-β, ER-α and Ki67) were obtained by comparing each immunohistochemical evaluation of the pre- and post-surgery samples using the semi-quantitative Allred's method. Statistical analyses were performed using an ANOVA and Spearman's correlation coefficient tests, with significance at p ≤ 0.05., Results: The frequency of ER-β expression did not change after treatment (p = 0.33). There were no significant changes in Ki67 levels in ER-β-negative cases (p = 0.45), but in the ER-β-positive cases, the anastrozole (p = 0.01) and tamoxifen groups (p = 0.04) presented a significant reduction in post-treatment Ki67 scores. There was a weak but positive correlation between the ER-α and ER-β expression levels. Only patients with an ER-α/ER-β expression ratio between 1 and 1.5 demonstrated significant differences in Ki67 levels after treatment with anastrozole (p = 0.005) and tamoxifen (p = 0.026)., Conclusions: Our results provide additional data that indicate that the measurement of ER-β in BC patients may help predict tamoxifen and anastrozole responsiveness in the neoadjuvant setting. These effects of hormonal treatment appear to be dependent on the ratio of ER-α/ER-β expression., Trial Registration: Current Controlled Trials ISRCTN89801719.
- Published
- 2013
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49. Short-term anastrozole therapy reduces Ki-67 and progesterone receptor expression in invasive breast cancer: a prospective, placebo-controlled, double-blind trial.
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Mattar A, Logullo AF, Facina G, Nonogaki S, Soares FA, and Gebrim LH
- Subjects
- Adult, Aged, Aged, 80 and over, Anastrozole, Breast Neoplasms chemistry, Breast Neoplasms pathology, Double-Blind Method, Female, Humans, Immunohistochemistry, Middle Aged, Prospective Studies, Tamoxifen therapeutic use, Antineoplastic Agents, Hormonal therapeutic use, Aromatase Inhibitors therapeutic use, Breast Neoplasms drug therapy, Ki-67 Antigen analysis, Nitriles therapeutic use, Receptors, Progesterone analysis, Triazoles therapeutic use
- Abstract
Purpose: The objective of this study was to compare Ki-67, Bcl-2, Bax, Bak, ER, and PgR expression in postmenopausal women with ER-positive invasive breast cancer (IBC) before and after short-term hormone therapy (HT) with either tamoxifen or anastrozole in order to identify a possible biomarker profile associated with hormone resistance., Methods: Fifty-eight patients with palpable IBC were assigned to receive neoadjuvant therapy with either anastrozole, placebo, or tamoxifen for 26 days prior to surgery. Tissue microarray blocks were constructed from pre- and post-treatment biopsy samples and used for immunohistochemical analysis. Biomarker (Ki-67, Bcl-2, Bax, Bak, ER, and PgR) levels were assessed semiquantitatively using the Allred score. A statistical analysis was performed using general estimating equations (GEE) and analysis of variance (ANOVA) with a significance level of 0.05., Results: There was a significant reduction in PgR scores from baseline (mean, 4.22) to post-treatment (mean, 1.94) in the anastrozole group, but only a non-significant trend toward an increase in PgR scores was found in the tamoxifen group. There was a significant reduction in Ki-67 scores from baseline (mean, 3.61) to post-treatment (mean, 2.56) in the anastrozole group (P = 0.01), but only a non-significant trend toward a reduction in Ki-67 scores was found in the tamoxifen group., Conclusions: There was a significant reduction in PgR and Ki-67 expression in the group treated with anastrozole. In the present study, the short-term HT was not associated with changes in apoptosis-related protein levels, regardless the type of drug used.
- Published
- 2011
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50. A case report of male breast cancer in a very young patient: what is changing?
- Author
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Madeira M, Mattar A, Passos RJ, Mora CD, Mamede LH, Kishino VH, Torres TZ, de Sá AF, dos Santos RE, and Gebrim LH
- Subjects
- Adult, Breast Neoplasms, Male therapy, Carcinoma, Ductal, Breast therapy, Combined Modality Therapy, Fatal Outcome, Fertility, Humans, Male, Mammography, Risk Factors, Breast Neoplasms, Male diagnosis, Carcinoma, Ductal, Breast diagnosis
- Abstract
Male breast cancer accounts for 1% of all breast cancer cases, and men tend to be diagnosed at an older age than women (mean age is about 67 years). Several risk factors have been identified, such as genetic and hormonal abnormalities. The present study reported the case of a 25-year-old man who was diagnosed with an advanced invasive ductal carcinoma; however, he did not have any important risk factors. Even though more data is emerging about this disease, more efforts to understand risk factors, treatment options and survival benefits are needed. In this case, we discussed the risk factors as well as the impaired fertility associated with breast cancer therapies.
- Published
- 2011
- Full Text
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