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1.
Clin. transl. oncol. (Print) ; 25(1): 151-159, ene. 2023.
Artigo em Inglês | IBECS | ID: ibc-215829

RESUMO

Background Adherence to clinical practice guidelines improves outcomes for patients with breast cancer. However, their implementation may not be feasible in low- and middle-income countries. This study aimed to evaluate physicians’ adherence, attitudes, and barriers towards the Colima Consensus, which is the Mexican national breast cancer clinical practice guideline. Methods A cross-sectional, 31-item survey was e-mailed to Consensus attendees and members of the Mexican Society of Oncology and Mexican Mastology Association. Descriptive statistics, univariate, and multivariate analysis were used to analyze the associations between participants’ characteristics, adherence, attitudes, and barriers. Result Of 439 respondents, 78% percent adhered to Consensus recommendations and 94% believed it was applicable to their clinical practice. Forty percent reported using the Consensus as their sole breast cancer guideline. This was associated with being a surgical oncologist (OR 3.3, 95% CI 2.0–5.3) and practicing at a public hospital (OR 2.1, 95% CI 1.2–3.7). The most common barriers to adherence were lack of resources and logistical problems. Regarding attitudes towards the Consensus, 90% considered it a good educational tool, 89% considered it a reliable source of information, and 90% thought it improved quality of care. Conclusions We showed high levels of adherence and positive attitudes towards the Colima Consensus, with a significant proportion of physicians using it as their only guideline. Lack of resources and logistical issues were the main barriers to adherence. Our results highlight the relevance of local breast cancer guidelines and suggest a need for the creation of resource-stratified guidelines (AU)


Assuntos
Humanos , Feminino , Atitude do Pessoal de Saúde , Padrões de Prática Médica , Neoplasias da Mama/terapia , Guias de Prática Clínica como Assunto , Fidelidade a Diretrizes , Inquéritos e Questionários , Estudos Transversais , México
2.
Clin Transl Oncol ; 25(1): 151-159, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35986133

RESUMO

BACKGROUND: Adherence to clinical practice guidelines improves outcomes for patients with breast cancer. However, their implementation may not be feasible in low- and middle-income countries. This study aimed to evaluate physicians' adherence, attitudes, and barriers towards the Colima Consensus, which is the Mexican national breast cancer clinical practice guideline. METHODS: A cross-sectional, 31-item survey was e-mailed to Consensus attendees and members of the Mexican Society of Oncology and Mexican Mastology Association. Descriptive statistics, univariate, and multivariate analysis were used to analyze the associations between participants' characteristics, adherence, attitudes, and barriers. RESULTS: Of 439 respondents, 78% percent adhered to Consensus recommendations and 94% believed it was applicable to their clinical practice. Forty percent reported using the Consensus as their sole breast cancer guideline. This was associated with being a surgical oncologist (OR 3.3, 95% CI 2.0-5.3) and practicing at a public hospital (OR 2.1, 95% CI 1.2-3.7). The most common barriers to adherence were lack of resources and logistical problems. Regarding attitudes towards the Consensus, 90% considered it a good educational tool, 89% considered it a reliable source of information, and 90% thought it improved quality of care. CONCLUSIONS: We showed high levels of adherence and positive attitudes towards the Colima Consensus, with a significant proportion of physicians using it as their only guideline. Lack of resources and logistical issues were the main barriers to adherence. Our results highlight the relevance of local breast cancer guidelines and suggest a need for the creation of resource-stratified guidelines.


Assuntos
Neoplasias da Mama , Médicos , Humanos , Feminino , Neoplasias da Mama/terapia , Estudos Transversais , México , Atitude do Pessoal de Saúde , Fidelidade a Diretrizes , Padrões de Prática Médica , Inquéritos e Questionários
3.
Ann Diagn Pathol ; 60: 151705, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33685748

RESUMO

The aim of this study was to investigate the expression of leptin (LEP) and its receptor (LEPR) in breast cancer tissue of postmenopausal women with different body mass indexes (BMI), as well as the relationship of this expression with the rate of recurrence free survival (RFS). Leptin and LEPR expression, determined by immunohistochemistry, were studied in breast cancer tissues of 154 patients. Qualitative and semi-quantitative analysis of protein expression was performed by the H-Score method, through the ImageJ's IHC Profiler software. Kaplan-Meier survival analysis and log-rank statistic were used to estimate RFS differences. Protein expression of LEP, was significantly higher in women with overweight or with obesity, when compared to women with normal BMI (P = 0.032 and P = 0.013, respectively). We also observed a significantly higher expression of LEPR in breast tumor cells of women with obesity (58.8%), when compared to women with normal BMI (32.7%) (P = 0.007). Five-year survival rate, regarding LEPR expression, was 82.4% when positive and 94% when negative (P = 0.024). In the Cox proportional-hazards regression model, LEPR expression represented a risk factor for disease recurrence after adjustment for confounding factors (HR = 4.67; 95% CI: 1.13-19.31; P = 0.033). In conclusion, postmenopausal women with obesity and breast cancer present higher LEP and LEPR expression in breast tumors, when compared to women with normal BMI. Independently from BMI, women with tumors LEPR positive have worst RFS, when compared to women with tumors LEPR negative.


Assuntos
Neoplasias da Mama , Leptina/metabolismo , Receptores para Leptina/metabolismo , Neoplasias da Mama/metabolismo , Feminino , Humanos , Recidiva Local de Neoplasia , Obesidade/complicações , Pós-Menopausa
4.
J Clin Pathol ; 2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-34083413

RESUMO

AIM: To analyse the fibronectin type III domain containing 5 (FNDC5)/irisin expression in tumour tissue of postmenopausal women presenting breast cancer and different body mass indexes (BMIs), proposing that obesity deregulates the expression of FNDC5/irisin at the breast tumour level. In addition, we investigated if different breast cancer cell lines are capable to synthesise this protein. METHODS: A total of 150 postmenopausal women (50 with a normal BMI, 50 presenting overweight and 50 having obesity) diagnosed with operable breast cancer were included. FNDC5/irisin expression was determined by immunohistochemistry or by immunocytochemistry. Qualitative analysis of protein expression was performed by the H-Score method, through ImageJ's IHC Profiler software. Statistical analyses were carried out using STATA V.14.0 (Texas, USA); p value<0.05 was accepted as statistically significant. Statistical power of the study was >80% with a p<0.05. RESULTS: FNDC5/irisin expression in breast cancer tissue of postmenopausal women with obesity was significantly increased when compared with FNDC5/irisin expression in women with a normal BMI (p=0.001). Furthermore, three breast cancer cell lines studied were capable to synthesise and express FNDC5/irisin, being the BT-474 cell line the one that exhibited the highest intensity of expression. CONCLUSIONS: Our results confirm that women with breast cancer and obesity exhibit an increased irisin expression in their tumorous tissue compared with women with breast cancer and normal BMI. Likewise, in vitro breast cancer cell lines have the capacity to synthesise and express FNDC5/irisin, without any extracellular stimuli, however the microenvironment surrounding these cells in vivo participates in its regulation.

5.
Nat Commun ; 12(1): 2245, 2021 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-33854067

RESUMO

Breast cancer is a heterogeneous pathology, but the genomic basis of its variability remains poorly understood in populations other than Caucasians. Here, through DNA and RNA portraits we explored the molecular features of breast cancers in a set of Hispanic-Mexican (HM) women and compared them to public multi-ancestry datasets. HM patients present an earlier onset of the disease, particularly in aggressive clinical subtypes, compared to non-Hispanic women. The age-related COSMIC signature 1 was more frequent in HM women than in those from other ancestries. We found the AKT1E17K hotspot mutation in 8% of the HM women and identify the AKT1/PIK3CA axis as a potentially druggable target. Also, HM luminal breast tumors present an enhanced immunogenic phenotype compared to Asiatic and Caucasian tumors. This study is an initial effort to include patients from Hispanic populations in the research of breast cancer etiology and biology to further understand breast cancer disparities.


Assuntos
Neoplasias da Mama/etnologia , Neoplasias da Mama/etiologia , Hispânico ou Latino/genética , Americanos Mexicanos/genética , Adulto , Idoso , Neoplasias da Mama/metabolismo , Classe I de Fosfatidilinositol 3-Quinases/genética , Feminino , Humanos , Pessoa de Meia-Idade , Mutação , Proteínas Proto-Oncogênicas c-akt/genética , Sequenciamento do Exoma
6.
J Clin Pathol ; 74(9): 571-576, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32848015

RESUMO

AIM: To analyse the expression of adiponectin (ADIPOQ), and its receptors ADIPOR1 and ADIPOR2, in breast cancer tissue of postmenopausal women with different body mass indexes (BMIs). SUBJECTS AND METHODS: One hundred and fifty postmenopausal Mexican-Mestizo women with breast cancer were included. BMI was determined in each case. To carry out qualitative and semiquantitative assessments of protein expression by immunohistochemistry, the H-Score method was used, through ImageJ's IHC Profiler software. Statistical power of the study was >80% with a p<0.05. RESULTS: Fifty women had a normal BMI, 50 presented overweight and 50 had obesity. The expression of ADIPOQ in breast cancer tissue of postmenopausal woman with normal BMI was higher in comparison to women with overweight or with obesity (p=0.002 and p<0.001, respectively). Furthermore, the expression of ADIPOR1 in breast cancer tissue of postmenopausal women with normal BMI was significantly lower when compared with women with overweight or with obesity (p=0.005 and p<0.001, respectively). Meanwhile, the expression of ADIPOR2 in breast cancer tissue, in the cytoplasm, was similar in all groups studied. CONCLUSIONS: We found that women with overweight or obesity had a lower expression of ADIPOQ and a higher ADIPOR1 expression in breast cancer tissue, when compared with women with a normal BMI.


Assuntos
Adiponectina/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Obesidade/complicações , Receptores de Adiponectina/metabolismo , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/complicações , Feminino , Humanos , México , Pessoa de Meia-Idade , Pós-Menopausa
7.
Front Oncol ; 10: 572954, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33194675

RESUMO

Studies have suggested a potential role of somatic mitochondrial mutations in cancer development. To analyze the landscape of somatic mitochondrial mutation in breast cancer and to determine whether mitochondrial DNA (mtDNA) mutational burden is correlated with overall survival (OS), we sequenced whole mtDNA from 92 matched-paired primary breast tumors and peripheral blood. A total of 324 germline variants and 173 somatic mutations were found in the tumors. The most common germline allele was 663G (12S), showing lower heteroplasmy levels in peripheral blood lymphocytes than in their matched tumors, even reaching homoplasmic status in several cases. The heteroplasmy load was higher in tumors than in their paired normal tissues. Somatic mtDNA mutations were found in 73.9% of breast tumors; 59% of these mutations were located in the coding region (66.7% non-synonymous and 33.3% synonymous). Although the CO1 gene presented the highest number of mutations, tRNA genes (T,C, and W), rRNA 12S, and CO1 and ATP6 exhibited the highest mutation rates. No specific mtDNA mutational profile was associated with molecular subtypes of breast cancer, and we found no correlation between mtDNA mutational burden and OS. Future investigations will provide insight into the molecular mechanisms through which mtDNA mutations and heteroplasmy shifting contribute to breast cancer development.

8.
Sci Rep ; 10(1): 13146, 2020 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-32753692

RESUMO

Breast cancer is the most commonly diagnosed neoplasm in women worldwide with a well-recognized heterogeneous pathology, classified into four molecular subtypes: Luminal A, Luminal B, HER2-enriched and Basal-like, each one with different biological and clinical characteristics. Long non-coding RNAs (lncRNAs) represent 33% of the human transcriptome and play critical roles in breast carcinogenesis, but most of their functions are still unknown. Therefore, cancer research could benefit from continued exploration into the biology of lncRNAs in this neoplasm. We characterized lncRNA expression portraits in 74 breast tumors belonging to the four molecular subtypes using transcriptome microarrays. To infer the biological role of the deregulated lncRNAs in the molecular subtypes, we performed co-expression analysis of lncRNA-mRNA and gene ontology analysis. We identified 307 deregulated lncRNAs in tumor compared to normal tissue and 354 deregulated lncRNAs among the different molecular subtypes. Through co-expression analysis between lncRNAs and protein-coding genes, along with gene enrichment analysis, we inferred the potential function of the most deregulated lncRNAs in each molecular subtype, and independently validated our results taking advantage of TCGA data. Overexpression of the AC009283.1 was observed in the HER2-enriched subtype and it is localized in an amplification zone at chromosome 17q12, suggesting it to be a potential tumorigenic lncRNA. The functional role of lncRNA AC009283.1 was examined through loss of function assays in vitro and determining its impact on global gene expression. These studies revealed that AC009283.1 regulates genes involved in proliferation, cell cycle and apoptosis in a HER2 cellular model. We further confirmed these findings through ssGSEA and CEMITool analysis in an independent HER2-amplified breast cancer cohort. Our findings suggest a wide range of biological functions for lncRNAs in each breast cancer molecular subtype and provide a basis for their biological and functional study, as was conducted for AC009283.1, showing it to be a potential regulator of proliferation and apoptosis in the HER2-enriched subtype.


Assuntos
Apoptose , Neoplasias da Mama/metabolismo , Proliferação de Células , Cromossomos Humanos Par 17 , RNA Longo não Codificante/biossíntese , Receptor ErbB-2/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Cromossomos Humanos Par 17/genética , Cromossomos Humanos Par 17/metabolismo , Feminino , Humanos , Células MCF-7 , RNA Longo não Codificante/genética , Receptor ErbB-2/genética
9.
PLoS One ; 15(3): e0228884, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32160201

RESUMO

OBJECTIVE: To evaluate the change in adjuvant therapeutic decision in a cohort of young women with breast cancer discussed by a multidisciplinary team, before and after EndoPredict testing. PATIENTS AND METHODS: 99 premenopausal women with hormone receptor-positive, HER2-negative, T1-T2, and N0-N1 breast cancer were included. Clinicopathological characteristics were recorded and cases were presented in a multidisciplinary tumor board. Consensual therapeutic decisions before and after EndoPredict results were registered. Medical records were reviewed at six-month follow-up to determine physicians' adherence to therapeutic recommendations. Pearson chi-square and McNemar's tests were used to analyze differences between groups and changes in treatment recommendations, respectively. RESULTS: Median age at diagnosis was 43 years. The most frequent tumor size was pT2 (53.5%) and 27% of patients had 1-3 positive lymph nodes. 46% of patients had a low-risk EPclin result. Nodal status and tumor grade were significantly associated with EPclin result (p < .00001 and p = .0110, respectively), while Ki67 levels and age ≤40 years were not. A change in chemotherapy decision was registered in 19.2% of patients (p = .066), with the greatest impact in de-escalation (9% net reduction). A change in chemotherapy or endocrine therapy regimen was suggested in 19% and 20% of cases, respectively, after EPclin results were available. A significant difference was found in the median EPclin score between patients with a low- vs. high-intensity chemotherapy and endocrine therapy regimen recommendation (p = 0.049 and p = 0.0001, respectively). Tumor board treatment recommendation adherence with the EndoPredict result was 95% and final treatment adherence to EPclin result was 93%. CONCLUSIONS: The EndoPredict test successfully assisted the clinical decision-making process in premenopausal patients, with a clinically significant change in overall decision-making, with the greatest impact seen in chemotherapy reduction, and a high rate of therapeutic adherence.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante/métodos , Tomada de Decisão Clínica , Pré-Menopausa , Transcriptoma , Adulto , Neoplasias da Mama/metabolismo , Estudos de Coortes , Tomada de Decisões , Feminino , Humanos , México , Pessoa de Meia-Idade , Gradação de Tumores
10.
Rev. senol. patol. mamar. (Ed. impr.) ; 32(1): 32-36, ene.-mar. 2019. ilus
Artigo em Inglês | IBECS | ID: ibc-187031

RESUMO

Secretory breast carcinoma was first described by McDivitt and Stewart in 1966, who reported seven cases of this tumoural strain in children and therefore named it "juvenile carcinoma". However, a couple of decades later, Tavassoli and Norris reported a series of 19 cases and found that most occurred in adults, and therefore they proposed changing its name to "secretory carcinoma." Since then, approximately 100 cases have been reported in the world literature. We present two cases treated with total mastectomy and sentinel node biopsy with excellent outcome. To our knowledge, only a few cases have been reported in Latin American patients


El carcinoma secretor dela mama fue inicialmente descrito por McDivitt y Stewartin en 1966, en su artículo, siete casos de este tipo de tumor se presentaron en niños, por lo tanto, se le asignó el nombre de "carcinoma Juvenil", pero un par de décadas después Tavassoli y Norris encontraron en su serie de 19 casos, que la mayoría eran adultos, y así propusieron cambiar el nombre a Carcinoma secretor. Desde ese momento aproximadamente 100 casos han sido reportados en la literatura. Nosotros presentamos dos casos tratados con mastectomía y ganglio centinela, con excelente pronóstico. Hasta donde sabemos, esta patología se ha reportado escasamente en pacientes latino americanos


Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Neoplasias da Mama/patologia , Mastectomia/métodos , Biópsia de Linfonodo Sentinela/métodos , Invasividade Neoplásica/patologia
11.
Mol Oncol ; 13(4): 909-927, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30648789

RESUMO

Triple negative breast cancer (TNBC) represents an aggressive phenotype with poor prognosis compared with ER, PR, and HER2-positive tumors. TNBC is a heterogeneous disease, and gene expression analysis has identified seven molecular subtypes. Accumulating evidence demonstrates that long non-coding RNA (lncRNA) are involved in regulation of gene expression and cancer biology, contributing to essential cancer cell functions. In this study, we analyzed the expression profile of lncRNA in TNBC subtypes from 156 TNBC samples, and then characterized the functional role of LncKLHDC7B (ENSG00000226738). A total of 710 lncRNA were found to be differentially expressed between TNBC subtypes, and a subset of these altered lncRNA were independently validated. We discovered that LncKLHDC7B (ENSG00000226738) acts as a transcriptional modulator of its neighboring coding gene KLHDC7B in the immunomodulatory subtype. Furthermore, LncKLHDC7B knockdown enhanced migration and invasion, and promoted resistance to cellular death. Our findings confirmed the contribution of LncKLHDC7B to induction of apoptosis and inhibition of cell migration and invasion, suggesting that TNBC tumors with enrichment of LncKLHDC7B may exhibit distinct regulatory activity, or that this may be a generalized process in breast cancer. Additionally, in silico analysis confirmed for the first time that the low expression of KLHDC7B and LncKLHDC7B is associated with poor prognosis in patients with breast cancer.


Assuntos
Apoptose/genética , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica , Imunomodulação , RNA Longo não Codificante/genética , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/imunologia , Linhagem Celular Tumoral , Regulação para Baixo/genética , Inativação Gênica , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Invasividade Neoplásica , Fenótipo , RNA Longo não Codificante/metabolismo , Neoplasias de Mama Triplo Negativas/classificação , Neoplasias de Mama Triplo Negativas/patologia , Regulação para Cima/genética
12.
Ginecol. obstet. Méx ; 87(1): 60-66, ene. 2019. graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1154271

RESUMO

Resumen ANTECEDENTES: La enfermedad de Paget mamaria es una alteración poco frecuente, caracterizada por cambios en el área del pezón-areola, que puede asociarse con carcinoma de mama in situ o invasor. CASO CLÍNICO: Paciente de 69 años, con lesión mamaria de tres años de evolución, cambios en la coloración del pezón y descamación, acompañados de prurito, de aspecto eritematoso y escamoso en el área del pezón-areola izquierda, con retracción del pezón; se obtuvo una biopsia del área del pezón-areola. El estudio de patología reportó células neoplásicas grandes, con infiltración a la epidermis, aisladas o en pequeños grupos, con citoplasma claro, vacuolado, núcleo agrandado y nucléolo prominente, característico de la enfermedad de Paget mamaria. El estudio de inmunohistoquímica reportó positividad para CK7 y HER2, y negatividad para p53 a células neoplásicas, con lo que se estableció el diagnóstico definitivo de enfermedad de Paget mamaria. La mastografía no mostró alteraciones y la mastectomía reportó carcinoma intraductal. CONCLUSIÓN: El conocimiento de la enfermedad de Paget mamaria tiene importancia clínica, puesto que representa una afección poco frecuente, que debe considerarse en el diagnóstico diferencial de lesiones benignas del complejo areola-pezón.


Abstract BACKGROUND: The Paget´s disease mammary is an uncommon malignancy that presents with changes in the nipple-areolar region that may be associated with an underlying breast cancer. CLINICAL CASE: A 69-year-old patient with a breast lesion of three years of evolution, changes in nipple, characterized by coloration and scaling, pruritus, with an erythematous and scaly appearance in the nipple-areola left region, and nipple retraction. A biopsy of the nipple-areola was obtained. The Pathology service reported large neoplastic cells, with infiltration to the epidermis, isolated or in small groups, with clear cytoplasm, vacuolated, enlarged nucleus and prominent nucleolus, characteristic of Paget's disease mammary. The immunohistochemistry study reported positivity for CK7 and HER2, and negativity for p53 to neoplastic cells, which established the definitive diagnosis of Paget's disease of the breast. The mammography was normal and the mastectomy reported intraductal carcinoma. CONCLUSION: The knowledge of mammary Paget's disease is of clinical importance, since it represents a rare condition, which must be considered in the differential diagnosis of benign lesions of the areola-nipple complex.

13.
Sci Rep ; 8(1): 12252, 2018 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-30115973

RESUMO

Triple-negative breast cancer (TNBC) is a heterogeneous and aggressive neoplasia lacking the expression of hormonal receptors and human epidermal growth factor receptor-2. Accumulating evidence has highlighted the importance of miRNAs dysregulation in the establishment of cancer programs, but the functional role of many miRNAs remains unclear. The description of miRNAs roles might provide novel strategies for treatment. In the present work, an integrated analysis of miRNA transcriptional landscape was performed (N = 132), identifying the significant down-modulation of miR-342-3p in TNBC, probably because of the aberrant activity of estrogen receptor, which serves as a transcription factor of the miRNA, as demonstrated by a siRNA-knockdown approach. The enhanced expression of miR-342-3p significantly decreased cell proliferation, viability and migration rates of diverse TN cells in vitro. Bioinformatic and functional analyses revealed that miR-342-3p directly targets the monocarboxylate transporter 1 (MCT1), which promotes lactate and glucose fluxes alteration, thus disrupting the metabolic homeostasis of tumor cells. Optical metabolic imaging assay defined a higher optical redox ratio in glycolytic cells overexpressing miR-342-3p. Furthermore, we found that hypoxic conditions and glucose starvation attenuate miR-342-3p expression, suggesting a crosstalk program between these metabolic factors. Consistently, miR-342-3p down-modulation is associated with an increased MCT1 expression level and glycolytic score in human triple negative tumors. Overall, we described for the first time the regulatory activity of miR-342-3p on relevant metabolic carcinogenic pathways in TN breast cancers.


Assuntos
Carcinogênese , Regulação Neoplásica da Expressão Gênica/genética , MicroRNAs/genética , Transportadores de Ácidos Monocarboxílicos/genética , Simportadores/genética , Neoplasias de Mama Triplo Negativas/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Sobrevivência Celular/genética , Glucose/metabolismo , Glicólise , Homeostase/genética , Humanos , Ácido Láctico/metabolismo , Fosforilação Oxidativa , Receptores de Estrogênio/metabolismo , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo
14.
Sci Rep ; 6: 34504, 2016 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-27703260

RESUMO

Deregulated expression of microRNAs has been associated with angiogenesis. Studying the miRNome of locally advanced breast tumors we unsuspectedly found a dramatically repression of miR-204, a small non-coding RNA with no previous involvement in tumor angiogenesis. Downregulation of miR-204 was confirmed in an independent cohort of patients and breast cancer cell lines. Gain-of-function analysis indicates that ectopic expression of miR-204 impairs cell proliferation, anchorage-independent growth, migration, invasion, and the formation of 3D capillary networks in vitro. Likewise, in vivo vascularization and angiogenesis were suppressed by miR-204 in a nu/nu mice model. Genome-wide profiling of MDA-MB-231 cells expressing miR-204 revealed changes in the expression of hundred cancer-related genes. Of these, we focused on the study of pro-angiogenic ANGPT1 and TGFßR2. Functional analysis using luciferase reporter and rescue assays confirmed that ANGPT1 and TGFßR2 are novel effectors downstream of miR-204. Accordingly, an inverse correlation between miR-204 and ANGPT1/TGFßR2 expression was found in breast tumors. Knockdown of TGFßR2, but not ANGPT1, impairs cell proliferation and migration whereas inhibition of both genes inhibits angiogenesis. Taken altogether, our findings reveal a novel role for miR-204/ANGPT1/TGFßR2 axis in tumor angiogenesis. We propose that therapeutic manipulation of miR-204 levels may represent a promising approach in breast cancer.


Assuntos
Angiopoietina-1/biossíntese , Neoplasias da Mama/irrigação sanguínea , Neoplasias da Mama/metabolismo , MicroRNAs/biossíntese , Proteínas de Neoplasias/biossíntese , Neovascularização Patológica/metabolismo , Proteínas Serina-Treonina Quinases/biossíntese , RNA Neoplásico/biossíntese , Receptores de Fatores de Crescimento Transformadores beta/biossíntese , Angiopoietina-1/genética , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Feminino , Humanos , Células MCF-7 , MicroRNAs/genética , Proteínas de Neoplasias/genética , Neovascularização Patológica/genética , Neovascularização Patológica/patologia , Neovascularização Patológica/terapia , Proteínas Serina-Treonina Quinases/genética , RNA Neoplásico/genética , Receptor do Fator de Crescimento Transformador beta Tipo II , Receptores de Fatores de Crescimento Transformadores beta/genética
15.
Pathol Res Pract ; 212(11): 1034-1038, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27667558

RESUMO

OBJECTIVE: To show the incidence, as well as the clinical and histopathological characteristics, of patients diagnosed with mammary salivary gland-like carcinomas at our institution. MATERIALS AND METHODS: A retrospective study was conducted in all women diagnosed with breast cancer at our institution from January 2005 to February 2016. Patients with diagnosis of salivary gland-like breast carcinomas were included. RESULTS: In this period, 6384 patients were diagnosed with breast cancer at our institution; salivary gland-like carcinomas were found in 7 patients (0.1%), adenoid cystic carcinoma was diagnosed in 5 patients (0.07%), acinic cell carcinoma in 1 patient (0.015%) and mucoepidermoid carcinoma in 1 patient (0.015%). The triple-negative subtype was found in all of the tumors. Median follow-up was 66.3 months (range, 1-108 months). No patient developed local or distant recurrence. CONCLUSIONS: Salivary gland-like breast tumors are extremely rare. We found a global incidence of 0.1%. Adenoid cystic, acinic cell and mucoepidermoid carcinomas were the three histologic types diagnosed. Although the triple-negative subtype is mainly found, good prognosis is expected.


Assuntos
Carcinoma de Células Acinares/patologia , Carcinoma Adenoide Cístico/patologia , Carcinoma Mucoepidermoide/patologia , Neoplasias de Mama Triplo Negativas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
16.
Case Rep Oncol Med ; 2016: 7481569, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27403361

RESUMO

Proliferating trichilemmal tumors (PTTs) are benign adnexal skin neoplasms that arise from the outer root sheath of the hair follicle. These tumors are most commonly observed on the scalp and occur, most of the time, in elderly women. Malignant transformation of these neoplasms is a rare event; less than 50 cases have been reported in the English medical literature. We present the case of a 39-year-old Hispanic woman with a tumor located on the skin of one of her breasts that in her third surgical procedure the histologic examination revealed the presence of a malignant proliferating trichilemmal tumor (MPTT). Furthermore, a review of the medical literature and a discussion of the clinical and pathologic features of this rare entity are provided.

17.
Case Rep Pathol ; 2016: 3603262, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28105378

RESUMO

Benign and malignant pathology can develop in ectopic axillary breast tissue, such as fibroadenomas, phyllodes tumors, and breast cancer. We present a rare case of an asymptomatic 43-year-old woman with an axillary nodule which was identified during screening mammography within ectopic axillary breast tissue, initially considered as a suspicious lymph node. Radiologic studies were considered as Breast Imaging-Reporting Data System (BI-RADS) 4. A hyperdense, lobular, and well-circumscribed nodule was identified in mammogram while the nodule by ultrasound (US) was hypoechoic with indistinct microlobular margins, without vascularity by Doppler, and measuring 1.26 × 1 cm. Core-needle biopsy reported a fibroepithelial neoplasm. The patient was submitted to local wide-needle excision located in intraoperative radiography of the surgical specimen and margin evaluation. Final histopathological study reported a 1.8 × 1.2 cm benign phyllodes tumor, with irregular, pushing, and clear wide margins within normal ectopic breast tissue. The patient without surgical complications continued annual screening without recurrence during a follow-up that took place 24 months later.

18.
Iran J Pathol ; 11(4): 399-408, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28855932

RESUMO

BACKGROUND: Phyllodes tumor (PT) of the breast in Hispanic patients is more frequently reported with large tumors and with more borderline/malignant subtypes compared with other populations. The objective of this study was to describe characteristics of patients with PT and to identify differences among subtypes in a Mexican population. METHODS: A retrospective study was conducted on patients with PT. Sociodemographic, histopathologic, and treatment characteristics were compared among subtypes, including only surgically treated cases due the complete surgical-specimen study requirement for appropriate WHO classification. RESULTS: During 10 years, 346 PT were diagnosed; only 307 were included (305 patients), with a mean age of 41.7 yr. Self-detected lump took place in 91.8%, usually discovered 6 months previously, with median tumor size of 4.5 cm. Local wide excisions were done in 213 (69.8%) and mastectomies in 92 (30.1%). Immediate breast reconstruction took place in 38% and oncoplastic procedures in 23%. PT were classified as benign in 222 (72.3%) cases, borderline in 50 (16.2%), and malignant in 35 (11.4%), with pathological tumor size of 4.2, 5.4, and 8.7 cm, respectively (P<0.001). Patients with malignant PT were older (48 yr), with more diabetics (14.3%), less breastfeeding (37.1%), more smokers (17.1%), with more postmenopausal cases (42.9%), and older age at menopause (51.5 years) compared with the remaining subtypes (P<0.05). Relapse occurred in 8.2% of patients with follow-up. CONCLUSION: In comparison with other Hispanic publications, these Mexican patients had similar age, with smaller tumors, modestly higher benign PT, fewer malignant PT, and lower documented relapse cases.

20.
Cir Cir ; 82(2): 129-41, 2014.
Artigo em Espanhol | MEDLINE | ID: mdl-25312311

RESUMO

BACKGROUND: Sentinel lymph node biopsy in patients with ductal carcinoma in situ still controversial, with positive lymph node in range of 1.4-12.5% due occult invasive breast carcinoma in surgical specimen. OBJECTIVE: To know the frequency of sentimel node metastases in patients with ductal carcinoma in situ, identify differences between positive and negative cases. METHODS: Retrospective study of patients with ductal carcinoma in situ treated with sentinel lymph node biopsy because mastectomy indication, palpable tumor, radiological lesion = 5 cm, non-favorable breast-tumor relation and/or patients whom surgery could affect lymphatic flow drainage. RESULTS: Of 168 in situ carcinomas, 50 cases with ductal carcinoma in situ and sentinel lymph node biopsy were included, with a mean age of 51.6 years, 30 (60%) asymptomatic. The most common symptoms were palpable nodule (18%), nipple discharge (12%), or both (8%). Microcalcifications were common (72%), comedonecrosis pattern (62%), grade-2 histology (44%), and 28% negative hormonal receptors. Four (8%) cases had intra-operatory positive sentinel lymph node and one patient at final histo-pathological study (60% micrometastases, 40% macrometastases), all with invasive carcinoma in surgical specimen. Patients with intra-operatory positive sentinel lymph node where younger (44.5 vs 51 years), with more palpable tumors (50% vs 23.1%), and bigger (3.5 vs 2 cm), more comedonecrosis pattern (75% vs 60.8%), more indifferent tumors (75% vs 39.1%), and less cases with hormonal receptors (50% vs 73.9%), compared with negative sentinel lymph node cases, all these differences without statistic significance. CONCLUSIONS: One of each 12 patients with ductal carcinoma in situ had affection in sentinel lymph node, so we recommend continue doing this procedure to avoid second surgeries due the presence of occult invasive carcinoma.


Antecedentes: en pacientes con carcinoma ductal in situ la biopsia de ganglio centinela es motivo de controversia porque se reportan ganglios positivos en 1.4-12.5% debido al carcinoma invasor oculto en la pieza quirúrgica. Objetivo: conocer la frecuencia de metástasis en ganglio centinela en pacientes con carcinoma ductal in situ e identificar las diferencias entre los casos positivos y negativos. Material y métodos: estudio retrospectivo, transversal, analítico de pacientes con carcinoma ductal in situ a quienes se realizó una biopsia de ganglio centinela por requerir mastectomía, tener un tumor palpable, lesión radiológica = 5 cm, inadecuada relación mama-tumor o porque la escisión pudiera afectar el flujo linfático. Resultados: de 168 carcinomas in situ, se incluyeron 50 casos con carcinoma ductal in situ y biopsia de ganglio centinela, de pacientes con edad promedio de 51.6 años, 30 (60%) de ellas asintomáticas. Los signos reportados fueron: nódulo palpable (18%), secreción por el pezón (12%) o ambos (8%). Predominaron las microcalcificaciones (72%), comedonecrosis (62%) y grado histológico -2 (44%) con 28% de receptores hormonales negativos. En el estudio transoperatorio 4 (8%) pacientes tuvieron ganglio centinela positivo y un caso en estudio histopatológico definitivo (60% micrometástasis, 40% macrometástasis), todos con carcinoma invasor en la pieza quirúrgica. Las pacientes con ganglio centinela transoperatorio positivo eran más jóvenes (44.5 vs 51 años), con más tumores palpables (50 vs 23.1%), más grandes (3.5 vs 2 cm), más comedonecrosis (75 vs 60.8%), más indiferenciados (75% vs 39.1%) y menos receptores hormonales (50 vs 73.9%), que las que tenían ganglio centinela negativo, sin que estas diferencias tuvieran significación estadística. Conclusiones: puesto que 1 de cada 12 pacientes con carcinoma ductal in situ tiene afectación ganglionar en el ganglio centinela, se recomienda seguir tomando la biopsia para evitar segundas cirugías por un carcinoma invasor oculto.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/secundário , Metástase Linfática/diagnóstico , Biópsia de Linfonodo Sentinela , Adulto , Axila , Calcinose/diagnóstico por imagem , Carcinoma Intraductal não Infiltrante/diagnóstico , Carcinoma Lobular/diagnóstico , Carcinoma Lobular/secundário , Estrogênios , Feminino , Humanos , Excisão de Linfonodo , Mamografia , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Neoplasias Hormônio-Dependentes/diagnóstico , Neoplasias Hormônio-Dependentes/secundário , Fluido do Aspirado de Mamilo , Progesterona , História Reprodutiva
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