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1.
Hum Mutat ; 42(3): 290-299, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33326660

RESUMEN

The current study aimed to identify new breast and/or ovarian cancer predisposition genes. For that, whole-exome sequencing (WES) was performed in the germline DNA of 52 non-BRCA1/BRCA2/TP53 mutation carrier women at high-risk for hereditary breast and ovarian cancer (HBOC). All variants were classified using information from population and disease specific databases, in silico prediction tools and the American College of Medical Genetics and Genomics (ACMG) criteria. Loss of heterozygosity (LOH) of tumor samples and segregation analyses were performed whenever possible. The variants identified were investigated in a second, independent cohort of 17 BC cases. Pathogenic/Likely Pathogenic variants were identified in known cancer genes such as CHEK2, MUTYH, PMS2, and RAD51C. Rare and potentially pathogenic variants were identified in DNA repair genes (FAN1, POLQ, and RAD54L) and other cancer-related genes such as DROSHA and SLC34A2. Interestingly, the variant c.149T>G in the FAN1 gene was identified in two unrelated families, and exhibited LOH in the tumor tissue of one of them. In conclusion, this is the largest Brazilian WES study involving families at high-risk for HBOC which has brought novel insights into the role of potentially new genetic risk factors for hereditary breast and ovarian cancer.


Asunto(s)
Neoplasias de la Mama , Síndrome de Cáncer de Mama y Ovario Hereditario , Neoplasias Ováricas , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias de la Mama/patología , Femenino , Genes BRCA2 , Predisposición Genética a la Enfermedad , Mutación de Línea Germinal , Síndrome de Cáncer de Mama y Ovario Hereditario/genética , Humanos , Pérdida de Heterocigocidad , Mutación , Neoplasias Ováricas/genética , Secuenciación del Exoma
2.
Genet Mol Biol ; 43(2): e20190072, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32453342

RESUMEN

Specific pathogenic mutations associated with breast cancer development can vary between ethnical groups. One example is BRCA1 c.5266dupC that was first described as a founder mutation in the Ashkenazi Jewish population, but was later also found in other populations. In Brazil, this mutation corresponds to 20% of pathogenic BRCA1 variants reported. Our objective was to investigate the haplotype component of a group of Brazilian families who inherited c.5266dupC in the BRCA1 gene and to verify the ancestry contribution from European, African, and Amerindian origins. Fourteen probands carrying c.5266dupC and 16 relatives (carriers and non-carriers) were investigated. The same haplotype was observed segregating within all the families analyzed, revealing no recombinants in a region of 0.68 Mb. Ancestry analysis demonstrated that the European component was predominant among probands. The BRCA1 c.5266dupC analysis indicates that there was a founder effect in the Brazilian population.

3.
Asian Pac J Cancer Prev ; 20(6): 1655-1660, 2019 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-31244284

RESUMEN

The identification of families at-risk for hereditary breast cancer (BC) is important because affected individuals present a much higher cancer risk than the general population. The aim of this study was to identify the most important factors associated with the presence of a pathogenic BRCA1/BRCA2 mutation. Family history (FH), histopathological and immunohistochemical characteristics were compared among BC women with pathogenic BRCA1/BRCA2 variants; VUSs in BRCA1/BRCA2; BRCA1/BRCA2 WT and sporadic BC. The most significative differences observed concerned the molecular subtype of the tumors, age at cancer diagnosis and FH of cancer. The presence of bilateral breast cancer (BBC), number of BC cases and the presence of ovarian cancer (OC) increased (respectively) 5.797, 5.033 and 4.412 times the risk of being a BRCA1/BRCA2 mutation carrier. Besides, women with BRCA1 or BRCA2 mutations presented different tumor and FH profiles. The main characteristics associated with a BRCA1 mutation were triple negativity (OR: 17.31), BBC history (OR: 4.96) and occurrence of OC (OR: 4.32). There were no major discerning components associated with BRCA2 mutations. Thus, we conclude that tumor pathology and FH of cancer might be considered together at the time of genetic testing mainly in countries where access to genetic testing is still restricted.


Asunto(s)
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias de la Mama/clasificación , Neoplasias de la Mama/patología , Predisposición Genética a la Enfermedad , Mutación , Neoplasias Ováricas/patología , Adulto , Brasil/epidemiología , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/genética , Femenino , Estudios de Seguimiento , Pruebas Genéticas , Humanos , Incidencia , Persona de Mediana Edad , Neoplasias Ováricas/epidemiología , Neoplasias Ováricas/genética , Pronóstico
4.
Cancer Med ; 6(12): 3014-3024, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29055968

RESUMEN

One of the challenges for Latin American countries is to include in their healthcare systems technologies that can be applied to hereditary cancer detection and management. The aim of the study is to create and validate a questionnaire to identify individuals with possible risk for hereditary cancer predisposition syndromes (HCPS), using different strategies in a Cancer Prevention Service in Brazil. The primary screening questionnaire (PSQ) was developed to identify families at-risk for HCPS. The PSQ was validated using discrimination measures, and the reproducibility was estimated through kappa coefficient. Patients with at least one affirmative answer had the pedigree drawn using three alternative interview approaches: in-person, by telephone, or letter. Validation of these approaches was done. Kappa and intraclass correlation coefficients were used to analyze data's reproducibility considering the presence of clinical criteria for HCPS. The PSQ was applied to a convenience sample of 20,000 women of which 3121 (15.6%) answered at least one affirmative question and 1938 had their pedigrees drawn. The PSQ showed sensitivity and specificity scores of 94.4% and 75%, respectively, and a kappa of 0.64. The strategies for pedigree drawing had reproducibility coefficients of 0.976 and 0.850 for the telephone and letter approaches, respectively. Pedigree analysis allowed us to identify 465 individuals (24.0%) fulfilling at least one clinical criterion for HCPS. The PSQ fulfills its function, allowing the identification of HCPS at-risk families. The use of alternative screening methods may reduce the number of excluded at-risk individuals/families who live in locations where oncogenetic services are not established.


Asunto(s)
Neoplasias de la Mama/genética , Neoplasias Colorrectales/genética , Tamizaje Masivo/métodos , Neoplasias Ováricas/genética , Encuestas y Cuestionarios , Adolescente , Adulto , Edad de Inicio , Anciano , Brasil/epidemiología , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/epidemiología , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/epidemiología , Correspondencia como Asunto , Femenino , Predisposición Genética a la Enfermedad , Herencia , Humanos , Entrevistas como Asunto , Persona de Mediana Edad , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/epidemiología , Linaje , Fenotipo , Vigilancia de la Población , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Medición de Riesgo , Factores de Riesgo , Teléfono , Adulto Joven
5.
Oncotarget ; 7(49): 80465-80481, 2016 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-27741520

RESUMEN

BACKGROUND: There are very few data about the mutational profile of families at-risk for hereditary breast and ovarian cancer (HBOC) from Latin America (LA) and especially from Brazil, the largest and most populated country in LA. RESULTS: Of the 349 probands analyzed, 21.5% were BRCA1/BRCA2 mutated, 65.3% at BRCA1 and 34.7% at BRCA2 gene. The mutation c.5266dupC (former 5382insC) was the most frequent alteration, representing 36.7% of the BRCA1 mutations and 24.0% of all mutations identified. Together with the BRCA1 c.3331_3334delCAAG mutation, these mutations constitutes about 35% of the identified mutations and more than 50% of the BRCA1 pathogenic mutations. Interestingly, six new mutations were identified. Additionally, 39 out of the 44 pathogenic mutations identified were not previously reported in the Brazilian population. Besides, 36 different variants of unknown significance (VUS) were identified. Regarding ancestry, average ancestry proportions were 70.6% European, 14.5% African, 8.0% Native American and 6.8% East Asian. MATERIALS AND METHODS: This study characterized 349 Brazilian families at-risk for HBOC regarding their germline BRCA1/BRCA2 status and genetic ancestry. CONCLUSIONS: This is the largest report of BRCA1/BRCA2 assessment in an at-risk HBOC Brazilian population. We identified 21.5% of patients harboring BRCA1/BRCA2 mutations and characterized the genetic ancestry of a sample group at-risk for hereditary breast cancer showing once again how admixed is the Brazilian population. No association was found between genetic ancestry and mutational status. The knowledge of the mutational profile in a population can contribute to the definition of more cost-effective strategies for the identification of HBOC families.


Asunto(s)
Proteína BRCA1/genética , Proteína BRCA2/genética , Biomarcadores de Tumor/genética , Neoplasias de la Mama/genética , Mutación de Línea Germinal , Patrón de Herencia , Neoplasias Ováricas/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Brasil/epidemiología , Neoplasias de la Mama/etnología , Neoplasias de la Mama/patología , Análisis Mutacional de ADN , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Herencia , Humanos , Persona de Mediana Edad , Neoplasias Ováricas/etnología , Neoplasias Ováricas/patología , Linaje , Fenotipo , Medición de Riesgo , Factores de Riesgo , Adulto Joven
6.
Genet Mol Biol ; 39(2): 168-77, 2016 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-27192127

RESUMEN

The identification of families at-risk for hereditary cancer is extremely important due to the prevention potential in those families. However, the number of Brazilian genetic services providing oncogenetic care is extremely low for the continental dimension of the country and its population. Therefore, at-risk patients do not receive appropriate assistance. This report describes the creation, structure and management of a cancer genetics service in a reference center for cancer prevention and treatment, the Barretos Cancer Hospital (BCH). The Oncogenetics Department (OD) of BCH offers, free of charge, to all patients/relatives with clinical criteria, the possibility to perform i) genetic counseling, ii) preventive examinations and iii) genetic testing with the best quality standards. The OD has a multidisciplinary team and is integrated with all specialties. The genetic counseling process consists (mostly) of two visits. In 2014, 614 individuals (371 families) were seen by the OD. To date, over 800 families were referred by the OD for genetic testing. The support provided by the Oncogenetics team is crucial to identify at-risk individuals and to develop preventive and personalized behaviors for each situation, not only to the upper-middle class population, but also to the people whose only possibility is the public health system.

7.
Artículo en Inglés | MEDLINE | ID: mdl-26770289

RESUMEN

INTRODUCTION: Breast cancer (BC) is an important public health problem worldwide. In Brazil, breast cancer is the most frequently diagnosed tumor and the leading cause of cancer death in women. Hereditary cancer represents approximately 5 to 10 % of BC cases. Even outside the hereditary cancer context, the presence of polymorphisms acting as genetic modifiers may contribute to a better or worse prognosis. Not much is known about the hereditary BC epidemiology in Brazil or about the influence of polymorphisms on hereditary predisposition. OBJECTIVE: This study examined the role of five different polymorphisms in four groups of women with BC: Group 1: women with a germline mutation in the BRCA1/2 genes; Group 2: women with variants of uncertain significance in BRCA1/2 and Group 3: women with no mutations in BRCA1/2. PATIENTS AND METHODS: The women included in groups 1, 2 and 3 were patients from the Department of Oncogenetics of the Barretos Cancer Hospital who had undergone genetic testing because of a clinical suspicion of hereditary predisposition syndrome. The constitutive DNA was analyzed for the presence of polymorphisms at rs2981582 (FGFR2 gene); rs3803662 (TNRC9); rs889312 (MAP3K1); rs3817198 (LSP1 gene); and rs13281615 (8q24). The analyses were performed using PCR amplification and bi-directional sequencing. RESULTS: No differences were identified in the frequency of the polymorphisms that were analyzed among the three groups. However, some associations were identified, such as the occurrence of bilateral breast cancer and homozygosity for the G allele in rs13281615 as well as the correlation between the SNPs rs2981582 and rs13281615 and the number of cancer cases in the family. Regarding the G allele of rs13281615, we observed that the proportion of individuals who were homozygous for this allele increased with the number of generations affected by cancer, regardless of the group where the patients were included. Concerning the rs2981582 we could observe that individuals from group 1 and homozygous CC had fewer cancer (and also fewer breast cancer) cases. Regarding the hormone receptors, we observed an increased frequency in C homozygotes (rs3803662) among estrogen receptor-negative individuals from groups 1 and 3. For rs2981582 (FGFR2), we observed an increased frequency of the T allele in women who were positive for the estrogen and progesterone receptors regardless of the BRCA1/2 mutational status (p = 0.020 and p = 0.014, respectively). CONCLUSION: The results presented here provide interesting data on the modifying effect of polymorphisms on a family history of cancer; this may be a variable to consider in the analysis of tumor diversity, and of the family history observed in families with hereditary breast cancer (even in those harboring the same type of genetic alteration).

8.
Fam Cancer ; 14(2): 333-6, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25564201

RESUMEN

Germline TP53 mutations are associated with Li-Fraumeni syndrome, an autosomal dominant disorder characterized by a predisposition to multiple early-onset cancers including breast cancer (BC), the most prevalent tumor among women. The majority of germline TP53 mutations are clustered within the DNA-binding domain of the gene, disrupting the structure and function of the protein. A specific germline mutation in the tetramerization domain of p53, p.R337H, was reported at a high frequency in Southern and Southeastern Brazil. This mutation appears to result in a more subtle defect in the protein, which becomes functionally deficient only under particular conditions. Recent studies show that the BC phenotype in TP53 mutation carriers is often HER2 positive (63-83%). Considering that the immunophenotype of BC among p.R337H carriers has not been reported, we reviewed immunohistochemistry data of 66 p.R337H carriers in comparison with 12 patients with other non-functional TP53 germline mutation. Although 75% of carriers of these mutations showed significant HER2 overexpression (3+), corroborating previous studies, only 22.7% of p.R337H patients had BC overexpressing HER2. These results reinforce the notion that different germline mutations in TP53 may predispose to BC via different mechanisms.


Asunto(s)
Neoplasias de la Mama/genética , Genes p53 , Mutación de Línea Germinal , Heterocigoto , Adulto , Anciano , Neoplasias de la Mama/etiología , Femenino , Predisposición Genética a la Enfermedad , Humanos , Inmunofenotipificación , Persona de Mediana Edad , Receptor ErbB-2/análisis , Estudios Retrospectivos
9.
PLoS One ; 9(6): e99893, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24936644

RESUMEN

Germline TP53 mutations predispose individuals to multiple cancers and are associated with Li-Fraumeni/Li-Fraumeni-Like Syndromes (LFS/LFL). The founder mutation TP53 p.R337H is detected in 0.3% of the general population in southern Brazil. This mutation is associated with an increased risk of childhood adrenal cortical carcinoma (ACC) but is also common in Brazilian LFS/LFL families. Breast Cancer (BC) is one of the most common cancers diagnosed in TP53 mutation carriers. We have assessed the prevalence of p.R337H in two groups: (1) 59 BC affected women with a familial history (FH) suggestive of hereditary cancer syndrome but no LFS/LFL features; (2) 815 BC affected women unselected for cancer FH, diagnosed with BC at or before age 45 or at age 55 or older. Among group 1 and group 2 patients, 2/59 (3.4%, CI95%: 0.4%-11.7%) and 70/815 (8.6%, CI95%: 6.8%-10.7%), respectively, were p.R337H carriers in the germline. The prevalence of p.R337H was higher in women diagnosed with BC at or before age 45 (12.1%, CI95%: 9.1%-15.8%) than at age 55 or older (5.1%, CI95%: 3.2%-7.7%), p<0.001). The Brazilian founder p.R337H haplotype was detected in all carriers analysed. These results suggest that inheritance of p.R337H may significantly contribute to the high incidence of BC in Brazil, in addition to its recently demonstrated impact on the risk of childhood ACC.


Asunto(s)
Neoplasias de la Mama/genética , Mutación Missense , Proteína p53 Supresora de Tumor/genética , Adulto , Brasil/epidemiología , Neoplasias de la Mama/epidemiología , Femenino , Haplotipos , Humanos , Persona de Mediana Edad , Linaje , Prevalencia
10.
Virchows Arch ; 463(1): 17-22, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23794094

RESUMEN

A few studies have reported phyllodes tumors (PT) of the breast with germline TP53 mutations. Given this potential association and the high frequency of the TP53 p.R337H in southern and southeastern Brazil, the aim of this study was to assess whether p.R337H occurs among women diagnosed with such rare tumors in this region. Benign, borderline, and malignant breast PT were retrieved from eight pathology laboratories, and DNA was extracted from tumor tissue to perform p.R337H analysis. Overall, 128 cases classified as benign, 7 as borderline, and 13 as malignant PT were included in the study. The TP53 p.R337H mutation was identified in tumor cells of eight (5.4 %) cases. Analysis of DNA from non-tumoral tissue was possible in two of these, and both were p.R337H carriers in the germline. In addition, haplotype analysis was done in these two p.R337H carriers showing the presence of the founder haplotype previously reported in Brazilian mutation-positive individuals. Mutation frequency was significantly higher among malignant (3 of 13; 23 %) compared to benign tumors (5 of 128; 3.4 %) (p = 0.004). Mean age at PT diagnosis was not significantly different between mutation carriers and non-carriers. However, when subgroups where analyzed, the difference in age at diagnosis of carriers versus non-carriers within the group of benign tumors reached borderline significance. Our findings reinforce previous evidence that TP53 mutations have an important role in the development of both benign and malignant PT of the breast.


Asunto(s)
Neoplasias de la Mama/genética , Genes p53 , Mutación de Línea Germinal , Tumor Filoide/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Brasil , Femenino , Haplotipos , Humanos , Persona de Mediana Edad
11.
Rev. bras. mastologia ; 23(2): 52-58, abr-jun 2013.
Artículo en Portugués | LILACS-Express | LILACS | ID: lil-783169

RESUMEN

Estima-se que para o câncer de mama, assim como para grande parte dos tumores malignos conhecidos, 5 a 10% sejam de caráter hereditário. A história de câncer em familiares de primeiro grau e a presença de alguns fatores específicos de risco, como câncer de mama bilateral, história familiar de câncer de mama e ovário, e câncer de mama em indivíduo do sexo masculino, são indicadores importantes de risco de câncer de mama hereditário. Os avanços em técnicas de biologia molecular nas últimas décadas resultaram na identificação de genes que, quando alterados, aumentam significativamente o risco de desenvolver câncer de mama, de ovário e outros tumores. Destacam-se os genes supressores tumorais BRCA1 e BRCA2, além de outros genes de predisposição ao câncer de mama identificados, que são igualmente importantes no risco da doença, embora correspondam a uma parcela menor dos casos hereditários. A possibilidade de identificar pacientes e familiares com elevado risco de desenvolvimento de câncer torna possível o emprego de uma abordagem preventiva e de detecção precoce do câncer. Além disso, a identificação de um indivíduo não portador de uma alteração genética em uma família de risco permite a tranquilização dele e elimina gastos/complicações com intervenções preventivas desnecessárias. Famílias de alto risco de desenvolvimento de câncer hereditário apresentam alta prevalência de câncer de mama, além de neoplasia com instalação precoce e com maior agressividade. Dessa forma, o rastreamento nesses casos deve ser diferente, objetivando alcançar a redução da morbidade e mortalidade associadas ao câncer nessa população.


It is estimated that for breast cancer, as well as for the great majority of malignant tumors, 5 to 10% are due to an inherited predisposition. Family history of cancer in first degree relatives and the presence of some specific risk factors, such as bilateral breast cancer, family history of breast and ovarian cancer, and breast cancer in a male person, are important indicators of risk for hereditary breast cancer. Advances in molecular biology in recent decades have resulted in the identification of genes that, when altered, increase significantly the risk of developing breast cancer, ovarian cancer and other tumors, for example, the tumor suppressor genes BRCA1 and BRCA2, as well as other genes predisposing to breast cancer identified, which are equally important in the risk for the disease, although a smaller portion of match cases hereditary. The ability to identify patients and relatives with high risk for developing cancer makes possible the use of a preventive approach and an early detection of cancer. In addition, the identification of a non-carrier individual in a family of high risk allows him to reassures the modification individual and eliminates expenses/complications with unnecessary preventive interventions. The typical profile of a patient with higher risk is high prevalence of breast cancer, earlier ages at cancer diagnosis and the worst prognosis and evolution of the tumor. In this way, follow up for these patients must be different in order to achieve the reduction of morbidity and mortality associated with cancer in this population.

12.
Int J Surg ; 11(6): 496-500, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23579255

RESUMEN

BACKGROUND: The aim of this study was to compare the rates of local postoperative complications among women undergoing modified radical mastectomy with an electric scalpel (ES) or a harmonic scalpel (HS). It is thought that HS use has less postoperative complications, mainly seroma formation. METHODS: This study was a prospective non-randomised clinical trial (NCT01391988) among consecutive patients, performed in parallel. Patients underwent modified radical mastectomy using an HS or ES. We analysed the following operative variables: time, blood loss and seroma volume drainage. Postoperative complications, including seroma, flap necrosis, haematoma and infection were evaluated on the 7th and 14th days. RESULTS: Forty-six patients underwent a MRM with ES and 49 with HS; no differences were observed between the groups. The rate of local complications was 29% in the HS group and 52% in the ES group (p = 0.024). The rates of seroma (16.3% versus 28.3%; p = 0.161), necrosis (4.1% vs. 21.7%; p = 0.013; OR = 0.15), haematoma (2.0% vs. 8.7%; p = 0.195) and infection (2.0% vs. 6.5%; p = 0.351) were lower in the HS group. Adding the findings of all comparative studies using HSs in MRM to the seroma rates in the current study, the seroma rate, expressed as a categorical variable, did not decrease with HS. Seroma was present in 60/219 cases using an HS and in 69/239 cases utilising an ES (p = 0.72). Based on a multivariate analysis, HS decreased the risk of skin necrosis (p = 0.015). CONCLUSIONS: HSs do not decrease the seroma rate. However, this method may be useful in skin sparing mastectomy because it decreases skin flap necrosis.


Asunto(s)
Mastectomía Radical Modificada/instrumentación , Instrumentos Quirúrgicos , Adulto , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Femenino , Humanos , Mastectomía Radical Modificada/métodos , Persona de Mediana Edad , Necrosis , Proyectos Piloto , Complicaciones Posoperatorias/etiología , Estadísticas no Paramétricas , Colgajos Quirúrgicos/patología
13.
PLoS One ; 8(3): e57581, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23469205

RESUMEN

Germline mutations in BRCA1, BRCA2 and TP53 genes have been identified as one of the most important disease-causing issues in young breast cancer patients worldwide. The specific defective biological processes that trigger germline mutation-associated and -negative tumors remain unclear. To delineate an initial portrait of Brazilian early-onset breast cancer, we performed an investigation combining both germline and tumor analysis. Germline screening of the BRCA1, BRCA2, CHEK2 (c.1100delC) and TP53 genes was performed in 54 unrelated patients <35 y; their tumors were investigated with respect to transcriptional and genomic profiles as well as hormonal receptors and HER2 expression/amplification. Germline mutations were detected in 12 out of 54 patients (22%) [7 in BRCA1 (13%), 4 in BRCA2 (7%) and one in TP53 (2%) gene]. A cancer familial history was present in 31.4% of the unrelated patients, from them 43.7% were carriers for germline mutation (37.5% in BRCA1 and in 6.2% in the BRCA2 genes). Fifty percent of the unrelated patients with hormone receptor-negative tumors carried BRCA1 mutations, percentage increasing to 83% in cases with familial history of cancer. Over-representation of DNA damage-, cellular and cell cycle-related processes was detected in the up-regulated genes of BRCA1/2-associated tumors, whereas cell and embryo development-related processes were over-represented in the up-regulated genes of BRCA1/2-negative tumors, suggesting distinct mechanisms driving the tumorigenesis. An initial portrait of the early-onset breast cancer patients in Brazil was generated pointing out that hormone receptor-negative tumors and positive familial history are two major risk factors for detection of a BRCA1 germline mutation. Additionally, the data revealed molecular factors that potentially trigger the tumor development in young patients.


Asunto(s)
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias de la Mama/genética , Carcinoma/genética , Regulación Neoplásica de la Expresión Génica , Mutación de Línea Germinal , Proteína p53 Supresora de Tumor/genética , Adulto , Edad de Inicio , Brasil/epidemiología , Neoplasias de la Mama/epidemiología , Carcinoma/epidemiología , Transformación Celular Neoplásica/genética , Análisis Mutacional de ADN , Femenino , Perfilación de la Expresión Génica , Humanos , Patrón de Herencia , Linaje , Receptor ErbB-2/deficiencia , Receptor ErbB-2/genética
14.
Gland Surg ; 2(2): 102-6, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-25083466

RESUMEN

Over time, surgical techniques have advanced to the point where oncological safety and aesthetic outcomes are the pillars of contemporary breast surgery. Variations of mastectomy came up and started allowing the oncological safety and the possibility of an immediate breast reconstruction. Nowadays the association between plastic surgical techniques and mastectomy with immediate breast reconstruction is one of the best alternatives to treat breast cancer and also improved overall aesthetic outcomes and favors the achievement of contralateral breast symmetry. "Oncoplastic mastectomy" is a feasible term and can be routinely used.

15.
Int J Surg ; 10(9): 500-5, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22858800

RESUMEN

BACKGROUND: Locally advanced breast cancer (LABC) is still common in developing countries. The association between neoadjuvant chemotherapy (NC) and oncoplastic surgery (OS) might provide an oncological treatment with satisfactory aesthetic results. PURPOSE: The goal was to demonstrate if oncoplastic surgical techniques can be utilized to treat LABC which was submitted to neoadjuvant chemotherapy. METHODS: This prospective clinical trial included breast cancer patients, clinical stage III, who underwent established NC regimen. All patients underwent preoperative planning to control the tumor size and to define the surgical technique. A detailed analysis of the pathological specimen was performed. RESULTS: 50 patients were assessed and surgically treated. Tumor size ranged from 3.0 to 14.0 cm (median 6.5 cm). Pathologic response was rated as stable, progressive, partial response, and complete response in 10%, 8%, 80% and 2% of the cases, respectively. Seventeen (34%) patients were submitted to OS. No patient had positive margins. Skin involvement was presented in 36% of pathologic specimen. CONCLUSIONS: Oncoplastic surgical techniques for selected patients decrease the rates of radical surgery despite large tumors. (www.clinicaltrials.gov, NCT00820690).


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/cirugía , Mamoplastia/métodos , Mastectomía Segmentaria/métodos , Adulto , Anciano , Neoplasias de la Mama/patología , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Estudios de Factibilidad , Femenino , Humanos , Persona de Mediana Edad , Terapia Neoadyuvante , Estadificación de Neoplasias , Paclitaxel/administración & dosificación , Estudios Prospectivos , Resultado del Tratamiento
16.
Surg Infect (Larchmt) ; 13(4): 270-5, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22870924

RESUMEN

BACKGROUND: Necrotizing soft tissue infection (NSTI) is characterized by progressive infectious gangrene of the skin and subcutaneous tissue. Its treatment involves intensive care, broad-spectrum antibiotic therapy, and full debridement. METHODS: We present two cases of NSTI of the breast, adding these cases to the 14 described in the literature, reviewing the characteristics and evolution of all cases. CASE REPORT: On the fourth day after mastectomy, a 59-year-old woman with ulcerated breast cancer developed Type I NSTI caused by Pseudomonas aeruginosa, which had a favorable evolution after debridement and broad-spectrum antibiotics. The second patient was a 57-year-old woman submitted to a mastectomy and axillary dissection, who had recurrent seromas. On the 32nd post-operative day, after a seroma puncture, she developed Type II NSTI caused by ß-hemolytic streptococci. She developed sepsis and died on the tenth day after debridement, intensive care, and broad-spectrum antibiotics. The cases are the first description of breast NSTI after mammary seroma aspiration and the first report of this condition caused by P. aeruginosa. CONCLUSION: Necrotizing soft tissue infection is rare in breast tissue. It frequently is of Type II, occurring mainly after procedures in patients with breast cancer. The surgeon's participation in controlling the focus of the infection is of fundamental importance, and just as important are broad-spectrum antibiotic therapy and support measures, such as maintenance of volume, correction of electrolytic disorders, and treatment of sepsis and septic shock. Once the infection has been brought under control, skin grafting or soft tissue flaps can be considered. The mortality rate in breast NSTI is 18.7%, all deaths being in patients with the fulminant Type II form. Surgical oncologists need to be alert to the possibility of this rare condition.


Asunto(s)
Neoplasias de la Mama/cirugía , Fascitis Necrotizante/etiología , Infecciones de los Tejidos Blandos/etiología , Streptococcus pyogenes/aislamiento & purificación , Bacteriemia , Neoplasias de la Mama/microbiología , Fascitis Necrotizante/microbiología , Resultado Fatal , Femenino , Humanos , Mastectomía , Persona de Mediana Edad , Infecciones por Pseudomonas/etiología , Pseudomonas aeruginosa/aislamiento & purificación , Infecciones de los Tejidos Blandos/microbiología
17.
Int J Surg ; 10(5): 265-9, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22446087

RESUMEN

INTRODUCTION: Breast cancer now occurs worldwide and each country has its own approach to breast surgery, which is constantly evolving. A training program was established in Brazil to familiarize breast surgeons with basic oncoplastic techniques and recent developments. MATERIALS AND METHODS: The first 12 breast surgeons participating in the oncoplastic training program were surveyed regarding their experience of Urban's classification of oncoplastic procedures, and whether the training course met their expectations. RESULTS: The most part (11) of the breast surgeons surveyed had been breast specialists for more than five years. Just under one third (27.3%) wished to perform oncoplastic procedures in conjunction with a plastic surgeon. After the course the experience of the first group showed that just over half (seven) of the twelve specialists developed their skills sufficiently to perform Urban procedures at level III, and eleven others could perform until level II procedures. CONCLUSION: Organized oncoplastic training centers can enable breast surgeons to undertake reconstructive breast procedures without the assistance of a plastic surgeon.


Asunto(s)
Neoplasias de la Mama/cirugía , Educación Médica Continua/organización & administración , Mamoplastia/educación , Cirugía Plástica/educación , Adulto , Brasil , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos Educacionales
18.
Rev. bras. mastologia ; 20(2): 66-70, abr.-jun. 2010. tab, graf
Artículo en Portugués | LILACS | ID: lil-605111

RESUMEN

A cirurgia oncopIástica se tornou uma realidade em nosso meio, porém muitos mastologistas necessitam de habilitação nesse contexto. Atualmente, questiona-se quais profissionais podem realizar a oncoplastia e quando poderão realizar esse procedimento, sendo considerada a necessidade de um treinamento mínimo. Objetivo: Avaliar a taxa de realização de cirurgias oncoplásticas e a relação entre o tempo de treinamento do cirurgião em oncoplastia. Métodos: Estudo retrospectivo das 2.129 pacientes submetidas a cirurgia mamária no Serviço de Mastologia de Hospital de Câncer de Barretos, no período de Janeiro de 2006 a Junho de 2008. Todos os procedimentos cirúrgicos foram realizados por cirurgiões oncológicos ou mastologistas. O treinamento em oncoplastia dos profissionais variou de seis meses (cirurgião A) a dez anos (E), com mediana de três anos, sendo três profissionais com três anos de experiencia (B e C); porem, destes, um apresentou treinamento exclusivo em oncoplastia por um ano (D). Procurou-se avaliar o percentual de cirurgias oncoplásticas realizadas no serviço, bem como o risco relativo (RR) do cirurgião como fator de risco para indicação da cirurgia oncoplástica. Resultados: Das cirurgias realizadas, 275 (12,9%) foram catalogadas como cirurgias oncoplásticas. Avaliando os semestres, a taxa de cirurgias oncoplásticas variou de 10,9 a 15%. Em cirurgiões com ênfase exclusiva em cirurgia oncológica, não se observou a realização de cirurgia oncoplástica. Nos cirurgiões com treinamento em oncoplastia, a taxa de realização desse procedimento variou de 2,2 a 33,3%. As frequências das cirurgias oncoplásticas foram, para os cirurgiões A, B, C, D e E, respectivamente, 2,2, 12,2, 12,2, 17,5 e 33,3%. A indicação foi proporcional ao tempo de treinamento (p < 0,001). Considerando o risco de realização do procedimento, tendo como base o cirurgião de menor treinamento (A), observou-se para o cirurgião B um RR 12,3 (IC: 5,2-28,9); para o cirurgião C um RR de 12,5...


Introduction: Oncoplastic surgery became a reality, but many breast specialists need to be able in this context. Objective: To assess the rate of oncoplastic surgeries and the relationship between the breast surgeon training time. Methods: A retrospective study of 2,129 patients undergoing breast surgery at the Department of Mastology of Hospital de Cancer de Barretos (SP), from January, 2006 to June, 2008. All surgical procedures were performed by surgeons or breast cancer specialists. The oncoplastic surgeons training time ranged from six months (surgeon A) to ten years (E), with a median of three years; three professionals had three years of experience (B and C). The surgeon (D) had an exclusive training in oncoplastic by one year. This study evaluated the percentage of oncoplastic surgeries performed in the service, and the relative risk (RR) of the surgeon as a risk factor for oncoplastic surgical indication. Results: Of the surgeries performed, 275 (12.9%) were listed as oncoplastic surgeries. Assessing each six months, the rate of oncoplastic surgeries ranged from 10.9 to 15%. The oncoplastic procedure rate by surgeons with training ranged from 2.2 to 33.3%. The frequencies of oncoplastic procedures by surgeons A, B, C, D and E, respectively are 2.2, 12.2, 12.2, 115 and 33.3%. The statement was proportional to the training time (p < 0.001). Considering the risk of the procedure, based on the surgeon's training under “A”, RR 12.3 was observed for the surgeon B (CI: 5,2 -28,9); RR 12.5 for the surgeon C (C:. 5,3-29,4); RR 18.6 for the surgeon D (CI: 7,6-45,4); and RR of 41.1 for the surgeon E (CI: 119 -94.4) - P < 0.001. Conclusions: The breast surgeon training time influenced the indication of oncoplastic procedures. Oncoplastic training centers should be encouraged.


Asunto(s)
Humanos , Adulto , Capacitación Profesional , Cirugía Plástica/métodos , Neoplasias de la Mama/cirugía , Procedimientos de Cirugía Plástica/educación
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