Introdução: Anormalidades nos supressores tumorais p14, p16 e p53 são relatadas em diversos tipos de câncer em humanos. Na carcinogênese ovariana, p16 e p53 foram extensivamente estudados, mas p14 foi analisado somente em carcinomas. Objetivo: O estudo visa determinar a expressão imuno-histoquímica de p14, p16 e p53 em tumores ovarianos epiteliais benignos, borderline e malignos. Método: Estudo transversal utilizando imuno-histoquímica em amostras de tumores epiteliais ovarianos emblocados em parafina do Hospital de Clínicas de Porto Alegre. Resultados: p14 foi positivo em 93% dos tumores benignos, 94% dos borderline e 60% dos malignos. A perda de expressão foi estatisticamente associada com carcinomas. p16 foi positivo em 94,6% dos carcinomas, 75% dos tumores borderline e 45,7% dos benignos. p53 foi positivo em 29,7%, 16,7% e 2,9% dos tumores malignos, borderline e benignos, respectivamente. Os subtipos de carcinoma não mostraram diferenças de expressão. Conclusão: Nosso estudo foi o primeiro a descrever a expressão de p14 em tumores benignos e borderline. Ela permanece estável nos benignos e borderline, enquanto os carcinomas exibem uma perda de expressão significativa. Isso pode indicar que anormalidades de p14 acontecem tardiamente na carcinogênese. As taxas de expressão de p16 e p53 foram semelhantes a estudos anteriores. Estudos futuros devem investigar anormalidades genéticas nas sequencias codificadoras de p14 e incluir todos os tipos de tumor epitelial ovariano. / Background: Abnormalities in tumor suppressors p14, p16 and p53 are reported in several human cancers. In ovarian carcinogenesis, p16 and p53 have been extensively studied, but p14 was only analyzed in carcinomas. Aim: This study seeks to determine p14, p16 and p53 immunohistochemical expression in benign, borderline and malignant ovarian epithelial tumors and correlate them with survival and clinical variables. Methods: Cross-sectional study utilizing immunohistochemical staining of p14, p16 and p53 in paraffin-embedded tissue samples from ovarian epithelial tumors obtained from Hospital de Clinicas de Porto Alegre. Results: p14 was positive in 93% of benign, 94% of borderline and 60% of malignant tumors. Loss of expression was statistically associated with carcinomas. p16 was positive in 94.6% of carcinomas, 75% of borderline and 45.7% of benign tumors. p53 was positive in 29.7%, 16.7% and 2.9% of malignant, borderline and benign tumors, respectively. Carcinoma subtypes showed no difference in expression. Conclusions: To our knowledge, this is the first description of p14 expression in benign and borderline tumors. It remains stable in benign and borderline tumors, while carcinomas show a significant absence of staining. This may indicate p14 abnormalities occur later in carcinogenesis. p16 and p53 expression rates show similar results to previous reports. Future studies should investigate genetic abnormalities in p14 coding sequences and include all types of ovarian epithelial tumors.

Magister Scientiae - MSc / OVARIAN cancer research focuses on answering important questions related to the disease, determining whether new approaches are feasible to contribute towards improving current treatments or discovering new ones. This study focused on the transcriptional regulation of genes that have been implicated in ovarian cancer, based on the occurrences of single nucleotide polymorphisms (SNPs) within transcription factor binding sites (TFBSs). Through the application of several in silico tools, databases and custom programs, this research aimed to contribute toward the identification of potentially bio-medically important genes or SNPs for pre-diagnosis and subsequent treatment planning of ovarian cancer. A total of 379 candidate genes that have been experimentally associated with ovarian cancer were analyzed. This led to the identification of 121 SNPs that were found to coincide with putative TFBSs potentially influencing a total of 57 transcription factors that would normally bind to these TFBSs. These SNPs with potential phenotypic effect were then evaluated among several population groups, defined by the International HapMap consortium resulting in the identification of three SNPs present in five or more of the eleven population groups that have been sampled. / South Africa

Thesis on the topic "Search of New biomakers suitable for screening and early diagnostics of cancer" is dedicated to the issue of cancer, a cancer of the breast, prostate, ovarian and after the new findings out as melanom determination of tumor markers and their implications for clinical practice. Their aim is skouted up biomaker suitable for screening and early diagnostics of carcinoma( cancer ) of the breast, ovarian, prostate and malignant melanoma with utilization of various kinds of immunoassay. The theoretical part gives a brief and comprehensive overview of the epidemiology of selected tumors and tumor markers used and their qualities. In the methodological part are given principles applied iminoanalytics methods a list of the statistical methods and a detailed description of the groups of patients. Results section contains tables with results of biomarkers diveded by sort of avalueted tumors. In the discussion are then analyzed facts that follow from the results. It discussed the process and actualy status of searching convenients biomekers and their combinations that can distinguish a population of benign tumors of the population with malignant tumors and markers which are able to distinguish healthy population from the population with malignant tumors of the breast, ovary, prostate and melanoma. This work may serve as a source of knowledge and results to continue in search of such marker that could be used for screening and early diagnosis of cancer and so to improve the prevention of these illneses in the population.

Objetivo: Até 10% dos casos de câncer de mama estão associados com uma síndrome genética de predisposição ao câncer. A identificação de possíveis portadores dessas síndromes e o consequente encaminhamento para aconselhamento genético permitem a adoção de estratégias direcionadas de prevenção e rastreamento capazes de diminuir morbidade e mortalidade. O objetivo do presente estudo foi avaliar a proporção de pacientes com câncer de mama atendidos no Hospital Universitário de Santa Maria (HUSM) que necessitariam ser encaminhados para avaliação genética. Métodos: Pacientes com câncer de mama que iniciaram tratamento oncológico no HUSM durante o ano de 2014 foram considerados elegíveis. Uma entrevista foi conduzida com cada paciente para coleta de dados e exame físico dirigido. O questionário FSH-7 (Family Story Screening 7) e os critérios do NCCN (National Comprehensive Cancer Network) foram utilizados para identificar os pacientes que deveriam ser encaminhados para avaliação genética. Estes pacientes foram então avaliados quanto à indicação de teste genético - de acordo com as recomendações do NCCN para teste genético – e à probabilidade de mutações nos genes BRCA1 e BRCA2 através de modelos de predição de risco (BOADICEA, Penn II, sistema de escore de Manchester e tabelas da Myriad). Resultados: Dentre os 114 participantes do estudo, 65 (57%) preenchiam critérios de encaminhamento para avaliação genética de acordo com as diretrizes do NCCN. O questionário FHS-7 apresentou uma sensibilidade de 90% para identificar estes pacientes, com uma especificidade de 85%. A presença de história pessoal ou familiar de câncer de mama antes dos 50 anos foi o critério mais comum para indicar avaliação genética. Em relação aos testes genéticos, 52 pacientes (45%) deveriam ser testados para mutações nos genes BRCA1 e BRCA2 e 4 pacientes (3,5%) possuíam indicação de teste para mutações em TP53, de acordo com as recomendações do NCCN. Utilizando os modelos de predição de risco, 10,2% a 57,1% dos pacientes apresentavam uma probabilidade ≥ 10% de mutações em BRCA1 ou BRCA2. Conclusão: Este estudo revelou que a maioria dos pacientes com câncer de mama atendidos no HUSM possui indicação de encaminhamento para avaliação genética. A utilização de um questionário simples e rápido poderia identificar 90% destes pacientes. / Objective: Up to 10% of breast cancers are associated with a hereditary cancer syndrome. The identification of possible carriers of these syndromes and the subsequent referral for genetic counselling allow the adoption of tailored screening and prevention strategies capable of reducing morbidity and mortality. The aim of this study is to assess the proportion of patients with breast cancer treated at the University Hospital of Santa Maria (HUSM) that would need to be referred for genetic evaluation. Methods: Breast cancer patients who began cancer treatment at HUSM during the year 2014 were eligible. An interview was conducted with each patient for data collection and targeted physical examination. The FSH-7 (Family Story Screening 7) questionnaire and the NCCN (National Comprehensive Cancer Network) criteria were used to identify patients who should be referred for genetic evaluation. Then these patients were assessed for genetic testing criteria - according to the NCCN recommendations for genetic testing - and the likelihood of BRCA1 and BRCA2 mutations through risk prediction models (BOADICEA, Penn II, Manchester score system and Myriad tables). Results: Among the 114 study participants, 65 (57%) meet referral criteria for genetic evaluation according to the NCCN guidelines. The FHS-7 questionnaire showed a sensitivity of 90% to identify such patients with a specificity of 85%. The presence of personal or family history of breast cancer before age 50 was the most common criteria to indicate genetic evaluation. With respect to genetic testing, 52 patients (45%) should be tested for BRCA1 and BRCA2 mutations and 4 patients (3.5%) had test indication for TP53 mutations in accordance with the recommendations of the NCCN. Using risk prediction models, 10.2% to 57.1% of patients had a BRCA1 or BRCA2 mutations probability ≥ 10%. Conclusion: This study showed that most of the patients with breast cancer treated at HUSM have referral indication for genetic evaluation. The use of a fast and simple questionnaire could identify 90% of these patients.

Introdução: Anormalidades nos supressores tumorais p14, p16 e p53 são relatadas em diversos tipos de câncer em humanos. Na carcinogênese ovariana, p16 e p53 foram extensivamente estudados, mas p14 foi analisado somente em carcinomas. Objetivo: O estudo visa determinar a expressão imuno-histoquímica de p14, p16 e p53 em tumores ovarianos epiteliais benignos, borderline e malignos. Método: Estudo transversal utilizando imuno-histoquímica em amostras de tumores epiteliais ovarianos emblocados em parafina do Hospital de Clínicas de Porto Alegre. Resultados: p14 foi positivo em 93% dos tumores benignos, 94% dos borderline e 60% dos malignos. A perda de expressão foi estatisticamente associada com carcinomas. p16 foi positivo em 94,6% dos carcinomas, 75% dos tumores borderline e 45,7% dos benignos. p53 foi positivo em 29,7%, 16,7% e 2,9% dos tumores malignos, borderline e benignos, respectivamente. Os subtipos de carcinoma não mostraram diferenças de expressão. Conclusão: Nosso estudo foi o primeiro a descrever a expressão de p14 em tumores benignos e borderline. Ela permanece estável nos benignos e borderline, enquanto os carcinomas exibem uma perda de expressão significativa. Isso pode indicar que anormalidades de p14 acontecem tardiamente na carcinogênese. As taxas de expressão de p16 e p53 foram semelhantes a estudos anteriores. Estudos futuros devem investigar anormalidades genéticas nas sequencias codificadoras de p14 e incluir todos os tipos de tumor epitelial ovariano. / Background: Abnormalities in tumor suppressors p14, p16 and p53 are reported in several human cancers. In ovarian carcinogenesis, p16 and p53 have been extensively studied, but p14 was only analyzed in carcinomas. Aim: This study seeks to determine p14, p16 and p53 immunohistochemical expression in benign, borderline and malignant ovarian epithelial tumors and correlate them with survival and clinical variables. Methods: Cross-sectional study utilizing immunohistochemical staining of p14, p16 and p53 in paraffin-embedded tissue samples from ovarian epithelial tumors obtained from Hospital de Clinicas de Porto Alegre. Results: p14 was positive in 93% of benign, 94% of borderline and 60% of malignant tumors. Loss of expression was statistically associated with carcinomas. p16 was positive in 94.6% of carcinomas, 75% of borderline and 45.7% of benign tumors. p53 was positive in 29.7%, 16.7% and 2.9% of malignant, borderline and benign tumors, respectively. Carcinoma subtypes showed no difference in expression. Conclusions: To our knowledge, this is the first description of p14 expression in benign and borderline tumors. It remains stable in benign and borderline tumors, while carcinomas show a significant absence of staining. This may indicate p14 abnormalities occur later in carcinogenesis. p16 and p53 expression rates show similar results to previous reports. Future studies should investigate genetic abnormalities in p14 coding sequences and include all types of ovarian epithelial tumors.

Le cancer de l’ovaire est immunogène et constitue un bon modèle pour étudier l’immunité antitumorale. Nous avons effectué une étude comparative et systématique de la fréquence, du phénotype, de la fonction et de l’impact sur la survie des cellules dendritiques plasmacytoïdes (pDC) et des lymphocytes T régulateurs (Treg) dans le sang, l’ascite et la tumeur. Nous avons observé que les pDC s’accumulent dans les ascites et sont présentes dans certaines tumeurs alors qu’elles sont profondément déplétées dans le sang des patientes. La présence de pDC associées aux tumeurs (TApDC) est un facteur pronostique indépendant associé à une survie sans progression (SSP) plus courte. De plus, les TApDC, mais pas les pDC d’ascite, sont altérées dans leur fonction innée principale de production d’IFN-α en réponse aux TLR ligands in vitro et induisent le développement de lymphocytes T CD4+ producteurs d’IL-10 responsables d’une tolérance immune favorisant la progression tumorale. Les Treg s’accumulent dans les ascites et les tumeurs de l’ovaire mais leur taux dans le sang est comparable aux donneurs sains. Leur accumulation dans les tumeurs et non dans les ascites est un facteur pronostique indépendant associé à une SSP plus longue. Les TATreg ont un phénotype activé et inhibent la production d’IL-10 par les lymphocytes T CD4+ conventionnels associés aux tumeurs. De façon intéressante, les patientes dont les tumeurs augmentent l’infiltration par les Treg Foxp3+ après chimiothérapie néoadjuvante ont une rechute retardée suggérant qu’en plus d’un effet antitumoral direct, la chimiothérapie induit une réponse immune / Ovarian cancer (OC) is an immunogenic disease and represents a good model for studying antitumoral immunity. We performed a systematic comparison between plasmacytoid dendritic cells (pDC) and regulatory T cells (Treg) in blood, ascites, and tumors in term of frequencies, phenotypes, functions, and impact on outcome of OC patients. We found that pDC accumulate in ascites and are present in some tumors whereas they are profoundly depleted in patients’ blood. Their presence within tumors (but not ascites) is deleterious because associated with early relapse of OC patients. Moreover, Tumor associated pDC (TApDC) but not ascite pDC were altered in their innate function, i.e. the production of IFN-α in response to TLR ligands in vitro, and they induce the development of IL-10+ CD4+T cells. All these results suggest that TApDC but not ascite pDC induce immune tolerance allowing cancer progression. Treg accumulate in ascites and tumors but their levels in patients’ blood were not increased. Their accumulation in tumors, but not ascites, was an independent prognostic factor associated with delayed relapse. TATreg showed an activated phenotype and inhibit IL-10 production by CD4+conventional TAT cells. Interestingly, patients whose tumor infiltration by Foxp3+ Treg is increased after neoadjuvant chemotherapy showed delayed relapse suggesting that chemotherapy, in addition to its direct antitumoral effect, induces an immune response

abstract: The phycologist, M. R. Droop, studied vitamin B12 limitation in the flagellate Monochrysis lutheri and concluded that its specific growth rate depended on the concentration of the vitamin within the cell; i.e. the cell quota of the vitamin B12. The Droop model provides a mathematical expression to link growth rate to the intracellular concentration of a limiting nutrient. Although the Droop model has been an important modeling tool in ecology, it has only recently been applied to study cancer biology. Cancer cells live in an ecological setting, interacting and competing with normal and other cancerous cells for nutrients and space, and evolving and adapting to their environment. Here, the Droop equation is used to model three cancers. First, prostate cancer is modeled, where androgen is considered the limiting nutrient since most tumors depend on androgen for proliferation and survival. The model's accuracy for predicting the biomarker for patients on intermittent androgen deprivation therapy is tested by comparing the simulation results to clinical data as well as to an existing simpler model. The results suggest that a simpler model may be more beneficial for a predictive use, although further research is needed in this field prior to implementing mathematical models as a predictive method in a clinical setting. Next, two chronic myeloid leukemia models are compared that consider Imatinib treatment, a drug that inhibits the constitutively active tyrosine kinase BCR-ABL. Both models describe the competition of leukemic and normal cells, however the first model also describes intracellular dynamics by considering BCR-ABL as the limiting nutrient. Using clinical data, the differences in estimated parameters between the models and the capacity for each model to predict drug resistance are analyzed. Last, a simple model is presented that considers ovarian tumor growth and tumor induced angiogenesis, subject to on and off anti-angiogenesis treatment. In this environment, the cell quota represents the intracellular concentration of necessary nutrients provided through blood supply. Mathematical analysis of the model is presented and model simulation results are compared to pre-clinical data. This simple model is able to fit both on- and off-treatment data using the same biologically relevant parameters. / Dissertation/Thesis / Doctoral Dissertation Applied Mathematics 2015

Au cours de ces dernières décennies, des progrès considérables ont été réalisés dans le domaine de l'oncogénétique, activité médicale basée sur les avancées scientifiques de la biologie moléculaire permettant de prédire le risque de survenue d'un cancer. Néanmoins, dans 80% des cas, les analyses génétiques initiales, réalisées auprès de patientes atteintes d'un cancer du sein et/ou de l'ovaire, ne permettent pas d'identifier une mutation délétère sur l'un des deux gènes BRCA. Dans ce cas, le résultat est dit « négatif », alors qu'il existe toujours un facteur génétique résiduel et le risque de développer un autre cancer justifiant la poursuite de la surveillance personnelle et familiale. En collaboration avec des médecins oncogénéticiens de la région Rhône-Alpes, nous avons interrogé les modalités de transmission de l'information dans ce contexte, en évaluant d'une part l'apport d'un document écrit remis aux patientes à l'issue de la consultation et d'autre part la nécessité du cadre de la consultation. Nous avons également tenté de mieux discerner la manière dont les informations orales sont perçues par les patientes. Pour ce faire, nous avons interviewé 88 patientes au cours d'un entretien clinique de recherche et 172 patientes ont répondu à un questionnaire. Les résultats obtenus ont montré : - l'utilité de délivrer un document écrit résumant les informations orales transmises par le médecin ; - le cadre indispensable de la consultation pour délivrer le résultat négatif ; - l'existence d'un message paradoxal, dans la mesure où le résultat « non concluant » est annoncé comme négatif, rendant la compréhension de l'information plus difficile. / Over the last decades, major progresses have been realized in oncogenetics. This medical activity based on scientific advances in molecular genetics predicts cancer risk. However, no deleterious mutation is detected by BRCA1/2 genetic testing for the majority (80 %) of women who suffer from either breast or ovarian cancer. Under this condition, the result is considered as “inconclusive” although there remains an increased risk for developing breast and/or ovarian cancer. The failure to identify a mutation in a diagnostic test does not rule out the existence of a predisposing factor. Surveillance should be pursued for both the patients and their families. In association with genetic counselors of the region Rhône-Alpes, we considered useful to address the question of information delivery in the context of an inconclusive result. We investigated on one hand the benefit from a written document delivered to patients upon the appointment, and on the other hand the usefulness of a disclosure session. We also investigated how patients experienced the oral information given during the counsel session. Therefore, we conducted semi-structured interviews with 88 women while 172 women answered a questionnaire. The observations demonstrate : - a written document, summarizing the oral information delivered by the oncologist, is useful for patients with an inconclusive result; - a disclosure session is absolutely necessary to announce the inconclusive result; - the presence of a “paradox” when the inconclusive result is delivered as a negative one, increasing the degree of comprehension of information more difficult.

A carcinogênese epitelial ovariana tem sido foco de estudos científicos em todo o mundo desenvolvido. A angiogênese tumoral ovariana é um processo multifatorial que resulta em vários produtos pró-angiogênicos. Entre eles, o fator de crescimento vascular endotelial (VEGF) é predominante. Os objetivos deste estudo foram relacionar as dosagens do VEGF dos fluidos peritoneais, do plasma periférico e do infundíbulo pélvico aos níveis de citorredução em pacientes operadas de adenocarcinoma epitelial de ovário (CEO); formular um modelo probabilístico de citorredução e utilizar estas dosagens para estimar a probabilidade do desfecho de citorredução. Além disto, foi criada uma nova variável chamada carga de VEGF. Pelo procedimento step-wise a citorredução foi melhor descrita pela carga de VEGF, mas faltou Normalidade aos resíduos, não sendo possível a adequação de um modelo matemático. Porém, a curva ROC, forneceu uma área sob a curva de 0,84, com sensibilidade de 71,4 % e especificidade variando de 69,5 a 73,9%. O ponto de corte ótimo foi 15,52 log de picograma de carga de VEGF. A odds-ratio (OR) calculada para citorredução ótima descrita pela carga de VEGF foi de 11 (IC= 2,59 ; 46,78). No grupo com estágio avançado (III e IV), a OR foi de 6 (IC= 1,15; 31,22). Apesar do pequeno número de casos, esta nova variável pode vir a ser um auxiliar na determinação de situações onde cirurgia citorredutora deixa de ser a pedra fundamental do tratamento primário do CEO e a indução quimioterápica passe a ter o principal papel na citorredução química antes da cirugia nestes casos. / Epithelial ovarian carcinogenesis has been the focus of scientific studies in developed world. The ovarian tumor angiogenesis is a multifactorial process that results in pro-angiogenic products. Among them, vascular endothelial growth factor (VEGF) is predominant. This study aimed to relate VEGF levels in peritoneal fluids, peripheric plasma and pelvic infundibular plasma to debulking levels in patients operated on for epithelial ovarian carcinoma (EOC), formulate a probabilistic model for debulking and use these measurements to estimate the probability of the outcome of debulking. Moreover, it was created a new variable called burden of VEGF. For step-wise procedure, cytoreduction was better described by of burden VEGF, but missed Normality of residuals, so the adequacy of a mathematical model was not possible. Nevertheless, the ROC curve provided an area under the curve of 0.84, with sensitivity of 71.4 % and especificity varying from 69.5 to 73,9%. The optimal cutoff point was 15.52 log of picograms of VEGF burden. An odds-ratio for optimal cytoreduction described by the VEGF burden was 11 (CI= 2.59; 46.78). In the group with advanced stages (III & IV), the OR was 6 (CI= 1.15; 31.22). Apart from the small number of cases, this new variable might help to determine situations where cytoreductive surgery leaves behind the cornerstone of primary treatment of CEO and the chemotherapic induction comes to have main role in chemical cytoreduction prior to surgery in these cases.

Objetivo: Até 10% dos casos de câncer de mama estão associados com uma síndrome genética de predisposição ao câncer. A identificação de possíveis portadores dessas síndromes e o consequente encaminhamento para aconselhamento genético permitem a adoção de estratégias direcionadas de prevenção e rastreamento capazes de diminuir morbidade e mortalidade. O objetivo do presente estudo foi avaliar a proporção de pacientes com câncer de mama atendidos no Hospital Universitário de Santa Maria (HUSM) que necessitariam ser encaminhados para avaliação genética. Métodos: Pacientes com câncer de mama que iniciaram tratamento oncológico no HUSM durante o ano de 2014 foram considerados elegíveis. Uma entrevista foi conduzida com cada paciente para coleta de dados e exame físico dirigido. O questionário FSH-7 (Family Story Screening 7) e os critérios do NCCN (National Comprehensive Cancer Network) foram utilizados para identificar os pacientes que deveriam ser encaminhados para avaliação genética. Estes pacientes foram então avaliados quanto à indicação de teste genético - de acordo com as recomendações do NCCN para teste genético – e à probabilidade de mutações nos genes BRCA1 e BRCA2 através de modelos de predição de risco (BOADICEA, Penn II, sistema de escore de Manchester e tabelas da Myriad). Resultados: Dentre os 114 participantes do estudo, 65 (57%) preenchiam critérios de encaminhamento para avaliação genética de acordo com as diretrizes do NCCN. O questionário FHS-7 apresentou uma sensibilidade de 90% para identificar estes pacientes, com uma especificidade de 85%. A presença de história pessoal ou familiar de câncer de mama antes dos 50 anos foi o critério mais comum para indicar avaliação genética. Em relação aos testes genéticos, 52 pacientes (45%) deveriam ser testados para mutações nos genes BRCA1 e BRCA2 e 4 pacientes (3,5%) possuíam indicação de teste para mutações em TP53, de acordo com as recomendações do NCCN. Utilizando os modelos de predição de risco, 10,2% a 57,1% dos pacientes apresentavam uma probabilidade ≥ 10% de mutações em BRCA1 ou BRCA2. Conclusão: Este estudo revelou que a maioria dos pacientes com câncer de mama atendidos no HUSM possui indicação de encaminhamento para avaliação genética. A utilização de um questionário simples e rápido poderia identificar 90% destes pacientes. / Objective: Up to 10% of breast cancers are associated with a hereditary cancer syndrome. The identification of possible carriers of these syndromes and the subsequent referral for genetic counselling allow the adoption of tailored screening and prevention strategies capable of reducing morbidity and mortality. The aim of this study is to assess the proportion of patients with breast cancer treated at the University Hospital of Santa Maria (HUSM) that would need to be referred for genetic evaluation. Methods: Breast cancer patients who began cancer treatment at HUSM during the year 2014 were eligible. An interview was conducted with each patient for data collection and targeted physical examination. The FSH-7 (Family Story Screening 7) questionnaire and the NCCN (National Comprehensive Cancer Network) criteria were used to identify patients who should be referred for genetic evaluation. Then these patients were assessed for genetic testing criteria - according to the NCCN recommendations for genetic testing - and the likelihood of BRCA1 and BRCA2 mutations through risk prediction models (BOADICEA, Penn II, Manchester score system and Myriad tables). Results: Among the 114 study participants, 65 (57%) meet referral criteria for genetic evaluation according to the NCCN guidelines. The FHS-7 questionnaire showed a sensitivity of 90% to identify such patients with a specificity of 85%. The presence of personal or family history of breast cancer before age 50 was the most common criteria to indicate genetic evaluation. With respect to genetic testing, 52 patients (45%) should be tested for BRCA1 and BRCA2 mutations and 4 patients (3.5%) had test indication for TP53 mutations in accordance with the recommendations of the NCCN. Using risk prediction models, 10.2% to 57.1% of patients had a BRCA1 or BRCA2 mutations probability ≥ 10%. Conclusion: This study showed that most of the patients with breast cancer treated at HUSM have referral indication for genetic evaluation. The use of a fast and simple questionnaire could identify 90% of these patients.