Development and validation of a simple questionnaire for the identification of hereditary breast cancer in primary care.

BACKGROUND: Breast cancer is a significant public health problem worldwide and the development of tools to identify individuals at-risk for hereditary breast cancer syndromes, where specific interventions can be proposed to reduce risk, has become increasingly relevant. A previous study in Southern Brazil has shown that a family history suggestive of these syndromes may be prevalent at the primary care level. Development of a simple and sensitive instrument, easily applicable in primary care units, would be particularly helpful in underserved communities in which identification and referral of high-risk individuals is difficult. METHODS: A simple 7-question instrument about family history of breast, ovarian and colorectal cancer, FHS-7, was developed to screen for individuals with an increased risk for hereditary breast cancer syndromes. FHS-7 was applied to 9218 women during routine visits to primary care units in Southern Brazil. Two consecutive samples of 885 women and 910 women who answered positively to at least one question and negatively to all questions were included, respectively. The sensitivity, specificity and positive and negative predictive values were determined. RESULTS: Of the 885 women reporting a positive family history, 211 (23.8%; CI95%: 21.5-26.2) had a pedigree suggestive of a hereditary breast and/or breast and colorectal cancer syndrome. Using as cut point one positive answer, the sensitivity and specificity of the instrument were 87.6% and 56.4%, respectively. Concordance between answers in two different applications was given by a intra-class correlation (ICC) of 0.84 for at least one positive answer. Temporal stability of the instrument was adequate (ICC = 0.65). CONCLUSION: A simple instrument for the identification of the most common hereditary breast cancer syndrome phenotypes, showing good specificity and temporal stability was developed and could be used as a screening tool in primary care to refer at-risk individuals for genetic evaluations.

Cancer genetic counseling in public health care hospitals: the experience of three Brazilian services.

In Brazil, genetic counseling is usually available in university-affiliated medical genetics services located in tertiary centers that provide cancer diagnosis and treatment. The present study aims to describe the structure and characteristics of three cancer genetic services in Brazilian public health care hospitals and discuss alternatives for the identification and prevention of hereditary cancer syndromes in developing countries. The three services presented here are similar in their structure, routine procedures for cancer risk estimation and criteria for the indication of genetic testing. They all demand that genetic counseling be an essential part of the cancer risk evaluation process, before and after cancer predisposition testing. However, when high-risk patients are identified, all services describe difficulties in the access and continuity of genetic and medical services to the patient and his/her at-risk relatives. The services differ in the type of population served, reflecting distinct referral guidelines. This study emphasizes the importance of the creation of new cancer genetic services in other Brazilian regions and the necessity for establishing a collaborative network to facilitate the diagnosis and research of cancer genetic syndromes.

White matter lesions in Fabry disease before and after enzyme replacement therapy: a 2-year follow-up.

PURPOSE: To report the clinical and neuroimaging, central nervous system (CNS) findings of patients with Fabry disease (FD) during 24 months of enzyme replacement therapy (ERT) with agalsidase-alpha. METHOD: Eight patients were included. Six completed 24 months of ERT. Clinical and magnetic resonance imaging (MRI) data were obtained at 0, 12 and 24 months of ERT. White matter lesions (WML) were evaluated as well as their relation to age, symptoms and neurological examination (CNS score). RESULTS: MRI was stable in 3 patients. WML and CNS score worsened in one patient, fluctuated in another, and improved in the sixth patient. In the whole series, there were 15 WML at baseline, and 19 at the 24th month. In two years, 4 lesions disappeared, whereas 8 appeared. CONCLUSION: A widespread pattern of silent WML in FD was seen. In two years, some WML appeared, and some disappeared. If these phenomena were related to the natural history, remains to be demonstrated.

Evolution of uterine cervical cancer mortality from 1979 to 1998 in the State of Rio Grande do Sul, Brazil.

A decrease in uterine cervical cancer (CC) mortality has been observed in developed countries. However, mortality data in Brazil suggest that CC is one of the most frequent causes of cancer death in women; it is the fourth cause of death from cancer in women in Rio Grande Sul State. A time-trend ecological study was performed to analyze CC mortality trends in Rio Grande do Sul from 1979 to 1998. Data were collected from the Mortality Information System, Brazilian Ministry of Health (DATASUS). Standardized mortality ratios were calculated and linear regression was used for time-trend analysis. The impact of cervical cancer death on life expectancy was also estimated for the study population using potential years of life lost (PYLL). Standardized mortality ratios during the study period revealed a positive linear trend of 0.17, and the mean annual mortality rate was 7.58/100,000. Cervical cancer accounted for 21.9 +/- 1.33 PYLL during the period. In conclusion, although CC is a preventable and curable disease, an increase is observed in mortality from this cause in Rio Grande do Sul State, which may suggest failure in screening programs for cervical cancer.

Population prevalence of hereditary breast cancer phenotypes and implementation of a genetic cancer risk assessment program in southern Brazil.

In 2004, a population-based cohort (the Núcleo Mama Porto Alegre - NMPOA Cohort) was started in Porto Alegre, southern Brazil and within that cohort, a hereditary breast cancer study was initiated, aiming to determine the prevalence of hereditary breast cancer phenotypes and evaluate acceptance of a genetic cancer risk assessment (GCRA) program. Women from that cohort who reported a positive family history of cancer were referred to GCRA. Of the 9218 women enrolled, 1286 (13.9%) reported a family history of cancer. Of the 902 women who attended GCRA, 55 (8%) had an estimated lifetime risk of breast cancer ≥ 20% and 214 (23.7%) had pedigrees suggestive of a breast cancer predisposition syndrome; an unexpectedly high number of these fulfilled criteria for Li-Fraumeni-like syndrome (122 families, 66.7%). The overall prevalence of a hereditary breast cancer phenotype was 6.2% (95%CI: 5.67-6.65). These findings identified a problem of significant magnitude in the region and indicate that genetic cancer risk evaluation should be undertaken in a considerable proportion of the women from this community. The large proportion of women who attended GCRA (72.3%) indicates that the program was well-accepted by the community, regardless of the potential cultural, economic and social barriers.

Consistency of self-reported first-degree family history of cancer in a population-based study.

The aim of this study was to assess the prevalence and consistency of self-reported family history of cancer among first-degree relatives (FDR) in a population-based study. Women at primary care units (PCU) were submitted to a questionnaire about cancer family history. Consistency of the report was determined by comparing self-reported history at the PCU to data from subsequent genetic evaluations and/or cancer confirmatory documents. Consistency in relation to degree of education, reported tumor type and reported age at cancer diagnosis in FDR was assessed. In 8,881 women interviewed, the prevalence of cancer in an FDR was 25.14% (CI 95%: 24.14; 25.94). Mean age was 40.29 years and most (70.26%) had < or = 8 years of education. There was a good agreement of self-reported cancer history at the PCU and in subsequent genetic evaluations [Kappa coefficient = 0.76 (P < 0.05)]. Inconsistencies were not related to low literacy (chi (2) = 2.027; P = 0.363). Consistency of the reported information for cancer status, cancer type and age of onset was 92.59%, 85.33% and 92.64%, respectively. The prevalence of cancer history in an FDR was similar to previous reports in other populations. Consistency and reliability of the self-reported information was high, regardless of educational level.

Clinical characterization and risk profile of individuals seeking genetic counseling for hereditary breast cancer in Brazil.

Hereditary breast cancer (HBC) accounts for 5-10% of breast cancer cases and it significantly increases the lifetime risk of cancer. Our objective was to evaluate the sociodemographic variables, family history of cancer, breast cancer (BC) screening practices and the risk profile of cancer affected or asymptomatic at-risk women that undergo genetic counseling for hereditary breast cancer in public Brazilian cancer genetics services. Estimated lifetime risk of BC was calculated for asymptomatic women using the Gail and Claus models. The majority of women showed a moderate lifetime risk of developing BC, with an average risk of 19.7% and 19.9% by the Gail and Claus models, respectively. The average prior probability of carrying a BRCA1/2 gene mutation was 16.7% and overall only 32% fulfilled criteria for a hereditary breast cancer syndrome as assessed by family history. We conclude that a significant number of individuals at high-risk for HBC syndromes may not have access to the benefits of cancer genetic counseling in these centers. Contributing factors may include insufficient training of healthcare professionals, disinformation of cancer patients; difficult access to genetic testing and/or resistance in seeking such services. The identification and understanding of these barriers is essential to develop specific strategies to effectively achieve cancer risk reduction in this and other countries were clinical cancer genetics is not yet fully established.

Population prevalence of hereditary breast cancer phenotypes and implementation of a genetic cancer risk assessment program in southern Brazil

In 2004, a population-based cohort (the Núcleo Mama Porto Alegre - NMPOA Cohort) was started in Porto Alegre, southern Brazil and within that cohort, a hereditary breast cancer study was initiated, aiming to determine the prevalence of hereditary breast cancer phenotypes and evaluate acceptance of a genetic cancer risk assessment (GCRA) program. Women from that cohort who reported a positive family history of cancer were referred to GCRA. Of the 9218 women enrolled, 1286 (13.9 percent) reported a family history of cancer. Of the 902 women who attended GCRA, 55 (8 percent) had an estimated lifetime risk of breast cancer ³ 20 percent and 214 (23.7 percent) had pedigrees suggestive of a breast cancer predisposition syndrome; an unexpectedly high number of these fulfilled criteria for Li-Fraumeni-like syndrome (122 families, 66.7 percent). The overall prevalence of a hereditary breast cancer phenotype was 6.2 percent (95 percentCI: 5.67-6.65). These findings identified a problem of significant magnitude in the region and indicate that genetic cancer risk evaluation should be undertaken in a considerable proportion of the women from this community. The large proportion of women who attended GCRA (72.3 percent) indicates that the program was well-accepted by the community, regardless of the potential cultural, economic and social barriers.

White matter lesions in Fabry disease before and after enzyme replacement therapy: a 2-year follow-up / Lesões da substância branca na doença de Fabry antes e depois da terapia de reposição enzimática: um seguimento de 2 anos

PURPOSE: To report the clinical and neuroimaging, central nervous system (CNS) findings of patients with Fabry disease (FD) during 24 months of enzyme replacement therapy (ERT) with agalsidase-alpha. METHOD: Eight patients were included. Six completed 24 months of ERT. Clinical and magnetic resonance imaging (MRI) data were obtained at 0, 12 and 24 months of ERT. White matter lesions (WML) were evaluated as well as their relation to age, symptoms and neurological examination (CNS score). RESULTS: MRI was stable in 3 patients. WML and CNS score worsened in one patient, fluctuated in another, and improved in the sixth patient. In the whole series, there were 15 WML at baseline, and 19 at the 24th month. In two years, 4 lesions disappeared, whereas 8 appeared. CONCLUSION: A widespread pattern of silent WML in FD was seen. In two years, some WML appeared, and some disappeared. If these phenomena were related to the natural history, remains to be demonstrated.

OBJETIVO: Relatar os achados neurológicos e de imagem do sistema nervoso central (SNC), observados durante 24 meses de tratamento de reposição enzimática (ERT) com agalsidase-alfa, em pacientes com a doença de Fabry (FD). MÉTODO: 8 pacientes foram incluídos; 6 completaram 24 meses de ERT. Os dados foram obtidos aos 0, 12 e 24 meses de ERT. Lesões de substância branca (WML) foram avaliadas assim como sua relação com a idade e o exame neurológico (escore SNC). RESULTADOS: Os achados de ressonância nuclear magnética foram estáveis em 3 pacientes. As WML e o escore SNC pioraram em um caso; flutuaram em um outro caso; e melhoraram no sexto paciente. No todo, havia 15 WML antes da ERT e 19 WML depois de 24 meses de ERT. Em dois anos, 4 lesões desapareceram e 8 novas surgiram. CONCLUSÕES: Viu-se um padrão difuso de WML assintomáticas, na FD. Em dois anos, algumas WML surgiram, enquanto outras desapareceram. Resta demonstrar se esses fenômenos fazem parte da história natural da doença.

Evolution of uterine cervical cancer mortality from 1979 to 1998 in the State of Rio Grande do Sul, Brazil

A mortalidade por câncer de colo de útero tem diminuído em países desenvolvidos. Entretanto, no Brasil, os dados apontam o câncer de colo de útero como uma das mais freqüentes causas de morte por neoplasia em mulheres, estando em quarto lugar no Rio Grande Sul. Este estudo do tipo série-temporal analisa a mortalidade por câncer de colo de útero e a evolução deste fenômeno no Rio Grande do Sul, no período entre 1979 e 1998. Os dados foram extraídos do Sistema de Informação sobre Mortalidade. Coeficientes de mortalidade padronizados foram analisados por meio de regressão linear simples. Estimou-se o impacto da mortalidade por esta causa sobre a duração de vida esperada para esta população utilizando-se o cálculo dos Anos Potenciais de Vida Perdidos (APVP). Observou-se uma tendência linear positiva dos coeficientes de mortalidade padronizados com incremento anual de 0,17, e o coeficiente anual médio dos óbitos no período foi de 7,58/ 100 mil. Esta doença foi responsável por uma média de 21,9±1,33 APVP. Assim, apesar do câncer de colo de útero ser uma doença prevenível e curável, observa-se um aumento de mortalidade por esta causa, sugerindo falhas nos programas de rastreamento desta doença.