Assessing breast cancer risk among Iranian women using the gail model

Background: Breast cancer risk assessment is a helpful method for estimating development of breast cancer at the population level. Materials and Methods: In this cross-sectional study, participants consisted of a group of 3,847 volunteers (mean ± SD age: 463 ± 7.59 years) in a convenience sample of women referred to health centers affiliated to Tehran University of Medical Sciences in Tehran, Iran. The risk of breast cancer was estimated by applying the National Cancer Institute's online version of the Gail Risk Assessment Tool. Results: Some 24.9 of women reported having one first-degree female relative with breast cancer, with 8.05 of them having two or more first-degree relatives with breast cancer. The mean five-year risk of breast cancer for all participants was 1.61±0.73, and 9.36 of them had a five-year risk of breast cancer > 1.66. The mean lifetime risk of breast cancer was 11.7±3.91. Conclusions: The Gail model is useful for assessing probability of breast cancer in Iranian women. Based on the their breast cancer risk, women may decide to accept further screening services

Breast cancer risk assessment by Gail Model in women of Baghdad

Objectives: To assess the high incidence of breast cancer (BC) and the effect of its early diagnosis on decreasing morbidity and mortality among Iraqi women.Methods: A descriptive cross-sectional study was conducted and data were collected from 250 women in Baghdad by a questionnaire consisted of demographic and breast cancer risk (BCR) factors questions. Brest cancer risk was calculated using the BCR Assessment Tool (BCRAT) of the National Cancer Institute’s online version (Gail Model).Results: The average age of women was 45.46± 9.2 years. Twenty-six (10.4%) women have first degree relatives who had BC and three of them have more than one. More than half of the women 136 (54.4%) had their menarche at 12–13 years of age. Half of them 126 (50.4%) had their first birth at <30 year of age.The mean five year BCR for all women was 0.95 ± 1.4%, and 19 (7.6%) of them had a five year BCR ≥ 1.7%. Mean lifetime BCR up to age 90 years was 11.13 ± 4.7% and 6 (2.4%) women had high risk. Based on these findings, it can be suggested that employing Gail Model for BCR assessment can help healthcare providers in Iraq to estimate an individual’s probability of developing BC for screening and prevention.Keywords: Breast cancer risk; Gail Model; Ira

Evaluation of the BOADICEA risk assessment model in women with a family history of breast cancer

The ability of the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) model to predict BRCA1 and BRCA2 mutations and breast cancer incidence in women with a family history of breast cancer was evaluated. Observed mutations in 263 screened families were compared to retrospective predictions. Similarly, observed breast cancers in 640 women were compared to retrospective predictions of breast cancer incidence. The ratios of observed to expected number of BRCA1- , BRCA2- and BRCA(1 or 2) mutations were 1.43 (95% CI 1.05–1.90), 0.63 (95% CI 0.34–1.08), and 1.12 (95% CI 0.86–1.44), showing a significant underestimation of BRCA1 mutations. Discrimination between carriers and non-carriers as measured by area under the receiver operating characteristic (ROC) curve was 0.83 (95% CI 0.76–0.88). The ratio of observed to expected number of invasive breast cancers was 1.41 (0.91–2.08). The corresponding area under the ROC curve for prediction of invasive breast cancer at individual level was 0.62 (95% CI 0.52–0.73). In conclusion, the BOADICEA model can predict the total prevalence of BRCA(1 or 2) mutations and the incidence of invasive breast cancers. The mutation probability as generated by BOADICEA can be used clinically as a guideline for screening, and thus decrease the proportion of negative mutation analyses. Likewise, individual breast cancer risks can be used for selecting women whose risk of breast cancer indicates follow-up. Application of local mutation frequencies of BRCA1 and BRCA2 could improve the ability to distinguish between the two genes

Prediction of Breast Cancer Risk in Women over 35 Years Old Living in Villages of Zanjan: A Study Based on Gail Model

Background: Breast cancer is one of the most important malignancies in both developed and developing countries. Objectives: To reduce the burden of this disease, the prediction of individuals at risk and implementation of efficient preventive interventions can be effective. The present study was aimed at investigating five-year and lifetime risks of the breast cancer in a rural community in Zanjan province, Iran. Methods: A total of 435 subjects aged 35 years old were randomly selected using systematic randomization in a rural community in Zanjan. The participation rate was 92.4% (402 women). Data collection instrument was a questionnaire in which all associated variables of Gail model and demographic information were included. The data were analyzed using SPSS software version 18, and mean cancer risks were reported. Results: Family history of breast cancer and history of breast biopsy were found to be positive in 3.5% and 0.3% of participants, respectively. Out of all participants, 84.3% were under 60 years old and 13.2% were illiterate. Five-year and lifetime mean risks were fund to be 0.74% and 7.6%, respectively. About 2% of the participants had a higher cancer risk>1.66%. Conclusion: The findings demonstrated that based on the Gail model, the lifetime risk of the participants will be one out of 13 women. Given the lower estimations of Gail model in the prediction of breast cancer, we suggest general population interventions and high-risk strategies be implemented to decrease problems associated with the breast cancer in the future

DNA Repair Capacity as a Marker of Breast Cancer Susceptibility

Introduction: The wide-ranging prognostic implications of a breast cancer diagnosis highlight the need to better enable women to make informed decisions regarding screening and treatment options. As several cancer susceptibility syndromes have been linked to germline mutations resulting in defective DNA repair, including the predisposition to breast cancer due to BRCA1 and BRCA2 mutations, more subtle defects in DNA repair capacity may contribute to the components driving differential susceptibility within the general population. Hence, understanding the role of DNA repair capacity in breast cancer onset may aid in the development of a more comprehensive risk profile, thereby furthering the effort to target relevant populations for early screening. In the studies undertaken for this dissertation, we employed various methodologies capturing endpoints across different repair pathways detectable in blood to both further elucidate the etiologic basis of breast cancer development and leverage the information into the potential development of a screening biomarker. Methods: For the phenotypic assessment of nucleotide excision repair (NER) capacity, we developed an ELISA-based method to determine benzo(a)pyrene diolepoxide (BPDE)-DNA adduct capacity in lymphoblastoid cell lines. Gene expression levels were assessed with pre-designed Taqman kits in RNA-derived cDNAs from mononuclear cells using a real-time PCR-based platform. Methylation analysis was conducted with in-house designed assays on bisulfite-converted DNA from mononuclear cells using a pyrosequencing platform. Finally, single nucleotide polymorphisms (SNP) genotyping was assessed in DNA derived from white blood cells with pre-designed Taqman SNP genotyping assays using a real-time PCR-based platform. All studies were conducted in sister-sets enrolled in the New York site within the Breast Cancer Family Registry and all statistical analysis was conducted using the R Foundation for Statistical Computing (2011). Results: We did not detect an association between the ELISA-based phenotypic assessment of NER capacity in the lymphoblastoid cells lines of the sister-sets (n=246, 114 sister-sets) and breast cancer risk (OR = 1.0, 95%CI=0.95, 1.04). Furthermore, we did not observe a correlation with previously determined NER capacity in the same population using an immunohistochemical-based method (r= -0.01, p=0.86). In our gene expression study (n=569, 218 sister-sets), women in the lowest tertile of ATM expression had a heightened risk of breast cancer compared to women in the highest tertile of expression, adjusted for age at blood draw and smoking status (OR=2.12, 95%CI=1.09, 4.12). This association was largely restricted to women with an extended family history of breast cancer (pinteraction = 0.06). Additionally, women in the lowest tertile of MSH2 expression also had a heightened risk of breast cancer compared to women in the highest tertile of expression, adjusted for age at blood draw and smoking status (OR=2.75, 95%CI=1.31, 5.79). The association observed between reductions in ATM expression level and breast cancer risk was lost upon incorporating previously determined end-joining capacity of EcoRI-generated sticky end substrates (OR=1.28, 95%CI=0.15, 11.2) and HincII-generated blunt end substrates (OR=1.55, 95%CI=0.15, 15.5) into the model, suggesting that the impact on risk due to reductions in ATM expression maybe partially driven by the reduction in double strand break repair capacity. In our study investigating breast cancer risk due to the impact of epigenetic modulation on DNA repair gene activity (n=569, 218 sister-sets), no association with risk was observed due to differential promoter methylation levels of BRCA1 (OR=1.09, 95%CI=0.98, 1.20), MLH1 (OR=1.19, 95%CI=0.91, 1.55) or MSH2 (OR=0.89, 95%CI=0.48, 1.64). Furthermore, no correlation between BRCA1 and expression (r=-0.05, p=0.39) or MSH2 methylation and expression (r=-0.04, p=0.39) was observed. Finally, our mismatch repair genotyping study (n=714, 313 sister-sets) indicated an association between the variant MutY_rs3219489 (OR=2.23, 95%CI=1.10, 4.52) and breast cancer risk, as well as a borderline association with risk due to the variant MSH2_rs2303428 (OR=1.71, 95%CI=0.99, 2.95). Furthermore, a protective effect was observed due to the variant MLH3_rs175080, restricted to women without an extended family history of breast cancer (pinteraction = 0.03). Conclusion: These studies suggest that the deregulation of targets spanning various DNA repair pathways contribute to the risk of familial breast cancer

The phenomenon of coping for women with primary breast cancer

This study provides insight into the phenomenon of coping, revealing detailed information outlining what the participants coped with and how they managed life, both during and after a diagnosis of primary breast cancer. This experience was reported as a significant life event for all participants, requiring flexible use of different coping styles to adjust to the global disruption in their lives. The interview questions for the study used the existential framework of The Four Dimensions (van Deurzen, 2010; van Deurzen & Arnold-Baker, 2005). This framework guided the extraction of detailed accounts relating to the phenomenon of coping across the physical, personal, social, and spiritual dimensions of lived experience. In addition, participants also shared their experience of time. IPA methodology (Smith et al., 2009) was used to interpret the data, producing findings describing coping across the dimensions of lived existence and time informed by an existential lens, highlighting the use of meaning-focused coping strategies particularly in the social and spiritual dimensions of lived experience. The findings are important because they have significant implications for the psychological support of women with primary breast cancer and point to individual differences in coping repertoires and resources. The researcher recommends how an existential-phenomenological approach could be used with this population. Recommendations for further research include studies that consider coping for women with metastatic breast cancer, studies that specifically explore difficulties in coping with anxiety at the end of breast cancer treatment, studies that explore coping specifically with iatrogenic trauma after breast cancer surgery, and studies that consider coping with long-term burdens of breast cancer, particularly health inequalities for women with fewer socioeconomic advantages

Determinants of adherence to breast cancer screening in primary health care

Trabalho de projeto de mestrado em Bioestatística, apresentada à Universidade de Lisboa, através da Faculdade de Ciências, 2015As doenças oncológicas são um dos principais problemas a nível mundial, sendo a segunda principal causa de morte em Portugal apenas atrás das doenças do aparelho circulatório. O cancro foi a segunda causa de morte na União Europeia em 2006, seguindo as doenças cardiovasculares e tendo sido responsável por cerca de duas em cada dez mortes nas mulheres (23%) e três em cada dez nos homens (29%). Apenas no ano de 2005 estima-se que tenham sido perdidos mais de 17 milhões de anos vida ajustados pelas incapacidades devido ao cancro na região europeia da Organização Mundial de Saúde. Segundo as estimativas da Organização Mundial de Saúde os novos casos de cancro no mundo aumentaram em 2012 e as projeções antecipam um aumento considerável para 19,3 milhões de novos casos por ano até 2025. Devido ao envelhecimento da população espera-se que este número aumente se não forem tomadas medidas. Os cancros da mama, colo do útero e colorretal são uma causa importante de morbilidade e mortalidade na União Europeia. Nas mulheres estes três cancros são responsáveis por cerca de um em cada dois (47%) novos casos de cancro e por uma em cada três (32%) mortes por cancro ao passo que nos homens o carcinoma colo-rectal é responsável por cerca de um em cada oito (13%) novos casos de cancro e uma em cada nove (11%) mortes o que vem aumentar a importância da implementação de programas de rastreio. Em Portugal a situação é semelhantes com o cancro a ser a segunda cause de morte, seguindo as doenças cardiovasculares, sendo responsável por 21,1% dos óbitos. Nas mulheres o cancro da mama é a primeira causa de morte por cancro sendo responsável por 15,9% das mortes. Muitas vezes os médicos não conseguem explicar porque é que uma pessoa desenvolve cancro e outra não. No entanto, a investigação demonstra que determinados fatores de risco aumentam a probabilidade de uma pessoa vir a desenvolver cancro. Atualmente a tendência é de diminuição da mortalidade por cancro da mama e esta passa sobretudo pela prevenção primária. Este tipo de medida é a estratégia mais económica e eficaz no controlo do cancro e estima-se que cerca de um terço de todos os cancros possam ser evitados se forem alterados ou evitados os principais fatores de risco como o tabagismo, o consumo de álcool, exposição à luz solar, radiação ionizante, determinados químicos e outras substâncias, alguns vírus e bactérias, dieta pobre, o escasso consumo de frutas e legumes, falta de atividade física ou excesso de peso. Contudo, ter um fator de risco ou vários não implica que a doença se desenvolva. Muitas mulheres com vários fatores de risco nunca desenvolveram a doença enquanto outras que desenvolveram a doença, aparentemente, não sofriam de qualquer fator de risco. No entanto, também a prevenção secundária pode levar à diminuição da incidência de alguns tipos de cancro mediante deteção e tratamento das suas lesões precursoras. O rastreio consiste na procura ativa de uma doença ou condição precursora de doença em indivíduos presumivelmente saudáveis em risco de desenvolver a doença, de modo a permitir terapêutica precoce. Existem dois tipos de rastreio distintos, o populacional, no qual as pessoas em risco são convidadas a ser submetidas a rastreio, e o oportunista, que ocorre quando se aproveita para sugerir a indivíduos que recorrem aos Cuidados de Saúde Primários por outro motivo. De um modo geral os programas de rastreio organizado são mais eficazes do que os rastreios oportunistas sendo mais económicos, mais fáceis de avaliar e, se necessário, mais fáceis de suspender. Apesar de tudo, na União Europeia só menos de metade dos exames são efetuados no âmbito de programas populacionais que proporcional o enquadramento adequado para a implementação da garantia de qualidade exigida nos termos da recomendação do Conselho Europeu. Rastreio é o processo seletivo para a deteção de formas precoces da doença em indivíduos assintomáticos, visando a melhoria do prognóstico da doença e a redução da mortalidade. O rastreio oncológico pressupõe uma sequência de intervenções em tempo útil e de forma integrada desde a identificação da população alvo até à terapêutica e vigilância após tratamento para detetar o cancro com o objetivo de reduzir a mortalidade e, em alguns casos, a sua incidência. Como o cancro é uma doença potencialmente letal o objetivo principal do rastreio oncológico é a redução da mortalidade por cancro e a avaliação da sua eficácia deve ser feita com base nesta característica. No entanto, nessa avaliação é importante considerar outras consequências importantes como a utilização de recursos de saúde e o impacto na qualidade de vida. A evidência atual é consensual sobre a utilidade de programas de rastreio do cancro em várias áreas, incluindo, no cancro da mama. O rastreio oncológico também acarreta várias limitações. Logo à partida baseiam-se as decisões nos benefícios populacionais em detrimento dos benefícios individuais, realizando testes num grande número de indivíduos assintomáticos, dos quais a grande maioria, não tem a doença em cause e só uma pequena parte usufruirá de benefícios pela deteção precoce do cancro. Outro problema deve-se à acuidade dos testes, mais concretamente, à existência de falsos positivos e falsos negativos. Maioritariamente as pessoas aceitam ser rastreadas pela segurança transmitida por um resultado negativo o que tornaria este o resultado ideal. No entanto, atendendo às características do teste utilizados, perante um resultado negativo, existe sempre possibilidade de se tratar de um falso negativo e a pessoa ter a doença em causa, o que leva a uma falsa sensação de segurança e possível atraso no diagnóstico e tratamento. Para contrariar esta limitação tendem a usar-se testes com maior sensibilidade mas existe um aumento inerente do número de falsos positivos que por sua vez causam ansiedade, rotulagem do individuo e investigação adicional desnecessária com os riscos, custos e limitações associados. Contudo, na Europa, a mortalidade relativa ao cancro da mama reduziu 19% entre 1989 e 2006 devido à implementação das medidas de prevenção estratégica e a uma maior eficácia na terapêutica. Uma medida de prevenção é a mamografia de rastreio e em 2003, o Conselho da União Europeia recomendou a todos os estados membros que as mulheres com idades compreendidas entre os 50 e os 69 anos deveriam efetuar rastreio de dois em dois anos. A mamografia de rastreio provou ser o método mais eficaz. Esta é muito importante pois consegue detetar o cancro da mama mesmo antes da sensação de caroço na apalpação. O presente estudo foi desenvolvido em parceria com a Unidade de Epidemiologia do Instituto de Medicina Preventiva e de Saúde Pública, Faculdade de Medicina da Universidade de Lisboa e o seu principal objetivo é identificar o perfil das mulheres que apresentam um maior atraso relativamente ao rastreio entre mamografias consecutivas. Isto é, as mamografias deveriam ser efetuadas de dois em dois anos, e o objetivo é identificar o perfil das mulheres que mais tempo deixam passar após a marca dos dois anos. Para traçar o perfil da mulher usaram as variáveis disponíveis e tiveram-se em conta os mais comuns fatores de risco de cancro da mama. O objetivo de identificar estas mulheres é perceber se existe algum fator comum explicativo que se possa introduzir no rastreio para que estas cumpram os dois anos. Para modelar os tempos foi usado o modelo de Prentice-Williams-Peterson (PWP), uma extensão do Modelo de Regressão de Cox. Da população inicial (n=41.361) 1.926 mulheres foram incluídas no estudo. Todas as variáveis significativas provaram ter um efeito protetor em relação ao tempo de não rastreio da mulher. Mulheres que usam contraceção hormonal apresentam um decréscimo no tempo de não rastreio de 8,5% quando comparadas com mulheres que não usam contraceção hormonal. Mulhers com índice de massa corporal dentro do intervalo [25;30[ fazem mamografias de rastreio 13,5% com menos atraso quando comparadas com mulheres com índice de massa corporal considerado normal, [18.5;25[. Enquanto que mulheres com índice de massa corporal superior a 30kg/m2 apresentam um tempo de não rastreio inferior em 24,7% quando comparadas com mulheres com índice de massa corporal considerado normal.Cancer is a major cause of suffering and death in the European Union. Every year around 3.2 million Europeans are diagnosed with cancer. In women, every year, there is about 331,000 cases and 90,000 deaths due to breast cancer. A burden that is expected to grow even further due to demographic trends in Europe. But with regular and systematic examinations, using evidence-based screening tests followed by appropriate treatment, it is possible to reduce cancer mortality and improve the quality of life for ones that are suffering from cancer by detecting cancer at earlier stages, when it is more responsive to less aggressive treatment. In December 2003, the European Council unanimously adopted a set of cancer screening fundamental principles as best practice in early detection of cancer. This Council recommended to all member states that they should screen for breast cancer every woman aged between 50 and 69 years old. Although in Portugal, screening started in the 90’s due to a pilot program where it was said that all women between 45 and 69 years old should be screened it was only in 2003 due to the European Council guideline that Portugal adopted screening with a mammogram on a biennial basis for women between 50 and 69 years old. Mammogram screening is the only screening method that has proven to be effective. It can reduce breast cancer mortality by 20 – 30% in woman over 50 years old in high-income countries (when the screening coverage is over 70%) and is has also been associated with less disabling treatments and better quality of life after treatment. The present work was developed in partnership with the Unidade de Epidemiologia do Instituto de Medicina Preventiva e de Saúde Pública, Faculdade de Medicina da Universidade de Lisboa, where the main goal is to identify the profile of women who have a longer screening delay between consecutive mammograms in primary health care units. To study the screening delay it used the Prentice-Williams-Peterson (PWP), an extension to the Cox regression model. From the initial population (n=41,361) 1,926 women were included. All the significant variables prove to have a protective impact on the screening delay. Women who uses hormonal contraception have an 8.5% decrease on the delay when comparing with women who do not use hormonal contraception. Women with BMI in [25 ; 30[ do screening mammograms 13.5% times with less delay when comparing to women with “normal” BMI ([18.5 ; 25[).While women with BMI ≥ 30 do screening mammograms 24.7% with less delay when comparing to women with “normal” BMI ([18.5 ; 25[)

Congregational Health and Wellness Ministry Using Locus of Control to Develop Teaching Methods

Faith communities have a unique opportunity to help congregational members modify health-seeking behaviors in order to reduce modifiable health risk factors. Health researchers have increased their use of health locus of control as a preferred method for studying health promotion and sick-role behaviors. Targeted education and activities designed from the context of the subjects\u27 health locus of control may provide an effective method to influence people to make positive healthy behavior modifications with a higher likelihood of success because locus of control beliefs have been shown to have direct relationships with healthy behavior choices. The health locus of control theory has not been widely used in a faith community structure. This project investigated the potential use of health locus of control to design a faith community program that would reach the congregation in the context of their own current locus of control to help them achieve improved health and wellbeing

Dietary intake and factors affecting vitamin D status of Middle Eastern people in the UK

Vitamin D is derived through the action of solar ultraviolet B radiation on skin and from a limited number of natural food sources, fortified foods and supplements. It is well known that vitamin D plays an active role for calcium and phosphorus absorption but there is also growing evidence of an association between vitamin D insufficiency and various chronic diseases. Middle Eastern populations are known to be at risk of vitamin D deficiency due to a diet low in vitamin D and low sunshine exposure. Obesity is also a risk factor since vitamin D is sequestered in body fat. This thesis examined dietary intake of vitamin D, obesity and other risk factors for deficiency in Middle Eastern people in the UK. A questionnaire based survey was undertaken with 242 Middle Eastern respondents. A total of 85% of the sample was estimated to have a vitamin D intake <5 µg/d. Other risk factors for vitamin D insufficiency included covering skin from sunlight (84% females); low use of supplements (18.5%) and being overweight or obese (49% males and 44% females). Vitamin D intake was lowest in those with primary (1.8 µg/d) and secondary school (2.1 µg/d) education compared to higher education (3.6 µg/d). The survey was followed by dietary assessment of 28 Iraqi adults using repeat 24 hour recalls. The results concurred with the survey: mean intake of vitamin D was (3.2±4.4 µg/d) and 78.5% were overweight or obese. Finally, overweight participants were recruited to observe the effect of fat loss on vitamin D status. Serum 25(OH)D concentrations was measured in Middle Eastern (n=12) and Caucasian adults (n=24). Firstly seasonal changes were observed between October and January (with no weight loss). Then participants were advised on weight reduction to observe the effect of fat loss on serum 25(OH)D. Vitamin D deficiency (<25 nmol/l) was observed in 67% of the Middle Eastern group in October increasing to 92% in January. Of the 36 participants, only 17 lost ≥1kg of fat mass between January and April. No difference was found in serum 25(OH)D between those that lost fat mass and those that did not, and no correlation was found between the amount of fat lost and change in 25(OH)D. In the total sample, there was a negative association between serum 25(OH)D and waist circumference and waist-hip ratio, but no correlation was found between 25(OH)D and fat mass, thus indicating a relationship with visceral fat stores rather than total fat mass.Ministry of the Higher Education and scientific research/Ira