The breast cancer, the second most common cancer in the world, is the most common among women, accounting for 25% of new cases of cancer each year. Statistics indicate an increase in global incidence. Important changes were signed in the last decade in the modalities of adjuvant and neoadjuvant treatments employed in the management of patients with breast cancer. These modifications include the surgical approach, radiotherapy techniques, chemotherapy agents, the routine use of hormonal therapy and the advent of molecular therapies target. All of them have contributed to the positive impact on survival of patients. In the world population, the median survival after five years is 61% to 85% in developed countries, by estimates of the World Health Organization. An increasing prevalence of women survivors are accompanied in late follow-up. However, even after decades, the risk of disease recurrence is maintained. This risk decreases significantly after the first two years of treatment, but it not annulled after more than a decade of recurrence-free survival of breast cancer. The risk factors and interventions that impact on early recurrence are well known, but it this information is not reproducible for late recurrence risk stratification. In this context, the analysis of hormonal receptors (HR), highlighted, estrogen receptors, is used by be related to the incidence of late recurrence of breast cancer. This study aimed to determine the impact of HR on the late tumor recurrence (RTT). The study consisted of data from all patients with RTT, which began monitoring for breast cancer at the University Hospital of Santa Maria between 2000 and 2009. Therefore were analyzed for cases (21) and controls (42) to obtain data on histology and tumor biology, methods of treatment used, and on the characteristics of RTT. The results demonstrated an increased risk RTT associated with advanced stages (moderate or high) of breast cancer (P = 0.01). However the risk of RTT was not associated with the HR profile (P = 0.61) or overexpression of HER-2 oncoprotein (P = 0.48). Also, it was observed that early recurrence risk reduction of breast cancer, obtained with adjuvant therapy, did not extend to the prevention of RTT, which indicates the need for specific routines to prevent RTT. In conclusion, those patients have a significant risk of RTT, regardless of the HR profile. Overall, these patients are not included in most recent studies involving reduction of late risk. / O câncer de mama, segundo tipo mais frequente de câncer no mundo, é o mais comum entre as mulheres, correspondendo por 25% dos casos novos de neoplasias a cada ano. As estatísticas indicam um aumento de sua incidência globalmente. Importantes modificações se firmaram na última década nas modalidades de tratamentos adjuvantes e neoadjuvantes, empregados no manejo das pacientes com câncer de mama. Essas modificações incluem a abordagem cirúrgica, as técnicas de radioterapia, as drogas empregadas na quimioterapia, o uso rotineiro de hormonioterapia e o advento de terapias com alvo molecular. Todas elas têm contribuído para o impacto positivo na sobrevida das pacientes. Na população mundial, a sobrevida média após cinco anos é de 61%, alcançando 85% em países desenvolvidos, conforme estimativas da Organização Mundial de Saúde (OMS). Uma prevalência cada vez maior de mulheres sobreviventes são acompanhadas em seguimento tardio. Contudo, mesmo após décadas, o risco de recorrência de doença se mantem. Esse risco reduz de forma significativa após os primeiros dois anos de tratamento, mas não se anula após mais de uma década de sobrevida livre de recorrência (SLR) do câncer de mama. Os fatores de risco e intervenções com impacto sobre a recorrência precoce são bem conhecidos, mas estas informações não são reprodutíveis para estratificação de risco de recorrência tardia. Neste contexto, a análise de receptores hormonais (RH), em destaque, os receptores de estrógenos (RE), é utilizada por guardar relação com a incidência de recorrência tardia do câncer de mama. Este trabalho buscou determinar o impacto destes RH sobre a recorrência tumoral tardia (RTT). O estudo reuniu os dados de todas as pacientes com RTT, que iniciaram acompanhamento por câncer de mama no Hospital Universitário de Santa Maria (HUSM) entre os anos de 2000 e 2009. Portanto, foram analisados casos (21) e controles (42) para obtenção de dados referentes à histologia e biologia tumoral, às modalidades de tratamentos empregados, e quanto às características da RTT. Os resultados demonstraram um risco maior de RTT relacionada a estágios avançados (moderado ou elevado) de câncer de mama (P=0,01). Contudo o risco de RTT não foi associado ao perfil de RH (P=0,61) ou da superexpressão da oncoproteína HER-2 (P=0,48). Ainda, observou-se que a redução de risco de recorrência precoce de câncer de mama, obtida com tratamento adjuvante, não se estendeu à prevenção da RTT, o que aponta a necessidade de rotinas especificas para prevenir RTT. Conclui-se que as pacientes apresentam significativo risco de RTT, independente do perfil de RH. Globalmente, estas pacientes não estão contempladas na maioria dos recentes estudos envolvendo redução de risco tardio.

Fear of cancer recurrence (FCR) is regarded as one of the most common and distressing issues affecting cancer survivors. Observational studies have identified several modifiable characteristics associated with FCR. However, many of the findings are based on post-hoc analyses and come from studies in which FCR was not identified as a primary outcome. This study sought to overcome these limitations by using a model comprised of cognitive, behavioral, and social characteristics as a framework for examining modifiable characteristics associated with FCR. A sample of 120 patients who had been diagnosed with colorectal cancer and completed cancer treatment in the past 6 to 36 months was recruited during routine outpatient visits or by mail for participation in the study. Medical record reviews were conducted to assess clinical variables, and participants filled out a standard demographic questionnaire as well as self-report measures of characteristics resistant to modification (perceived risk of recurrence, neuroticism, conscientiousness), cognitive modifiable characteristics (self-efficacy, positive beliefs about worry, negative beliefs about worry, misinterpretation of symptoms, intolerance of uncertainty and rumination), behavioral modifiable characteristics (reassurance seeking and health-related reassurance seeking), and social modifiable characteristics (social support and social constraints). As hypothesized, results demonstrated that modifiable characteristics (i.e., self efficacy, positive beliefs about worry, negative beliefs about worry, intolerance of uncertainty, rumination, reassurance seeking, health-related reassurance seeking and social constraints) were associated with FCR (all p’s < .05). Multivariable regression analyses demonstrated that modifiable characteristics accounted for 13% of the variance in FCR beyond that accounted for by non-modifiable characteristics (p < .001), with self-efficacy, rumination and health-related reassurance seeking accounting for unique variance in FCR. This study has identified several modifiable characteristics that should be considered as targets for interventions seeking to reduce FCR among cancer survivors.

In this thesis we present some fundamental results regarding orthogonal polynomials and biorthogonal polynomials, the latter defined as in the article "Cauchy Biorthogonal Polynomials", authored by Bertola, Gekhtman, and Szmigielski. We show that total positivity of the kernel can be weakened and how this implies that interlacement for biorthogonal polynomials holds in general. A counterexample is provided showing that in general there does not exist a four-term recurrence relation such as the one found for the Cauchy kernel. As a direct consequence we show that biorthogonal polynomial sequences cannot be considered orthogonal polynomial sequences by an appropriate choice of orthogonality measure. Furthermore, we motivate a conjecture stating that the more general form of interlacement that exists for orthogonal polynomials also exists for biorthogonal polynomials. We end with suggesting some further work that could be of interest.

>Magister Scientiae - MSc / Odontogenic myxoma (OM) is one of the rare odontogenic tumours that affect the maxilo-facial regions. Skeletal myxomas are more common than soft tissue types in the facial regions. Odontogenic myxomas (OM) are non metastasizing tumours and therefore are considered benign. These lesions are known for their distinctive infiltrative nature which makes complete surgical removal a challenging task.Since the tumour occurs inside the bone and can reach a considerable size with little or no clinical manifestation, the radiologic examination remains the main method to determine the size and the extension of the tumour preoperatively.Aim of the study To assess the different imaging techniques which are currently in use for the diagnosis of the odontogenic myxomas.Materials and methods The images were retrieved from the library of the Department of Diagnostics and Radiology at the Tygerberg Oral Health Centre.Initially each of the imaging modalities was assessed independently to describe the imaging features of odontogenic myxoma on conventional radiograph,Computed Tomography (CT) and Magnetic Resonance Image (MRI). Secondly the imaging features of the three techniques were correlated and contrasted to determine the most valuable imaging modality in the diagnosis of the tumour.Results In this study we found that MRI was superior to other modalities in the ability to show and determine the true extension of the tumours. Therefore, MRI distinguished the tumour tissue from the surrounding structures and soft tissues.Myxomas were found to display characteristic patterns of growth on MRI. These patterns include lobulations and/or budding, nodulation and crevices formation.Moreover T2 weighted images deduced the contents of the tumour by emitting different signal intensities from the various components of the tumours.Additionally, characteristic pattern of contrast uptake differentiated the myxomatous, collagenous parts and presumed the nature of the trabeculae whether it is bony or fibrous.CT also showed the tumour and determined the subtle extension of the tumour into the adjacent structures and bone. Expansion and status of the cortical margin were reliably detected on CT. It also determined the pattern of growth in all tumours whether it is lobulation and/or budding, crevices formation or combination of them. In the present study this feature seemed to be a characteristic finding for all the tumours on CT. Moreover CT was able to compare densities of the tumours to surrounding muscles.Conventional radiography (CR) showed great limitations with regard to diagnostic abilities. Although it displayed the existence of the abnormality in all cases,conventional radiograph failed to detect margins and extension in most of the lesions. Therefore conventional radiograph is not reliable for presurgical assessment of the tumour or in differentiation the tumour from other benign and some malignant tumour. Conclusion In spite of the many limitations and shortcomings, conventional radiography remains the preliminary step in the diagnosis process. However digital imaging techniques provide images of great diagnostic value which is especially helpful in the diagnosis of odontogenic myxoma.

Le cycle sismique s'étend de la centaine à quelques milliers d'années mais les mesures géodésiques et sismologiques s'étendent sur moins d'un siècle. Cette courte échelle de temps d'observation rend difficile la mise en évidence du rôle des paramètres sismotectoniques clefs qui contrôlent la dynamique des failles actives. Pour pallier ce problème d'échelle temporelle, j'ai développé un nouveau modèle expérimental qui reproduit des microséismes le long d'une faille décrochante sur plusieurs centaines de cycles sismiques. Il est constitué de deux plaques de polyuréthane latéralement en contact, reposant sur une couche basale de silicone, simulant le comportement mécanique d'une croûte supérieure élastoplastique couplée avec une croûte inférieure ductile, respectivement. Pour chaque expérience, environ 4000 mesures du champ de vitesses horizontales sont enregistrées. L'analyse des déplacements de surface au cours des phases intersismiques, cosismiques et postsismiques et leur comparaison aux failles sismogéniques montrent que le modèle reproduit correctement les déformations proches de la faille et en champ lointain. J'ai aussi effectué des inversions du champ de vitesses en surface pour évaluer la distribution spatiale du glissement en profondeur le long du plan de faille. Pour comparer les expériences, j'ai développé plusieurs algorithmes permettant d'étudier l'évolution spatio-temporelle des principaux paramètres physiques et les processus de déformation de surface qui caractérisent le cycle sismique. Mes premiers résultats suggèrent que la vitesse de chargement tectonique imposée en champ lointain joue un rôle sur le cycle sismique en influençant la magnitude des séismes, leur temps de récurrence, ainsi que la capacité de la faille à générer des séismes caractéristiques. Une vitesse de chargement lente favorise l'occurrence de forts évènements caractéristiques et une vitesse rapide de nombreux microséismes de magnitude faible à modérée plus distribués le long de la faille. Ma première hypothèse est que ce comportement est contrôlé par le couplage fragile/ductile à la base des plaques de polyuréthane. Pour une vitesse rapide, les forces visqueuses dans la couche basale augmentent de même que ce couplage. Ce processus contraint la base de la faille à glisser à une vitesse proche de sa vitesse long-terme et induit un champ de contrainte plus hétérogène le long de son plan qui favorise les microséismes de magnitude faible à modérée. Pour une vitesse lente, le silicone se comporte comme un fluide newtonien et les forces visqueuses diminuent considérablement, permettant à la faille de rester bloquée sur une plus longue période et d'accumuler plus de déformation élastique. Les contraintes sont ensuite relaxées par de plus larges évènements sismiques. Enfin, j'ai étudié le rôle joué par les variations de contrainte normale le long de la faille sur le glissement cosismique et le comportement long terme du système. Les résultats montrent que la distribution spatiale du glissement cosismique est fortement contrôlée par les variations de résistance de la faille et de l'accumulation des contraintes cisaillantes qui en résultent. Les évènements majeurs se produisent préférentiellement dans les zones d'aspérité de contrainte cisaillante et leur distribution spatiale du glissement suit une tendance similaire à celle de la variation de contrainte normale le long de la faille. L'analyse révèle aussi que l'hétérogénéité de l'état de contrainte initial influence la régularité du cycle sismique et le comportement long terme du modèle. Les résultats de cette étude paramétrique conforte ainsi l'hypothèse selon laquelle la distribution du glissement cosismique le long des ruptures peut fournir des informations pertinentes sur l'état de contrainte initial et pourrait améliorer notre compréhension de l'aléa sismique. Notre approche expérimentale apparaît donc, comme une méthode complémentaire et efficace pour étudier la dynamique des séismes. / Average seismic cycle duration extends from hundred to a few thousands years but available geodetic measurements, including trilateration, GPS, Insar and seismological data extend over less than one century. This short time observation scale renders difficult, then, to constrain the role of key parameters such as fault friction and geometry, crust rheology, stress and strain rate that control the kinematics and mechanics of active faults.To solve this time scale issue, I have developed a new experimental set-up that reproduces scaled micro-earthquakes along a strike-slip fault during several hundreds of seismic cycles. The model is constituted by two polyurethane foam plates laterally in contact, lying on a basal silicone layer, which simulate the mechanical behaviour of an elastoplastic upper crust coupled with a ductile lower crust, respectively. For each experience about 4000 horizontal-velocity field measurements are recorded. The analysis of model-interseismic, coseismic and postseismic surface displacements and their comparison to seismogenic natural faults demonstrate that our analog model reproduces correctly both near and far-field surface strains. I also performed surface-velocity field inversions to assess the spatial distribution of slip and stress at depth along the fault plane. To compare the experiences, we have developed several algorithms that allow studying the spatial and temporal evolution of the main physical parameters and surface deformation processes that characterise the seismic cycle (magnitudes, stress, strain, friction coefficients, interseismic locking depth, recurrence time, ...). My first results suggest that far-field boundary-velocity conditions play a key role on the seismic cycle by influencing earthquake magnitudes and recurrence time, as well as the capability of the fault to generate characteristic earthquakes. We observed that low loading rate favors rare but large strong characteristic events and high loading rate numerous low to moderate magnitude more distributed microquakes. My first hypothesis is that this behaviour may be controlled by the brittle/ductile coupling at the base of foam plates. For a high loading rate, viscous forces in the silicone layer increase as well as coupling at the base of the foam plates. These features force the base of the fault to slip at a velocity close to the far field velocity and induce a more heterogeneous stress field along the fault favoring low to moderate microquakes. For a low loading rate, silicone almost behaves as a newtonian fluid and viscous forces strongly decrease, allowing the fault to remain locked for a longer period and to accumulate more elastic strain. Stresses are then relaxed by larger seismic events.Finally, I investigate experimentally the role played by along fault initial normal stress variations on coseismic slip and long term fault behavior. Results show that coseismic slip patterns are strongly controlled by variations in fault strength and subsequent accumulated shear stress along fault strike. Major microquake events occur preferentially into zone of major shear stress asperities and coseismic slip distributions follow similar trends than initial normal stress variations along the fault. Moreover, our experiment suggest that the heterogeneity of initial stress state along the fault influence the regularity of the seismic cycle and, consequently, long term fault slip behavior. Results of this parametric study comfort, then, the hypothesis that coseismic slip distribution along earthquake ruptures may provide relevant informations on unknown initial stress state and could thus improve our understanding of seismic hazard.Our experimental approach appears then, as an efficient complementary method to investigate earthquake dynamics.

An important characteristic of influenza A is its ability to escape host immunity through antigenic drift. A novel influenza A strain that causes a pandemic confers full immunity to infected individuals, yet because of antigenic drift, these individuals have decreased immunity to drifted strains. We compute the required decrease in immunity so that a recurrence is possible. Models for influenza A must make assumptions on the host contact structure on which the disease spreads. By computing the reproduction number, we show that the classical random mixing assumption predicts an unrealistically large decrease of immunity before a recurrence is possible. We improve over the classical random mixing assumption by incorporating a contact network structure. A complication of contact networks is correlations induced by the initial pandemic. Thus, we provide a novel analytic derivation of such correlations and show that contact networks may require a dramatically smaller drop in immunity before recurrence. Hence, the key new insight is that on contact networks the establishment of a new strain is possible for much higher immunity levels of previously infected individuals than predicted by the commonly used random mixing assumption. This suggests that stable contacts like classmates, coworkers and family members are a crucial path for the spread of influenza in human population. / Graduate

Fear of cancer recurrence (FCR) is defined as “fear, worry, or concern relating to the possibility that cancer will come back or progress (Lebel et al., 2016, p. 3266). FCR is the most frequently reported concern identified among cancer survivors (Baker, Denniston, Smith, & West, 2005; Lebel, Rosberger, Edgar, & Devins, 2007). Although approximately 50% of cancer survivors experience moderate-to-high levels of FCR (Simard et al., 2013), few psychosocial interventions exist that directly target this construct. The overarching study objectives were: (a) to adapt a manualized, 6-week, cognitive-existential group therapy intervention for FCR to an individual format; (b) to pilot-test the feasibility, acceptability, and satisfaction of this individual intervention on n=3 participants; and (c) to further pilot-test the efficacy of the individual intervention on n=25 participants, via a randomized controlled trial (RCT). In study 1, n=3 cancer survivors (1 male, 2 females) completed the one-on-one therapy intervention for the psychological treatment of FCR. Sessions were 60-90 minutes long, and included cognitive restructuring exercises, behavioural experiments, relaxation techniques, existential processing of the here-and-now, and finding meaning in life post-diagnosis. Participants completed questionnaire packages throughout the intervention and an exit interview to determine their overall feedback on the intervention. Quantitative analyses revealed downwards trends in fear of cancer recurrence and cancer-specific distress across participants. Qualitative analyses of the exit interviews revealed that all participants found the intervention useful, and that the sessions had favourable pacing and length. In study 2, the FCR intervention was further pilot-tested via an RCT. Twenty-five female cancer survivors were randomized to an experimental group or a wait-list control group. Sessions included cognitive restructuring techniques, behavioural experiments, confronting existential distress, and relaxation exercises. Nineteen women (n=9 intervention, n=10 control) completed the 6-week therapy intervention, and completed questionnaire packages at pre-, post- and 3-month follow-up. Between-within ANOVAs revealed significant interactions in the primary outcome measure of FCR, and secondary outcome measures of cancer-specific distress and uncertainty in illness for participants in the experimental group. Repeated measures ANOVAs revealed reductions in FCR, cancer-specific distress, uncertainty in illness, reassurance-seeking, cognitive avoidance, and intolerance of uncertainty, and revealed improvements in positive reinterpretation and growth, use of emotional support and mental health (improved quality of life) for participants in the experimental group, as compared to the wait-list control group. The variables that changed either maintained or improved at follow-up. Results from this study demonstrate promising results in addressing FCR in cancer survivors via a cognitive-existential intervention. Future research should continue investigating the specific therapeutic ingredients that are most effective for the psychological treatment of FCR.

Parenting is a primary role for many young breast cancer survivors and the combined effect of parenting while coping with this disease can be problematic for many of them. Despite this, little is known about the impact of parenting on the well-being of young breast cancer survivors. This thesis, comprising two studies in article format, explores this question. In the first study, we identified elements of well-being that are salient for all young women with breast cancer, and which also captured some of the unique challenges associated with parenting as a survivor. Using factor analysis techniques, we determined how these elements interrelated in separate groups of young survivors with children and without, and identified differences between the two groups based on the patterns observed. We found that the interrelationship among elements of well-being varied between these two groups: psychological distress (representing mental health and perceived stress), illness intrusiveness, and fear of cancer recurrence were found to co-occur more frequently in mothers than in young survivors without children, thus compromising their well-being. Our second study had two objectives. The first part examined differences in perceived stress, illness intrusiveness, and fear of cancer recurrence between young breast cancer survivors with and without children in two separate timeframes (0-5 and 5-15 years since diagnosis). The second part identified predictors for these elements of well-being in young mothers exclusively. Compared to survivors without children, young mothers reported higher levels of fear of cancer recurrence and illness intrusiveness in intimate life domains during both timeframes, suggesting that disruptions in these areas persist over time. Part two revealed that mothers with adolescent children and high levels of parenting stress were most likely to report perceived stress and illness intrusiveness. A mother’s age and the time since her diagnosis predicted fear of cancer recurrence and illness intrusiveness, respectively. Results from this thesis indicate that young mothers with breast cancer need screening and interventions to manage psychological distress, fear of cancer recurrence, and illness intrusiveness, particularly in intimate life domains. This thesis also identifies the most vulnerable groups of mothers and has important implications for future research.

Orientador: Cesar Cabello dos Santos / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-04T02:24:06Z (GMT). No. of bitstreams: 1 Feijo_LuizFernandoAndrade_M.pdf: 3050164 bytes, checksum: 672560c57474869fce1041591b88e14b (MD5) Previous issue date: 2005 / Resumo: Objetivo: Avaliar as taxas de recidiva local após o tratamento cirúrgico conservador de câncer de mama em mulheres submetidas à radioterapia complementar sem reforço. Pacientes e métodos: Foi realizado um estudo de coorte reconstituído com 128 pacientes portadoras de câncer de mama estádios I e 11,que foram tratadas com cirurgia conservadora e radioterapia sem reforço, no período de janeiro de 1989 a dezembrode 1996, no Setor de Mastologia do Centro de Atenção Integral à Saúde da Mulher (CAISM) da Universidade Estadualde Campinas (UNICAMP).A cirurgia da mama foi a quadrantectomiacom axilectomia,seguida de radioterapiacom 25 frações diárias de 2Gy ou 1,8Gy, cinco dias por semana. As pacientes receberam dose total de 50 ou 45Gy, respectivamente. Foi considerada recidiva local a presença de carcinoma (invasivo ou ductal in situ), confirmado através de exame anátomo-patológico, na mama tratada em qualquer momento do período de seguimento. As pacientes foram estudadas segundo os seguintes critérios: faixa etária, tamanho do tumor, presença de gânglios linfáticos axilares comprometidos e intervalo entre a data da cirurgia e a data do início da radioterapia. A análise estatística foi realizada utilizando Curvas de Kaplan Meyer para apresentar as taxas de recidivas locais e os testes de Log Rank, Wilcoxon e razão de risco para avaliar a relação entre os valores de recidiva local e as variáveis: faixa etária, tamanho do tumor, gânglios linfáticos comprometidos e intervalo entre a data da cirurgia e a data do início da radioterapia. Foi também realizada uma análise multivariada para avalia a independênciae a associação entre as variáveis estudadas e a recidiva local. Resultados: A taxa de recidiva local na população geral foi de 28% em 12 anos de seguimento. As pacientes com idade abaixo de 35 anos apresentaram risco de recidiva local três vezes maior do que as com idade acima de 35. Esses valores encontraram-seno limite da significância (p=0,05); (HR=3,0; 95%IC=1,0 - 9,0).Os tumores com tamanho maior de dois centímetros apresentaram risco de recidiva local três vezes maior do que os tumores menores. Esses valores também se encontraram no limite da significância (p=0,05); (HR=3,0; 95%IC=1,0 - 9,0).As taxas de recidivas locais não se associaram ao estado dos gânglios linfáticos axilares (p=0,09); (HR=1,9; 95%IC=0,8-4,9),assim como não se associaram ao intervalo entre a data da cirurgia e a data do início da radioterapia (p=0,5); (HR=0,9; 95%IC=0,3-2,8).Segundo a análise multivariada,a idade abaixo de 35 anos foi a que apresentou a maior associação às recidivas locais (HR=5,0; 95%IC=1,6-18), seguida dos tumores maiores de dois centímetros (HR= 4,0 - IC= 1,2 - 14). Conclusão:As pacientes tratadas de forma conservadora por câncer de mama e submetidas à radioterapia complementar com dose de 45 ou 50GY sem reforço apresentaram 28% de recidivas locais após 12 anos. Essa taxa foi mais elevada do que as observadasem outros estudos que utilizaram radioterapia com reforço.As com idade abaixo de 35 anos, bem como as portadoras de tumores maiores de dois centímetros, associaram-se a um maior risco de recidivas locais. Esses dados sugerem que essa forma de radioterapia seja insuficiente para o tratamento local dessas mulheres, principalmente nos casos de pacientes com idade inferior a 35 anos ou com tumores maiores de dois centímetros / Abstract: Purpose: To evaluate local recurrence rates after breast-conserving surgery for breast cancer treatment in women undergoing adjuvant radiotherapy without a boost. Patients and methods: A retrospective cohort study was conducted on 128 patients diagnosed with stages I and 11breast cancer, who were treated with conservative surgery and radiotherapy without a boost dose in the Division of Senology at the Women's Integral Health Care Center (CAISM) of the Campinas State University (Unicamp) from January 1989 to December 1996. The type of breast surgery was quadrantectomy with axillary Iymph node dissection, followed by radiotherapy delivered in 25 daily fractions of 2 Gy or 1.8 Gy, tive days a week. The patients received a total radiation dose of 50 or 45 Gy, respectively. Local recurrence was defined as the presence of carcinoma (invasive or ductal in situ) in the treated breast, confirmed by histopathologic exam, at any given time during the follow-up period. The patients were studied according to the following criteria: age range, tumor size, presence of involved axillary Iymph nodes and the interval between the date of surgery and the date when radiotherapy began. Statistical analysis was performed using Kaplan Meyer curves to show local recurrence rates. The log-rank test, the Wilcoxon test and risk ratio were used to evaluate the relationship between local recurrence values and variables, e.g. age range, tumor size, Iymph node involvement and the interval between date of surgery and date when radiotherapy began. Multivariate analysis was also performed to evaluate independence and the association between the variables studied and local recurrence. Results: The local recurrence rate was 28% in the general population at twelve years of follow-up. Patients under 35 years had three times more risk of developing local recurrence than those older than 35 years. These values were found within the significance limit (p=0.05); (HR=3.0; 95%CI=1.0 - 9.0). Women with tumors larger than 2 centimeters had three times more risk of developing local recurrence than those with smaller tumors. These values were also found within the significance limit (p=0.05);(HR=3.0; 95%CI=1.0 - 9.0). Local recurrence rates were neither associated with axillary Iymph node status (p=0.09); (HR=1.9; 95%CI=0.8-4.9), nor with the interval between the date of surgery and the date when radiotherapy began (p=0.5); (HR=0.9; 95%CI=0.3- 2.8). According to multivariate analysis, age under 35 years was most strongly associated with local recurrences (HR=5.0; 95%CI=1.6-18), followed by tumors larger than 2 centimeters (HR= 4.0; 95%CI= 1.2 - 14). Conclusion: Patients treated conservatively for breast cancer and undergoing adjuvant radiotherapy in doses of 45 or 50 Gy without a boost had local recurrence rates of 28% afier 12 years. This rate was higher than those observed in other studies using radiotherapy with a boost. Age under 35 years and tumors larger than 2 centimeters were associated with a higher risk of local recurrences. Our data suggest that this type of radiotherapy was insufficient for the local treatment of these women, especially patients under 35 years of age or those with tumors larger than two centimete / Mestrado / Tocoginecologia / Tocoginecologia

Orientador: Carmen Silvia Bertuzzo / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-28T01:52:48Z (GMT). No. of bitstreams: 1 Vencatto_RobyWill_M.pdf: 2327467 bytes, checksum: 906caea2ae7f9182396080360689d4a1 (MD5) Previous issue date: 2015 / Resumo: O câncer de mama é classificado mundialmente, como o segundo tipo de câncer mais frequente e comum entre as mulheres e tem natureza multifatorial. O tratamento sistêmico do câncer é denominado quimioterapia antineoplásica, e o seu efeito terapêutico depende da concentração plasmática e tempo de exposição à droga. A resposta aos medicamentos possui variação entre os pacientes, podendo decorrer de fatores como: outras patologias, farmacocinética e farmacodinâmica diferenciadas, fatores ambientais e genéticos, sendo este último, estudado na farmacogenética e farmacogenômica, onde se verifica a resposta ao tratamento pela variação herdada de cada indivíduo. Em determinadas populações, polimorfismos podem levar a respostas diferenciadas de um medicamento por induzir peculiaridades na genética, farmacocinética ou farmacodinâmica. Em muitos medicamentos em uso, os transportadores de drogas são importantes na questão de absorção, acumulação no tecido e eliminação do organismo. O gene 'ABCB1' codifica a glicoproteína-P que é um transportador de membrana, responsável pelo efluxo celular de uma variedade de drogas, xenobióticos, metabólitos celulares e agentes anticancerígenos, estruturalmente independentes. Assim, o objetivo do presente estudo foi verificar se os polimorfismos C1236T e G2677T/A do gene 'ABCB1', possuem associação com a resposta ao tratamento quimioterápico. Foi realizado estudo com 146 pacientes do sexo feminino, que usaram os quimioterápicos doxorrubicina e ciclofosfamida de forma adjuvante, independente se fizeram quimioterapia neoadjuvante. A presença de recidiva foi utilizada como parâmetro de avaliação do tratamento. A genotipagem dos polimorfismos foi feita por reação da polimerase em cadeia alelo específica. As análises de sobrevivência livre da doença e global foram realizadas pelo software SPSS (Statistical Package for the Social Sciences) vs20.0 e as demais avaliações no SAS (StatisticalAnalysis Software) vs 9.3. ... Observação: O resumo, na íntegra, poderá ser visualizado no texto completo da tese digital / Abstract: Breast cancer is classified worldwide as the second most frequent and common cancer among women and has a multifactorial nature. The systemic treatment of the cancer is called chemotherapy, and its therapeutic effect depends on the plasma concentration and length of exposure to the drug. The drug response varies among patients and may be the result of many things, such as: other diseases, different pharmacokinetics and pharmacodynamics, environmental and genetic factors. Genetic factors are studied in pharmacogenetics and pharmacogenomics, which verify the response to the treatment through the inherited variation of each individual. In some populations, polymorphisms can lead to different responses to a drug by inducing peculiarities on the pharmacokinetics or pharmacodynamics. In many drugs in use, the drug carriers are important in terms of absorption, accumulation in tissue and elimination from the body. The 'ABCB1' gene, which encodes the P-glycoprotein that is a membrane transporter, responsible for the cellular efflux of a variety of drugs, xenobiotics, cellular metabolites and anticancer agents, structurally independent. Thus, the objective of this study was to determine whether the C1236T and G2677T/A of the 'ABCB1' genes could be associated with the response to chemotherapy. The study featured 146 female patients who used doxorubicin and cyclophosphamide adjuvantly, independent of the neoadjuvant chemotherapy. The relapse was used as a parameter of association to the treatment. Genotyping of polymorphisms was performed by polymerase in specific allele chain reaction. The free and global survival analysis, was performed by the SPSS (Statistical Package for Social Sciences) software vs 20.0. Other statistical tests were performed by SAS (Statistical Analysis Software) vs 9.3.... Note: The complete abstract is available with the full electronic digital thesis or dissertation / Mestrado / Ciencias Biomedicas / Mestre em Ciências Médicas