Thesis (doctoral)--Lund University, 1997. / Added t.p. with thesis statement inserted.

Thesis (doctoral)--Lund University, 1992. / Added t.p. with thesis statement inserted.

Thesis (M.S.)--University of Michigan, 1994.

Thesis (doctoral)--Lund University, 1992. / Added t.p. with thesis statement inserted.

FundaÃÃo Cearense de Apoio ao Desenvolvimento Cientifico e TecnolÃgico / Este estudo teve como objetivo avaliar a qualidade de vida relacionada à saÃde (QVRS), domÃnios afetados das mulheres com cÃncer de mama em tratamento quimioterÃpico. Estudo exploratÃrio de corte transversal, realizado no Centro Regional Integrado de Oncologia e na Santa Casa da MisericÃrdia de Fortaleza, instituiÃÃes de tratamento para o cÃncer de mama. A coleta de dados foi atravÃs de instrumento de dados sociodemogrÃficos e clÃnicas, a avaliaÃÃo da QV com a aplicaÃÃo dos QuestionÃrios EORTC QLQ â C30 (VersÃo 3.0) e EORTC QLQ BR 23, durante o perÃodo de abril a julho de 2012. Foi utilizado o SPSS 20.0 para a anÃlise dos dados e revisado por um estatÃstico. Sendo os resultados apresentados em forma de tabelas e discutidas a luz da literatura existente. Participaram da amostra 145 mulheres com cÃncer de mama em quimioterapia, a mÃdia de idade encontrada foi 52 anos, 56,6% das mulheres tinham companheiro, 24,1% sÃo domÃsticas ou do lar; 55,9% recebia, pelo menos, um salÃrio mÃnimo. A maioria (86 ou 59,3%) procede do interior do estado, 60,7% mulheres apresentaram atà 8 anos de estudo, caracterizando assim, baixa escolaridade na maioria da amostra estudada. Com relaÃÃo aos dados clÃnicos, 43,4% das pacientes estava realizando a quimioterapia neoadjuvante, o restante adjuvante. O esquema mais utilizado foi TAC- Docetaxel + doxorrubicina + ciclofosfamida, em 37,2% das mulheres, com tempo de tratamento predominante menor do que 6 meses, em 66,9% das mulheres. Destaca-se que o escore da QVG resultou (76,14), o que significa que a QVG foi considerada razoÃvel ou satisfatÃria pelas mulheres. A funÃÃo mais afetada foi a emocional e encontrou-se que condiÃÃo fÃsica e o tratamento provocaram alguma dificuldade financeira (MÃdia= 41,83), na maioria das pacientes. Os sintomas com os maiores escores foram insÃnia (37,93), fadiga (36,01), perda de apetite (33,56). Com relaÃÃo ao instrumento QLQ BR-23, o resultado mostra o escore EC= 50,07, significando que muitas mulheres apresentam efeitos colaterais da QT e a satisfaÃÃo sexual prejudicada. Em suma, os resultados do presente estudo mostram o quÃo importante à avaliar a QV e os domÃnios mais afetados da paciente atendida em instituiÃÃes de Fortaleza. à relevante avaliar o bem-estar fÃsico, psicolÃgico, bem como o fÃsico, o social e o ambiental para a qualidade de vida. Com o estudo, pode-se corroborar com as prÃticas clÃnicas pertinentes e as proposiÃÃes de polÃticas de saÃde que satisfaÃam o paciente como um todo.

FundaÃÃo Cearense de Apoio ao Desenvolvimento Cientifico e TecnolÃgico / As inÃmeras mudanÃas no cotidiano de mulheres portadoras de cÃncer de mama, decorrentes de alteraÃÃes cognitivas, podem representar ameaÃa à sua manutenÃÃo biopsicossocial, constituindo assim fator estressante na medida em que solicitam estratÃgias de enfrentamento/coping, cujo objetivo à a reduÃÃo, eliminaÃÃo ou manejo do estresse. A partir disso, o estudo objetivou verificar a ocorrÃncia de estresse e a utilizaÃÃo de estratÃgias de enfrentamento/coping no cotidiano de mulheres diagnosticadas com cÃncer de mama. Estudo transversal, de natureza exploratÃrio-descritiva, realizado no ambulatÃrio de Mastologia da MEAC e no setor de Quimioterapia do CRIO, em Fortaleza-CE. A populaÃÃo foi composta por mulheres que haviam sido recentemente diagnosticadas com cÃncer de mama e que se encontravam em acompanhamento nos referidos locais. A partir de critÃrios estabelecidos e utilizando o processo de amostragem por conveniÃncia, foram incluÃdas 21 mulheres no estudo e que estiveram presentes nos locais de coleta durante os meses de abril a julho de 2010. Utilizou-se como instrumento para obtenÃÃo dos dados um roteiro de entrevista estruturada com dados sociodemogrÃficos e de histÃria da doenÃa, o InventÃrio de Sintomas de Stress para Adultos de Lipp (ISSL) e a Escala Modos de Enfrentar Problemas (EMEP). Os dados foram armazenados e analisados no programa SPSS versÃo 17.0, calculando-se mÃdia e desvio-padrÃo para variÃveis contÃnuas, freqÃÃncia percentual para as categÃricas, alÃm dos testes &#61539;2 e ANOVA na verificaÃÃo de associaÃÃo entre as variÃveis. Em todas as anÃlises, um valor p<0,05 foi considerado significativo. A mÃdia de idade foi de 57,76 anos (DP=13,2), a escolaridade das mulheres apresentou-se com um baixo nÃvel, em mÃdia quatro a seis anos de estudo (DP=1,5). A renda familiar teve uma mÃdia de R$ 966,00 (DP=0,4) e observou-se a mÃdia de dois filhos por mulher. A maioria (85,7%) das mulheres era portadora de carcinoma mamÃrio com indicaÃÃo cirÃrgica como forma de tratamento, havendo maior indicaÃÃo de realizaÃÃo de mastectomia total (42,9%). Do total de mulheres, 42,8% possuÃa indicaÃÃo de realizaÃÃo de quimioterapia neoadjuvante como terapia complementar. O diagnÃstico de estresse esteve presente em 66,7% da amostra, enquanto que em 33,3% das pacientes nÃo foi evidenciado a presenÃa de estresse. Das participantes que se achavam com estresse, as principais fases encontradas foi a de alarme (33,3%) e resistÃncia (33,3%). No grupo com estresse, o principal tipo de enfrentamento utilizado foi a busca pela prÃtica religiosa (42,8%) e no grupo sem estresse observou-se o uso do foco no problema na maioria das mulheres (23,7%), havendo associaÃÃo estatisticamente significativa entre tais variÃveis (teste &#61539;2 ; p=0,007). As mÃdias de idade, renda e nÃmero de filhos entre as mulheres e sua relaÃÃo com o tipo de enfrentamento utilizado, nÃo demonstraram diferenÃas significativas atravÃs do teste F de Snedecor (ANOVA). A pesquisa demonstrou que as mulheres diagnosticadas com cÃncer de mama encontravam-se significativamente estressadas e utilizando como forma de enfrentamento a prÃtica religiosa, havendo a nÃo ocorrÃncia de estresse entre aquelas que estavam procurando enfrentar a doenÃa de forma resolutiva. De qualquer forma as situaÃÃes de estresse provocadas pelo cÃncer de mama requerem uma resposta da mulher, seja uma resposta mais adaptativa ou nÃo, assim, a mulher necessita descobrir quais os mecanismos possÃveis de serem utilizados no processo de enfrentamento. Acredita-se que nesse ponto, a enfermagem tem um importante papel a desempenhar, no sentido de mediar respostas mais adaptativas à situaÃÃo da doenÃa. / The various changes in the daily of women that have breast cancer, arising of cognitive changes, may represents threat to your manteinance biopsychosocial, being a stressful factor because request coping strategies whose aim is the reduction, elimination or management of stress. Thus, the study aimed to verify the occurrence of stress and the use of coping strategies in the daily of women diagnosed of breast cancer. It is a cross-sectional study, descriptive-exploratory, realized in the MEACâs Mastology ambulatory and in the CRIOâs Chemotherapy sector. The population were composed by women that had been diagnosed recent with breast cancer and were in treatment in the locals refered. With criteria established and using the sampling procedure by convenience were included 21 women in the study and that were in the locals of collected during the months from April to July 2010. Used like instrument to obtain the dates a structured interview guide with sociodemographic dates and disease history, the Inventory of Symptoms of Stress to Adults of Lipp (ISSL) and the Ways of Coping Scale (WCS). The dates were stored and analysed in the SPSS program version 17.0, calculating mean and standard deviation to continuous variable, frequency percentage to categorically and the tests &#61539;2 and ANOVA in the verification of association among variables. All the analyses a p value<0.05 was considered statistically significant. The mean of age was 57,76 (DP=13,2), the instruction level was low average four to six years, the family income had a mean of R$966,00 (DP=0,4) and observed the mean of two children by women. Most of women (85,7%) had breast cancer with surgical indication like treatment, having most indication to realize total mastectomy (42,9%). From the total women, 42,8% had indication to realize neoadjuvant chemotherapy like complementary therapy. The stress diagnostic were present in 66,7% of sample while in 33,3% of patients it was not observed. From patients that were with stress, the mean phases were alarm (33,3%) and resistance (33,3%). In the group with stress, the mean type of coping used was the search for religious practice (42,8%) and in the group without stress observed the focus on the problem in the most of women (23,7%), having association statistically significant between these variables (test &#61539;2 ; p=0,007). The means of ages, income and number of children among women and the relation with the type of coping not demonstred association statistically significant with the test F of Snedecor (ANOVA). The research demonstred that the women with breast cancer were significantly stressed and used like way of coping the religious practice, having not occurrence of stress among women that were looking to face the disease of a resolving way. Anyway the stress situations caused by breast cancer request a response of women, be a more adaptive response or not, thus, the woman need to find the possible mechanism to be used in the coping process. It is believed that in this aspect the nursing have an important role to realize in order to mediate the more adapter responses in the diseaseâs situation.

Abstract Radiotherapy is used in the treatment of breast cancer in order to reduce local recurrence rate. However, radiation is known to cause both acute and delayed side-effects on normal tissues. A common late complication of radiotherapy is fibrosis of skin and other organs. Fibrosis has been described as excessive accumulation of extracellular matrix components, especially collagens. Collagens are a group of extracellular matrix proteins that provide connective tissues with tensile strength. Type I and III collagens are the major structural proteins in skin. Alterations in collagen synthesis occur in various pathological conditions, during ageing and in association with diverse medical therapies. Collagens are degraded by matrix metalloproteinase enzymes (MMPs). The activity of MMPs is restrained by their specific tissue inhibitors (TIMPs). Elastic fibres constitute about 2–4% of skin dry weight. Despite their low quantity, elastic fibres are responsible for the resilient and elastic properties of skin. Dermal elastic fibres may be affected by intrinsic ageing, by extrinsic reasons such as photodamage and in several connective tissue diseases. The effect of radiotherapy on human skin type I and III collagen synthesis was investigated in a group of women who had been treated for breast cancer surgically and with radiotherapy. The levels of MMP-9, MMP-2/TIMP-2 complex, TIMP-1 and TIMP-2 in irradiated skin were also analysed. The effect of radiotherapy on elastic fibres was analysed using skin samples. The physio-mechanical properties of radiotherapy-treated skin were studied using ultrasound and elastometer devices, and compared with those of non-treated skin. In addition, skin samples were stained for haematoxylin-eosin, tenascin and mast cells. Factor VIII immunostaining was performed to visualize dermal blood vessels. Wound regeneration in irradiated skin was also studied using suction blister as a model. The synthesis of type I and III collagens was markedly increased as a result of radiotherapy. An increased amount of cross-linked type I collagen was detected in irradiated skin, and collagen turnover was also increased in irradiated skin. No difference in the amount or structure of the elastic fibres could be found between radiotherapy-treated and non-treated skin. A slight increase of skin thickness and stiffness was found in irradiated skin compared to non-treated skin. Increased tenascin expression was found in irradiated skin. The number of dermal blood vessels visualized by FVIII immunostaining was slightly higher in irradiated than in control skin. The amount of mast cells positive for tryptase, Kit receptor and chymase was increased in the upper dermis of irradiated skin. No difference in epidermal regeneration was found between irradiated and non-treated skin. The results of this study suggest that alteration of collagen metabolism contributes to dermal side effects of therapeutic irradiation.

Prognostic indicators, measured at diagnosis, are important in breast cancer. They help clinicians select optimal treatment, provide rational bases for stratification of treatment trials and assist analysis of response to treatment. Univariate statistical survival curves have identified many such indicators. However, they do not explain why some patients, classified as favoured by one or other factor(s), experience early treatment failure, nor why a substantial number with unfavourable signs remain recurrence-free many years later. This study was undertaken to identify independent prognostic factors with the use of multivariate regression. A Cox proportional hazards model of disease-specific survival was based on 1184 primary breast cancer patients referred to the Cancer Control Agency of B.C. between 1975 and 1981 (median follow-up 60 months). Significant univariate associations with overall survival were found for estrogen receptor concentration ([ER]), axillary nodal status (NO, Nl-3, N4+), clinical stage (TNM I, II, III, IV), histologic differentiation and confluent tumor necrosis (minimal, marked). These factors were assessed at primary diagnosis. A subset of 859 patients with complete data on these variables and also histologic type, menopausal status, age, tumor size and treatment was used to fit the multivariate model. Nodal status was the most important independent factor but three others, TNM stage, [ER] and tumor necrosis, were needed to make adequate predictions. A derived Hazard Index defined risk groups with 8-fold variation in survival. Five-year predicted survival ranged from 36% (N4+, loge[ER]=0, marked necrosis) to 96% (NO, loge[ER]=6, no necrosis) with TNM I and 0% to 70% for the same categories in TNM IV. This wide variation occurred across all stages. Study of post-recurrence survival (369 patients) yielded a model with only three independent predictors: [ER], nodal status and tumor necrosis. Survival - overall, recurrence-free and post-recurrent - is predictable by modelling a few factors measureable at diagnosis. Use of ER concentration, rather than the more common ER status (+ or -), greatly strengthens the model. Presence of ER was also shown to be increasingly important as 'protective', attenuating the effect of other factors, as risk of mortality increases. / Medicine, Faculty of / Pathology and Laboratory Medicine, Department of / Graduate

Ph.D., Faculty of Health Sciences, University of the Witwatersrand, 2011 / Oestrogen receptor (ER) mutations have been identified for both ERα and ERβ in previous studies. The effects of the deletion variants due to splice mutations on clinical parameters, prognosis and treatment were examined in 61 breast carcinoma patients and 13 control samples from elective reduction mammoplasty procedures, respectively. RNA extracted from fine needle aspirates (FNAs) of breast tissue was reverse transcribed and using nested PCR and sequence analysis the presence of these variants elucidated. Using Χ2 and Fisher’s exact tests their significance with respect to clinical parameters such as tumour size, nodal involvement, stage, presence or absence of metastases, menstrual status and hormone responsiveness was examined. Kaplan-Meier survival analysis was also determined. The T-47D breast cancer cell line was cloned with two clones being selected for further analysis, namely TCA3 (hormone sensitive) and TCC1 (hormone resistant). These clones were treated for ten passages with oestrogen metabolites, 17-β- oestradiol and oestriol; oestrogen precursors, androstenedione and cholesterol; an anti-oestrogen, 4-hydroxy-tamoxifen; and the aromatase inhibitor aminoglutethimide, respectively. RNA was extracted from the cells initially and after the tenth passage and the ERα and ERβ exon profiles were examined using RT-PCR and sequence analysis. After the tenth passage hormone response tests were performed every 24 hours (up to 96 hours) with cell number being determined using the MTT assay. The results indicate that ERα and ERβ variants do not have any affect with respect to menstrual status and nodal involvement (N). Expression of ERα2 and ERα4 are required by the mouse monoclonal antibody (DAKO ® Clone 1D5) in the immunocytochemical assay used for the recognition of the protein in order to assess ER status and therefore show significance. ERαΔ2 and, contrary to previous investigations, the variant ERαΔ3 were not found to play a role in tumourigenesis. ERαΔ5 was observed to be more prevalent in ERα-positive patients and was usually co-expressed with the complete ERα5 indicating heterodimerization. ERαΔ5 showed no significance with respect to progression of disease or response to hormone treatment. An increase in the ratio of ERαΔ4: wild-type ERα4 indicated an increase in metastatic potential of diseased tissue. ERα4 and ERαΔ4 heterodimers were present in both T-47D clones and after 10 passages the TCA3 clone grown in 10-8M aminoglutethimide indicated a complete loss of ERα4 without altering hormone responsiveness. These results suggest that ERαΔ4 may play a role in progression of disease but not in the acquisition of tamoxifen resistance. ERαΔ6 was observed in 15% of patients but not in the T-47D clones or the control samples. An increase in the expression of ERαΔ6 among patient samples significantly increased their metastatic potential (p=0.018). ERαΔ6 was also observed as significant with respect to stage of disease (p=0.023) indicating the possible relevance of ERαΔ6 in progression of the disease. ERαΔ7 was the most frequently observed variant and did not show any significance with regard to any of the clinical parameters examined. The presence of ERαΔ7 did not show significance with regard to hormone response in vivo but in vitro the presence of this variant, expressed as a heterodimer with the wild-type ERα7, conferred greater sensitivity to tamoxifen in the tamoxifen resistant clone TCC1. Multiple exon deletions of ERα were also observed. The two more significant multiple deletion variants were those involving ERαΔ4, namely, ERαΔ2-ERαΔ6 and ERαΔ4-ERαΔ6. The multiple variant ERαΔ4-ERαΔ6 may be involved in tumour progression. ERβ variants were not examined in as much detail as ERα variants due to insufficient material available for analysis. The two domains, the DNA binding domain and the ligand binding domain, of ERβ were analyzed in a few of the patients and in the T-47D clones. They were not found to be significant with respect to the clinical parameters investigated and the ERβ profiles of the TCA3 and TCC1 clones remained unchanged after 10 passages under varying growth conditions.

by Suk-yee Fung. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1995. / Includes bibliographical references (leaves 95-107). / Abstract --- p.i / Acknowledgement --- p.ii / Table of Contents --- p.iii / List of Tables --- p.v / List of Figures --- p.vii / List of Appendices --- p.viii / Chapter Chapter I - --- Introduction --- p.1 / Introduction --- p.1 / Epidemiology of Breast Cancer --- p.2 / The Aetiology of Breast Cancer --- p.4 / Prognosis --- p.4 / Effects of Breast Cancer --- p.5 / Management of Breast Cancer --- p.6 / Prevention and Early Detection of Breast Cancer --- p.8 / Theoretical Framework --- p.18 / Chapter Chapter II - --- Method --- p.39 / Research Design --- p.39 / Sample --- p.40 / Measures --- p.41 / Procedure --- p.48 / Data Analysis --- p.49 / Chapter Chapter III - --- Results --- p.50 / Chapter 1 --- Sample Characteristics --- p.50 / Chapter 1.1 --- Demographic profile --- p.50 / Chapter 1.2 --- Medical history and health practices --- p.52 / Chapter 1.3 --- Health status and health values --- p.53 / Chapter 1.4 --- Knowledge of breast cancer --- p.54 / Chapter 1.5 --- Attitudes toward breast cancer --- p.55 / Chapter 2 --- Breast Self-Examination Practices --- p.57 / Chapter 3 --- Social Influence on Breast Self-Examination Practices --- p.60 / Chapter 4 --- Health Belief Model Measures --- p.61 / Chapter 5 --- Comparison of Practicers and Non-practicers --- p.62 / Chapter 6 --- Predictors of breast self-examination practices --- p.67 / Chapter 6.1 --- Practicers vs Non-practicers --- p.67 / Chapter 6.2 --- Frequency of breast self-examination --- p.70 / Chapter 6.3 --- Breast self-examination intention --- p.75 / Chapter Chapter IV - --- Discussion & Conclusions --- p.77 / Discussion --- p.77 / Conclusions --- p.93 / References --- p.95 / Appendices --- p.108