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Introdução: O aumento de peso corporal e o IMC entre 25 e 29,9 kg/m2 (risco de obesidade) ou 30 kg/m2 (obesidade), no momento do diagnóstico do câncer de mama, são fatores de risco, reconhecidos, para a recidiva da doença e redução do tempo de vida das mulheres. Objetivo: verificar os efeitos da quimioterapia adjuvante sobre o peso e índice de massa corporal de mulheres com câncer de mama. Métodos: o estudo foi descritivo, exploratório, com coleta de dados, a partir de prontuários e contato telefônico, de uma amostra de conveniência de 66 mulheres, com câncer de mama, e submetidas à quimioterapia adjuvante, no período de 2000 a 2008. As variáveis de estudo foram peso e índice de massa corporal, protocolo quimioterápico, número de ciclos de quimioterapia, fase do climatério (pré e pós-menopausa), ingestão alimentar e prática de atividade física. A análise estatística foi realizada por meio dos testes qui-quadrado, t-Student e ANOVA. Foi adotado nível de significância de 0,05 e intervalo de confiança de 95%. Resultados: as mulheres tinham, em média, 49 anos de idade (26 - 75 anos), sendo que a alteração de peso corporal foi associada, significativamente (p < 0,05), com número de ciclos de quimioterapia e alteração da prática de atividade física, enquanto o protocolo quimioterápico, a fase do climatério e a ingestão alimentar não alteraram, significativamente, o peso corporal; não houve diferença, estatisticamente significante, entre IMC, no início da quimioterapia, e as demais variáveis do estudo. Conclusões: o maior o número de ciclos e a prática de atividade física foram estatisticamente significantes, com alteração do peso corporal. / Introduction: The increase of body weight and the BMI between 25 to 29,9 kg/m2 (overweight) or 30 kg/m2 (obese), at the moment of breast cancer diagnosis, are factors of risk, acknowledged, for the recurrence of disease and reduction of survival. Objective: to access the effects of adjuvant chemotherapy on body weight and body mass index in women with breast cancer diagnosis. Methods: the study was descriptive, exploratory, with data collected from medical record and phone contacts with women diagnosed breast cancer, which had undergone adjuvant chemotherapy between 2000 and 2008. The study variables were body weight and body mass index, chemotherapy regimens, number of cycles of chemotherapy, menopausal status (pre and pos menopause), dietary intake and physical activity. The statistical analysis was done by qui-square, t-Student and ANOVA. The significance level adopted was 0,05 and the confidence interval was 95%. Results: 66 women were analyzed, averaging 49 years old (26 to 75 years old), and the body weight difference was associated, significantly (p < 0,05), to the number of cycles of chemotherapy and changes in the physical activity practice, while the chemotherapy regimens, menopausal status and the dietary intake didnt change the body weight significantly; there was no statistically significant difference between BMI, in the beginning of chemotherapy and others variables.Conclusions: number of cycles and physical activities practice were statistically significant, with changes in body weight.

Chemotherapy and adjuvant endocrine treatment for breast cancer has been associated with varying degrees of cognitive dysfunction, with 15-50% of women reported to experience subtle cognitive decline. While these treatments may have direct adverse consequences on neurological functioning, cancer diagnosis and treatment is also associated with many health and psychosocial factors that may decrease performance on neuropsychological tests. However, despite a growing body of literature on affected cognitive domains and observable neurological changes after chemotherapy, there has not been a thorough investigation into potentially important psychosocial and physical health mechanisms that may underlie the observed cognitive dysfunction. Therefore, the primary aim of this thesis was to evaluate the relationship between health/ treatment, psychosocial, and endocrine-related factors and cognitive dysfunction after breast cancer treatment. In addition, a smaller secondary aim was to assess the appropriateness of different methods of individual change. Chapter 1 provides a brief overview of the structure and content of the thesis. Chpaters 2 and 3 are review papers that evaluate whether there is evidence that variations in psychosocial adjustment, health and treatment factors result in cognitive changes after chemotherapy. Based on previous research, the mechanisms evaluated are endocrine-related changes (use of adjuvant endocrine treatment and chemotherapy-induced menopause); chemotherapy-induced anaemia; depression; anxiety; fatigue; quality of life; and other treatment factors (e.g. treatment duration, time since treatment, tumour stage, use of concomitant medications and co-morbid medical conditions). The impact of confounding variables such as age of participants, level of baseline functioning and methodological limitations are also considered. These two chapters have been published (refer to Appendix A for a complete list of presentations and publications arising from this thesis). The fourth and fifth chapters are methodological in nature. Chapter 4 describes methods, while Chapter 5 is a brief paper (under review) which examines methodological considerations regarding analysis of individual change in neuropsychological performance over time and across domains for women undergoing treatment for breast cancer. The sixth and seventh chapters involve empirical analyses of the data collected as part of the Cognition in Breast Cancer (CBC) study, a longitudinal study examining the causes of variation in cognitive functioning, health and well-being in women up to 2 years post-chemotherapy. Chapter 6 was an experimental study designed to investigate the acute effects of psychosocial mechanisms on cognitive functioning after chemotherapy in a sample of 157 breast cancer patients. Many of the methodological limitations identified in the review studies were addressed and the neuropsychological performance of two groups was compared, namely recently diagnosed breast cancer patients scheduled for chemotherapy (n = 136) or other forms of treatment (n = 21). Participants were assessed prior to commencing treatment and approximately one month post completion of chemotherapy (or 6 months after the first assessment). Individual cognitive impairment was examined using the Reliable Change Index, while Pearson correlations were utilised in order to investigate the effect of psychosocial and health factors on cognitive change. The results indicated that decline in haemoglobin levels and increased anxiety over the course of chemotherapy significantly predicted impairment in multiple cognitive measures, while change in specific cognitive measures was significantly associated with baseline measures of fatigue, depression and functional well-being. The impact of these findings on rehabilitation strategies for women after chemotherapy was discussed. Chapter 7 investigated whether endocrine-related changes, namely chemotherapy-induced menopause and adjuvant endocrine treatment, resulted in increased cognitive dysfunction. One hundred and thirty-six breast cancer patients were assessed using a comprehensive neuropsychological assessment over three time-points, namely pre-chemotherapy, one month and six months post chemotherapy (or at similar time-points). Linear mixed models evaluated the effects of these two factors, with little evidence found to suggest that endocrine-related factors contribute to cognitive dysfunction in breast cancer patients. Chapter 8 comprises a brief summary and overview of the entire thesis and offers overarching conclusions, strengths and weaknesses, and directions for future research. The findings of the present investigations attempt to elucidate the contributions of potentially important psychosocial and health/ treatment-related mechanisms for cognitive dysfunction after breast cancer treatment. While there was little evidence to suggest endocrine-related changes impacted on cognition, the findings linking chemotherapy-induced anaemia and baseline psychosocial measures may play an important role in identifying and treating at-risk individuals. These findings have potential research implications for the ways data is collected, analysed and presented in empirical research as well as clinical ramifications for how women are affected cognitively as well as psychologically by treatment for breast cancer.

Introdução: O aumento de peso corporal e o IMC entre 25 e 29,9 kg/m2 (risco de obesidade) ou 30 kg/m2 (obesidade), no momento do diagnóstico do câncer de mama, são fatores de risco, reconhecidos, para a recidiva da doença e redução do tempo de vida das mulheres. Objetivo: verificar os efeitos da quimioterapia adjuvante sobre o peso e índice de massa corporal de mulheres com câncer de mama. Métodos: o estudo foi descritivo, exploratório, com coleta de dados, a partir de prontuários e contato telefônico, de uma amostra de conveniência de 66 mulheres, com câncer de mama, e submetidas à quimioterapia adjuvante, no período de 2000 a 2008. As variáveis de estudo foram peso e índice de massa corporal, protocolo quimioterápico, número de ciclos de quimioterapia, fase do climatério (pré e pós-menopausa), ingestão alimentar e prática de atividade física. A análise estatística foi realizada por meio dos testes qui-quadrado, t-Student e ANOVA. Foi adotado nível de significância de 0,05 e intervalo de confiança de 95%. Resultados: as mulheres tinham, em média, 49 anos de idade (26 - 75 anos), sendo que a alteração de peso corporal foi associada, significativamente (p < 0,05), com número de ciclos de quimioterapia e alteração da prática de atividade física, enquanto o protocolo quimioterápico, a fase do climatério e a ingestão alimentar não alteraram, significativamente, o peso corporal; não houve diferença, estatisticamente significante, entre IMC, no início da quimioterapia, e as demais variáveis do estudo. Conclusões: o maior o número de ciclos e a prática de atividade física foram estatisticamente significantes, com alteração do peso corporal. / Introduction: The increase of body weight and the BMI between 25 to 29,9 kg/m2 (overweight) or 30 kg/m2 (obese), at the moment of breast cancer diagnosis, are factors of risk, acknowledged, for the recurrence of disease and reduction of survival. Objective: to access the effects of adjuvant chemotherapy on body weight and body mass index in women with breast cancer diagnosis. Methods: the study was descriptive, exploratory, with data collected from medical record and phone contacts with women diagnosed breast cancer, which had undergone adjuvant chemotherapy between 2000 and 2008. The study variables were body weight and body mass index, chemotherapy regimens, number of cycles of chemotherapy, menopausal status (pre and pos menopause), dietary intake and physical activity. The statistical analysis was done by qui-square, t-Student and ANOVA. The significance level adopted was 0,05 and the confidence interval was 95%. Results: 66 women were analyzed, averaging 49 years old (26 to 75 years old), and the body weight difference was associated, significantly (p < 0,05), to the number of cycles of chemotherapy and changes in the physical activity practice, while the chemotherapy regimens, menopausal status and the dietary intake didnt change the body weight significantly; there was no statistically significant difference between BMI, in the beginning of chemotherapy and others variables.Conclusions: number of cycles and physical activities practice were statistically significant, with changes in body weight.

Bakgrund Bröstcancer är den vanligaste cancerformen globalt bland kvinnor. Både den som insjuknat och dennes eventuella närstående drabbas av sjukdomens följder. En behandlingsform är adjuvant cytostatika vilket ofta resulterar i en mångfacetterad biverkningsprofil. Vid pågående cancerbehandling kan fysisk aktivitet lindra både symtom och biverkningar och bör därför föreslås av hälso- och sjukvårdspersonal. Utifrån egenvårdsteorin formulerad av Dorothea Orem betonas särskilt sjuksköterskans funktion i att stödja varje individs förmåga att agera på sätt som främjar dennes fysiska och psykiska mående. Således har fysisk aktivitet, en form av egenvårdsåtgärd, potential att förbättra livskvaliteten för dennagrupp och bör därmed vidare undersökas. Syfte Syftet var att beskriva kvinnors upplevelser av fysisk aktivitet under adjuvant cytostatikabehandling vid bröstcancer. Metod En icke-systematisk litteraturöversikt som baserades på 16 vetenskapliga artiklar med kvantitativ ansats (9), kvalitativ ansats (6) och mixed-method (1). Artiklarna inhämtades från CINAHL och PubMed. Artiklarna genomgick kvalitetsgranskning utifrån Sophiahemmet Högskolas bedömningsunderlag för vetenskaplig klassificering och kvalitet. Resultatet sammanställdes och analyserades med hjälp av integrerad analys. Resultat Resultatet sammanställdes i fyra huvudkategorier: Upplevelser av psykisk hälsa och ohälsa, Symtomupplevelser, Upplevelser av externa resurser samt Upplevelser av vad som försvårar utövandet av fysisk aktivitet. Resultatet belyser att fysisk aktivitet kan bidra med upplevda positiva och negativa aspekter; både gällande psykisk hälsa men även fysisk symtombild. Vidare framkommer att adekvat information, motivation och stöd är avgörande för ett fortsatt utövande av fysisk aktivitet. Slutsats Resultatet visar på en kombination av inre och yttre faktorer vilka gemensamt påverkar den individuella förmågan och nyttan av utförandet av fysisk aktivitet. Det framkommer att egenvård har en betydande roll samt att information och stöd från såväl hälso- och sjukvårdspersonal som närstående är en viktig del i att bibehålla fysisk aktivitet. / Background Breast cancer is the most common cancer type globally amongst women. Both the afflicted and potential close relations face the consequences of the illness. Possible treatment strategies include adjuvant chemotherapy, which has a multifaceted side effect profile. During ongoing treatment healthcare personnel should suggest simultaneous practice of physical activity given its alleviating outcome on symptoms and side effects. The self-care deficit nursing theory by Dorothea Orem emphasizes the nurses’ function in supporting the individuals’ abilities in performing actions towards better physical and mental health. Therefore physical activity, a self-care measure, has the potential of improving the quality of life amongst these women and should be explored further. Aim The aim of this study was to describe the experiences of physical activity in women with breast cancer undergoing adjuvant chemotherapy.  Method A non-systematic literature review based on 16 scientific articles with a quantitative method (9), qualitative method (6) and mixed-method (1). Articles were retrieved from two databases, CINAHL and PubMed, and underwent a quality review based on Sophiahemmet University assessment basis for scientific classification and quality. Results were compiled and analysed with an integrated data analysis. Results When compiling the results four main categories were identified: Experiences of mental health and mental illness, Experiences of symptoms, Experiences of external resources and Experiences of factors aggravating the pursuance of physical activity. Results showed that physical activity can contribute to both positive and negative experiences; concerning mental health as well as physical symptoms. Furthermore adequate information, motivation and support are deemed essential to contribute to continued physical activity. Conclusions Results showed a combination of internal and external factors contributing towards the individual ability and benefit of physical activity. It is indicated that self-care plays a considerable role alongside information and support from health care professionals and close relations in maintaining physical activity.

A luz ultravioleta (UV) bloqueia a replicação e transcrição devido à formação de lesões que distorcem o DNA. Descobrimos que a depleção da quinase ATR promove a indução precoce de apoptose após irradiação com luz UVB em fibroblastos humanos imortalizados com SV40 e que mesmo células proficientes em reparo de DNA e síntese translesão foram incapazes de alcançar a mitose após depleção de ATR. Essa quinase também representa um alvo promissor para sensibilizar tumores com mutações em p53 ao quimioterápico cisplatina e ao indutor de estresse oxidativo cloroquina. Além do bloqueio da replicação, danos no DNA bloqueiam a síntese de RNA. Utilizamos sequenciamento para mapear RNA nascentes e analisar a recuperação da transcrição em escala genômica. Genes mais longos são mais inibidos por luz UV, mas o nível de expressão gênica não contribui para a recuperação da transcrição. Além disso, o reparo de DNA é similar entre genes com recuperação da transcrição distinta e outras regulações, além da remoção de lesões no DNA, devem existir para que a síntese de RNA recomece. / Ultraviolet (UV) light stalls replication and transcription due to the formation of lesions that distort DNA. We found that ATR silencing promotes early induction of apoptosis after UVB light in human fibroblasts immortalized with SV40 and even cells proficient in DNA repair and translesion synthesis were unable to reach mitosis after ATR depletion. This kinase is also a promising target for sensitizing tumors with p53 mutations to chemotherapeutic that block replication, such as cisplatin, and the oxidative stress inducer chloroquine. In addition to blocking the replication, DNA damage arrest the synthesis of RNA. We used next-generation sequencing to map and analyze the nascent RNA transcription recovery genome-wide. We confirmed that longer genes are more inhibited following UV light, however, the level of gene expression does not contribute to the recovery of transcription. Moreover, DNA repair is similar among genes with different recovery of transcription and further regulation, besides DNA damage removal, must exist to promote resumption of RNA synthesis.

A luz ultravioleta (UV) bloqueia a replicação e transcrição devido à formação de lesões que distorcem o DNA. Descobrimos que a depleção da quinase ATR promove a indução precoce de apoptose após irradiação com luz UVB em fibroblastos humanos imortalizados com SV40 e que mesmo células proficientes em reparo de DNA e síntese translesão foram incapazes de alcançar a mitose após depleção de ATR. Essa quinase também representa um alvo promissor para sensibilizar tumores com mutações em p53 ao quimioterápico cisplatina e ao indutor de estresse oxidativo cloroquina. Além do bloqueio da replicação, danos no DNA bloqueiam a síntese de RNA. Utilizamos sequenciamento para mapear RNA nascentes e analisar a recuperação da transcrição em escala genômica. Genes mais longos são mais inibidos por luz UV, mas o nível de expressão gênica não contribui para a recuperação da transcrição. Além disso, o reparo de DNA é similar entre genes com recuperação da transcrição distinta e outras regulações, além da remoção de lesões no DNA, devem existir para que a síntese de RNA recomece. / Ultraviolet (UV) light stalls replication and transcription due to the formation of lesions that distort DNA. We found that ATR silencing promotes early induction of apoptosis after UVB light in human fibroblasts immortalized with SV40 and even cells proficient in DNA repair and translesion synthesis were unable to reach mitosis after ATR depletion. This kinase is also a promising target for sensitizing tumors with p53 mutations to chemotherapeutic that block replication, such as cisplatin, and the oxidative stress inducer chloroquine. In addition to blocking the replication, DNA damage arrest the synthesis of RNA. We used next-generation sequencing to map and analyze the nascent RNA transcription recovery genome-wide. We confirmed that longer genes are more inhibited following UV light, however, the level of gene expression does not contribute to the recovery of transcription. Moreover, DNA repair is similar among genes with different recovery of transcription and further regulation, besides DNA damage removal, must exist to promote resumption of RNA synthesis.

Purpose: to evaluate if there is a difference between adjuvant chemo-endocrine therapy (QHT) and hormone therapy (HT) alone in ten years overall survival (OS) in post-menopausal women with early stage luminal A breast cancer Methods: A non concurrent cohort study was conducted in a cancer treatment center in Peru, we measured demographic and clinical-pathologic anatomy variables. Log-rank test and a Kaplan-Meier (KM) curve were performed to evaluate ten years OS. Cox regression analysis was used and hazard ratio were reported with confidence intervals 95% (95%CI) for crude and adjusted by the significant variables in the bivariate analysis. The fullfilment of hazard proportionality was evaluated by Schoenfeld residuals method and graphic method. Results: 65 patients received adjuvant chemo-endocrine therapy and 140 only received hormone therapy. Ten years OS was 77% for QHT and 84% for HT, this difference was not significant when using KM and log-rank; age at diagnosis (p=0,01), clinical status (p=0,02), tumor size (p=0,04), positive estrogen receptor (p=0,03), node status (p=0,012) and type of surgery (p=0,03) were statistically significant when compare with OS. When proportional hazards assumption was evaluated (SPH), only the period of time after two years of following was satisfied, cox models were created for this period of time. Crude HR for ten years OS was 1,48 (CI95%:0,65-3,39). First model adjusted HR was 1,83 (CI95%:0,64-5,30) and second model adjusted HR was 1,77 (CI95%:0,64-4,90). Conclusions: There was no significant difference in ten years OS between both courses of treatment evaluated in post-menopausal women with luminal A breast cancer. / Objetivo: evaluar si existe diferencia en la supervivencia global (SG) a diez años entre la quimioterapia adyuvante asociada a hormonoterapia (QHT) frente a la hormonoterapia sola en mujeres posmenopáusicas diagnosticadas con cáncer de mama luminal A (CMLA) en estadio temprano. Métodos: se realizó un estudio cohortes no concurrente en un centro de atención oncológica en Perú. Se incluyeron variables demográficas y clínico-patológicas. Para comparar la SG se utilizó la curva de Kaplan-Meier (KM), test de log-Rank y la regresión de Cox para estimar el Hazard Ratio (HR) con intervalos de confianza 95% (IC95%) tanto crudos como ajustados por las variables asociadas durante el análisis bivariado. Se evaluó el cumplimiento del supuesto de proporcionalidad de hazard (SPH) con el método de residuos de Schoenfeld y método gráfico. Resultados: 65 pacientes recibieron QHT y 140 sólo hormonoterapia. La SG a los diez años fue 77% y 84% para QHT y HT respectivamente, esta diferencia no fue significativa al utilizar KM y test de log-Rank; no obstante la edad (p=0,01), estadio clínico (p=0,02), tamaño tumoral (p=0,04), receptor estrogénico positivo (p=0,03), número de ganglios (p=0,012) y tipo de cirugía (p=0,03) resultaron asociadas significativamente a la supervivencia global a los diez años. Cuando se evaluó el SPH se evidenció que sólo se cumplía tras los dos años de seguimiento, por lo que se generaron modelos de Cox en éste periodo. El HR crudo a los diez años fue de 1,48 (IC95%: 0,65-3,39). En el modelo ajustado uno se observó un HR de 1,83 (IC95%: 0,64-5,30) y para el segundo modelo ajustado un HR de 1,77 (IC 95%: 0,64-4,90). Conclusiones: no se encontró diferencia significativa en la SG a los diez años entre los esquemas terapéuticos evaluados en mujeres posmenopáusicas con CMLA.