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- Effects of physical exercise concomitant with chemotherapy on cardiac functionality of women with breast cancerPublication . Antunes, Pedro Miguel da Silva; Esteves, Maria Dulce Leal; Ascensão, António Alexandre Moreira Ribeiro de; Sampaio, Francisco Pedro Morais Dias de AlmeidaAnthracycline-containing chemotherapy is commonly used in the treatment of hematologic cancers and solid tumors, including breast cancer. Despite its wellrecognized clinical efficacy, the use of anthracyclines is limited by dose-dependent and cumulative cardiotoxic risk. Additionally, breast cancer treatment is often multimodal, which can further increase the cardiac damage. The cardiac toxicity poses significant challenges, influencing therapeutic decision-making and exacerbate patients’ morbidity and mortality. Longitudinal studies have shown that cardiovascular diseases are one of the leading causes of death among women with breast cancer. As a result, various international agencies, such as the American Society of Clinical Oncology and the European Society of Cardiology, emphasize the importance of implementing primary prevention interventions. Exercise training is an accessible and cost-effective intervention with well-documented benefits for overall health. Preclinical studies have shown promising results in mitigating the cardiotoxic impact of anthracyclines. However, whether this potential cardioprotective effect translates to humans is a question that remains to be clarified. The objectives of this thesis were to conduct a literature review on this topic (Study 1 and 2) and, as the core of this doctoral program, to design a single-center, randomized controlled trial with two arms (exercise group vs. usual care group) (Study 3). The main objective of this trial was to analyze the impact of a supervised exercise training program on established markers of cardiac toxicity (i.e., left ventricular ejection fraction, global longitudinal strain, and cardiac biomarkers) in women with breast cancer undergoing curative anthracycline-containing chemotherapy. Secondary objectives included analyzing the safety of exercise training and its effect on cardiorespiratory fitness, physical functionality, and health-related quality of life. The program consisted of three sessions per week of combined training (i.e., aerobic and resistance training) during each participant's chemotherapy length (approximately 5- months). Through the literature review, supported by a systematic review with metaanalysis of randomized controlled trials (Study 2), we found that evidence on the effect of physical exercise on established parameters of cardiac toxicity was limited, as only four eligible studies were identified. Most of these studies had significant limitations, including designs not specifically aimed at evaluating the efficacy of physical exercise on the parameters of interest, small sample sizes, short training programs, and brief followup periods. The results of the meta-analysis did not show a significant effect of exercise training compared to non-exercise. However, an exploratory analysis, which included studies with training programs consisting of at least 36 sessions (n=3), revealed a superior effect of exercise training on resting left ventricular ejection fraction. This suggests that the length of the exercise training programs might be associated with the effect of exercise training on cardiac function. The results of the randomized controlled trial demonstrated that exercise training did not significantly prevent the decline in established markers of cardiac toxicity compared to control (Study 4). However, it was found that exercising was safe—no serious adverse events were reported during the exercise training sessions—and it significantly prevented the decline in cardiorespiratory fitness, physical functionality, and health-related quality of life (Study 4 and 6). Additionally, we found that the response of cardiorespiratory fitness among participants randomized to the exercise group was heterogeneous, which justified the analysis of potential predictors through an exploratory study (Study 5). The results revealed that the parameters associated with the response in cardiorespiratory fitness to training were baseline body mass index and total aerobic training metabolic equivalent of task per hour (MET-hour). In summary, the results of this thesis suggest that adding exercise training to standard breast cancer care does not provide benefits on established markers of cardiac toxicity in women undergoing anthracycline-containing chemotherapy. However, the findings of experimental works indicate that implementing a supervised exercise training program during chemotherapy is safe and can be a viable and effective approach for improving cardiorespiratory fitness, preventing the decline in physical functionality and healthrelated quality of life in this challenging patient population. Additionally, our study suggests that the total energy expenditure of aerobic exercise (i.e., MET-hour) may be a predictor of cardiorespiratory response.
- Avaliação dos efeitos de um programa de exercício físico na aptidão física e na qualidade de vida de sobreviventes de cancro da mamaPublication . Antunes, Pedro Miguel da Silva; Esteves, Maria Dulce Leal; Moutinho, José Alberto FonsecaO cancro da mama é o tipo de cancro mais diagnosticado em mulheres, registando-se mais de 1.3 milhões de casos por ano a nível mundial. Nas últimas décadas, o tratamento do cancro da mama teve progressos substanciais, com consequente aumento do número de sobreviventes. Apesar dos resultados do tratamento serem maioritariamente positivos, há a considerar efeitos colaterais a nível físico e psicológico, comprometendo a capacidade e a funcionalidade diária destas pacientes. Os efeitos físicos incluem fadiga, diminuição da capacidade aeróbia, da força muscular, da amplitude do movimento, alteração da composição corporal, comprometendo inevitavelmente a qualidade de vida. Atualmente, existem evidências científicas que o exercício físico exerce um papel não farmacológico, efetivo na recuperação após cirurgia e tratamento na gestão dos sintomas associados à doença e ao tratamento. Baseada nesta hipótese, foi criado o programa piloto MAMA_MOVE. Esta investigação teve como objetivo principal avaliar os efeitos do treino combinado na aptidão física (AP) e na qualidade de vida em sobreviventes de cancro da mama (SCM). Neste estudo, onze doentes formaram o grupo intervenção, que participou no MAMA_MOVE, enquanto oito formaram o grupo de controlo. Após 16 semanas, foram verificadas, pelo GI, melhorias significativas (p <0.05) em todas as variáveis apresentadas. Estes resultados demostram que a o exercício físico exerce um papel determinante na melhoria da AP e da qualidade de vida em SCM. O MAMA_MOVE pretende ser um coadjuvante terapêutico eficaz na recuperação e melhoria da AP, da fadiga e da qualidade de vida. Este programa integra 3 sessões semanais de treino combinado, supervisionado, específico, orientado para mulheres SCM, com intensidade progressiva, decorrendo durante 4 meses na Universidade da Beira Interior. Ao longo do estudo foram realizadas 3 avaliações (inicial, decorridas 8 e 16 semanas), tendo sido medida indiretamente a força muscular dos membros inferiores pelo sit-stand test, a força de preensão por um dinamómetro manual, a capacidade aeróbia pelo protocolo de Blake modificado e a qualidade de vida pelo European Organisation for Research and Treatment Cancer Core Quality of Life Questionary C30.
- Impact of exercise training on cardiotoxicity and cardiac health outcomes in women with breast cancer anthracycline chemotherapy: a study protocol for a randomized controlled trialPublication . Antunes, Pedro Miguel da Silva; Esteves, Dulce; Nunes, Célia; Sampaio, Francisco; Ascensão, António; Vilela, Eduardo; Teixeira, Madalena; Amarelo, Anabela Leal; Joaquim, AnaAnthracyclines are chemotherapeutic agents frequently used in breast cancer (BC) treatment. Although it improves disease-free and overall survival, the use of anthracyclines is associated with a cumulative risk of cardiac toxicity. Preventive strategies to optimize cardiac health are needed and exercise is proposed as a potential non-pharmacological approach for counteracting anthracycline-related cardiotoxicity (ARC). Most of the data on the effects of exercise to reduce ACT are from animal studies, with only a few studies in a limited number of patients indicating beneficial effects. To better understand the effectiveness of exercise in the mitigation of ARC, clinical, real-world trials claim require a larger sample size and more accurate and valuable clinical biomarkers. In this study, we intend to include a large sample and investigate cardiac function through serial measures of biomarkers and imaging techniques.
- Effects of physical exercise on outcomes of cardiac (dys)function in women with breast cancer undergoing anthracycline or trastuzumab treatment: study protocol for a systematic reviewPublication . Antunes, Pedro Miguel da Silva; Esteves, Dulce; Nunes, Célia; Amarelo, Anabela; Moutinho, José Fonseca; Afreixo, Vera; Costa, Henrique; Alves, Alberto; Joaquim, AnaCardiotoxicity is a known complication and one of the most adverse effects from the use of conventional treatments such as anthracyclines and trastuzumab in breast cancer (BC) care. This phenomenon has been associated with the restriction of therapeutic options and the increase of cardiovascular complications, which may compromise the survival of patients. Implementation of preventive strategies is an important approach for the management of this issue. Physical exercise has been proposed as a non-pharmacological strategy to counteracting cardiotoxicity. The aim of this protocol is to describe the rationale and methods for a systematic review of published randomized controlled trials (RCTs) that have analysed the effects of physical exercise on outcomes of cardiac (dys)function in women with BC undergoing neoadjuvant or adjuvant treatment containing anthracyclines and/or trastuzumab.
- Health-related quality of life and physical fitness in breast cancer patients: the impact of a supervised physical exercise program in women with no exercise experiencePublication . Antunes, Pedro Miguel da Silva; Esteves, Dulce; Nunes, Célia; Joaquim, Ana; Pimentel, Francisco; Moutinho, José FonsecaAfter breast cancer diagnosis (BCD), localized breast cancer (BC) patients are treated with curative intent by several therapeutic modalities. Despite the benefit of those therapies, the induction of side effects is acommon consequence affecting psychosocial and physiological outcomes. This quasi-experimental study compared physical fitness in recent-term (14–30 months; n= 11) and later-term (74–92 months; n= 8) BCD patients. After inclusion, recent-term BCD patients were engaged in asupervised exercise program and was explored its impact on physical fitness, health-related quality of life (HR-QOL) and fatigue. At baseline (M1) and after 8 (M2) and 16 weeks (M3) of this period, HR-QOL and fatigue were evaluated by the EORTC QLQ-C30 questionnaire and physical fitness through the estimation of maximum oxygen consumption (VO2max,ml.kg.min–1), handgrip force (kg) and sit-stand test. At baseline, women with later-term BCD have revealed better VO2max (p < 0.05) than recent-term BCD patients. There was asignificant time*group interaction for physical fitness outcomes and only the patients who have participated in the exercise program reported significant changes between baseline and at 16 weeks. The observed results demonstrated that performing regular exercise is associated with effective psychosocial and physiological recovery after BCD.
- Avaliação dos efeitos de um programa de exercício físico em mulheres sobreviventes de cancro da mamaPublication . Antunes, Pedro Miguel da Silva; Esteves, Dulce; Moutinho, José Fonseca; O'Hara, Kelly; Brás, Rui; Nunes, CéliaPor ano em todo o mundo, são diagnosticados cerca de 1.3 milhões de novos casos de cancro mama. Recentemente, o tratamento do cancro da mama obteve progressos substanciais, com consequente aumento de sobreviventes. No entanto, apesar dos benefícios destes tratamentos, o desenvolvimento de efeitos secundários é uma realidade, destacando-se a fadiga, a diminuição da aptidão física e da qualidade devida. Assim, por estes motivos, torna-se fundamental a criação de intervenções que reduzam ou atenuem os efeitos relacionados com a doença e o tratamento do cancro. Atualmente, a investigação que examina a potencialidade do exercício físico em sobreviventes de cancro da mama te conquistado um maior território no campo científico. A American Cancer Society refere que a inatividade deve ser evitada, sendo aconselhado o regresso às atividades básicas da vida diária o mais rápido possível. De facto, o exercício físico é revisto por vários estudos como u meio não farmacológico, eficaz e seguro na promoção da aptidão e funcionalidade física, na diminuição dos efeitos adversos da doença e dos tratamentos , sobretudo, na melhoria da qualidade de ida. Uma revisão quantitativa de 82 ensaios controlados, relacionados com intervenções de atividade física em sobreviventes de cancro, mostrou que o exercício físico é bem tolerado durante e após o tratamento, sendo estes resultados também suportados por uma roundtable do American College of Sports Medicine. Baseado netas evidencias e com o objetivo de avaliar os efeitos dos exercícios físico na aptidão física e na qualidade de vida em mulheres sobreviventes de cancro da mama foi criado o programa piloto MAMA_MOVE orientado especificamente para esta população. Neste estudo participaram 19 mulheres, com idade entre 30-75 anos e com confirmação clínica de cancro da mama com estágio I-III, tendo 11 constituído o grupo de intervenção e 8 o grupo de controlo. Durante 4 meses o grupo de intervenção realizou 3 sessões semanais de exercício físico aeróbio e de força muscular com intensidade moderada. O estudo abarcou 3 momentos de avaliação (inicial, decorridos 2 e 4 meses) tendo sido medido , em todas as participantes, indiretamente a força muscular dos membros inferiores pelo sit-stand test; a força e preensão; a capacidade aeróbia (VO2máx) e a qualidade de vida pelo EORT QLQ-C30. Em resposta ao treino realizado, foram verificadas no grupo de intervenção melhorias significativas no VO2máx (p <0.05) no sit-stand test (p<0.001) e na força de preensão do lado operado (p<0.05) e do lado não operado (p<0.001) não tendo existido qualquer efeito adverso derivado da prática do exercício físico. Foram ainda observadas melhorias significativas na qualidade de vida (p<0.001) e na funcionalidade física (p<0.001). Por outro lado, no grupo de controlo apenas foram constatadas modificações no sit-stand test (p<0.05). Desta forma, confirma-se que o exercício físico é um coadjuvante terapêutico seguro e eficaz na melhoria da aptidão física e da qualidade de vida me mulheres sobrevivente de cancro.