Efficacy of Exercise on Breast Cancer Outcomes: A Systematic Review and Meta-analysis of Preclinical Data

Abstract

The use of preclinical models to investigate antitumor effects of exercise on breast tumor (BT) development and progression are critical. However, published results have not been quantitatively summarized or examined for potential exercise-moderating variables. We conducted this review to summarize and quantify the effect-size of exercise on BT outcomes in preclinical studies. A literature search was performed in MEDLINE, PubMed, Web of Science and System for Information on Grey Literature in Europe (SIGLE) databases. Risk of bias was assessed using SYRCLE's RoB tool. A total of 116 correlations were performed to analyze 28 preclinical studies published through December 2016, which included 2,085 animals and 51 exercise programs. Positive effects of small, medium and large magnitude were observed in tumor incidence, growth and multiplicity, respectively. In the tumor microenvironment, positive effects of large magnitude were also observed in proliferation and apoptosis but not in angiogenesis. Moderator variables correlated with higher intervention effects were identified along with a considerable heterogeneity in exercise protocols that precluded us from clearly perceiving the benefits of exercise exposure. In conclusion, exercise performed under specific conditions benefits BT outcomes. Preclinical studies with exercise designs mimicking exercise exposure that can be used in clinical contexts are needed.

Exercise Training-induced Modulation in Microenvironment of Rat Mammary Neoplasms

“…Several studies have shown that expos-ing breast cancer patients to regular physical exercise benefits prevention, recurrence, and survival but the biological mechanisms underlying these benefits remain unclear [17,34]. The role of exercise in the breast cancer continuum is unclear despite convincing clinical epidemiological data confirming its efficacy with contrasting results in animal models [9]. In addition, knowledge about the tumor microenvironment (TME) during exercise is lacking [2].…”

Exercício físico aeróbico de intensidade moderada reduz a velocidade de crescimento e modula o metabolismo energético tumoral em modelo experimental de câncer de mama triplo-negativo

“…Até o momento nenhuma terapia específica para o TNBC está disponível na prática clínica e a terapia padrão para este tipo molecular de câncer inclui agentes como taxanos, antraciclinas e ciclofosfamida (Yao et al, 2017). Outras estratégias terapêuticas incluem o uso de inibidores da polimerase de ribose poli ADP (inibidores da PARP), inibidores de receptor do fator de crescimento epidérmico (EGFR), agentes antiangiogênicos (Anders e Carey, 2008;Aysola et al, 2013;Yao et al, 2017), inibidores de receptores tirosina quinase, inibidores mTOR, além do interesse no papel dos compostos de platina, incluindo carboplatina e cisplatina (Yao et al, 2017) (Speck et al, 2010;Ballard-Barbash et al, 2012;Brown et al, 2012;Loprinzi et al, 2012;Figueira et al, 2018;Wirtz e Baumann, 2018).…”

“…Nesse sentido, estudo de meta-análise envolvendo roedores demonstrou que a intensidade do exercício físico parece ser determinante para a modulação da tumorigênese, com benefícios acumulados em sessões com exercícios de intensidade moderada ou vigorosa, e duração de 30 a 45 min, com frequência de cinco vezes por semana (Figueira et al, 2018).…”

“…Há mais de duas décadas, a pesquisa em modelo experimental de carcinogênese mamaria induzida quimicamente, demonstrou que a intensidade e duração do exercício físico afetam o desenvolvimento do câncer de mama (Thompson, 1994;Figueira et al, 2018).…”

“…Contudo, apesar da intensidade parecer um fator determinante na modulação dos desfechos tumorais no câncer de mama e também outros tipos de tumor, em geral, os resultados dos estudos não apresentam resultados significativos sobre a quantidade ideal de exercício (i.e. intensidade, duração e frequência) para obter benefícios (Figueira et al, 2018). Além disso, em modelos experimentais a quantidade de células inoculadas no animal também pode ser um fator determinante para a resposta anti-tumorigênica do exercício físico.…”