Association of prediagnostic physical activity with survival following breast cancer diagnosis: influence of TP53 mutation status

Abstract

Purpose Physical activity both before and after breast cancer diagnosis has been associated with improved survival. However, it is not clear whether this association differs by molecular features of the tumor or by recency of the physical activity to the time of diagnosis. Methods We examined the association of prediagnostic physical activity with survival in a cohort of 1,170 women with primary, incident, and histologically confirmed breast cancer, examining tumor molecular subtypes. Cox regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI). Results Mean follow-up time was 87.4 months after breast cancer diagnosis; there were 170 deaths identified. Compared with inactive patients (<3 hours/ week), women with higher average lifetime physical activity (>6 hours/ week) had reduced risk of all-cause mortality (adjusted HR = 0.61, 95% CI, 0.40-0.95; p trend = 0.04). There were no clear differences in the associations for lifetime and more recent physical activity. Lifetime physical activity was also weakly associated with decreased risk of breast cancer-specific mortality. Higher lifetime physical activity was associated with reduced risk of all-cause mortality among women with ER-positive tumors (HR = 0.52, 95% CI, 0.29-0.93), and mutant TP53 tumors (HR = 0.22, 95% CI, 0.06-0.72); however, no statistically significant interactions were observed for ER or TP53 status. Conclusions Our study further supports that prediagnostic physical activity improves overall survival following breast cancer, and suggests that the associations of prediagnostic physical activity with survival following breast cancer may vary by molecular features of the tumor, particularly ER and TP53 status.

Physical Exercise and Gene p53—A Mini Review

“…Physical activities, mainly of moderate-intensity are known to improve the oxidative mitochondrial capacity and promoting activity of enzymes that are responsible for oxidation of glucose and acid fatty and may lead to a dispute by glucose, thereby decreasing availability supply to the tumor cells and the influence of mutated p53 gene, which plays an apparent role of enhancing the function of these cells [9].…”

“…Exercise seems to have a key role in this role p53, since several studies have shown that this protein reacts to stress caused by physical exercise, the data type of stimulation can increase or decrease its nuclear expression, mitochondrial and cytoplasmic, was also reported its ability to prevent or facilitate translocation of p53 to the nucleus mitochondria [14]. In an attempt to clarify some cases, studies of the area, selected for this systematic review, seek to work with different scenarios, such as the TP53 transmutation of studying cancer patients having the mutation, working with knocked out mice, cell handling "in vitro" [9].…”

“…The monitoring of the level of physical activity throughout the life of women diagnosis of breast cancer, mostly with mutations in TP53, showed a reduction in mortality risk associated with those practiced years Physical 1 -10 and 10 -20 years before diagnosis [9]. Corroborating these findings, experiments with rats, demonstrate that those exercised voluntarily (treadmill at 17.5 to 20 m/min), the period prepubescent, resulted in lower risk of development of triggers malignant transformation of breast tissue and improves the regulation of p53, while on sexual maturation, compared to the group of rats that did not exercise [14].…”

“…In the case of TP53 mutation, which results in the inactivation of p53 is one reported change in cell bioenergetics, it is more dependent on glycolysis and It has functionality drop in mitochondrial respiration, a process is known as Warburg effect, which could explain in part as a stimulus similar exercise results in different response in the presence or absence of mutated TP53 [9]. This decrease in mitochondrial function, previously reported, is confirmed in mice homozygotes, who also develop sarcomas and have a higher incidence of metastasis [15].…”

Study protocol for a nationwide questionnaire survey of physical activity among breast cancer survivors in Japan

“…Some healthy behaviours, such as moderate physical activity, a healthy diet and maintenance of a healthy body weight, may lower the risk of recurrence and improve survival 2. In particular, a high level of physical activity is related to the extension of healthy lifespan3–9 and improvement of HRQOL among breast cancer survivors 3–9. Thus, international and Japanese clinical practice guidelines strongly recommend that survivors maintain high levels of physical activity 8 10.…”