Evaluation of the impact of physical exercise on quality of life and clinical outcomes among women undergoing treatment for breast cancer

This is a cohort, longitudinal, observational and prospective study, aiming to evaluate the impact of physical exercise in the oncological treatment of patients with breast cancer. The recruitment of participants for the study has been carried out by convenience, with the target population being patients participating in the Clinical Outcomes Program from HMV. The inclusion criteria for the present study were: women over 18 years old, with a confirmed diagnosis of breast cancer, without previous treatment and who started their cancer treatment at the institution of interest, which may be surgical, chemotherapy, radiotherapy or hormone therapy. There was no restriction on participation in the study by type of breast cancer, staging or type of treatment, as the clinical profile of patients treated at the hospital's oncology service is very heterogeneous and each patient receives an individualized treatment plan according to their needs and demands. In addition to that, it has been required for those patients to answer the questionnaire during the period of diagnosis, ongoing treatment and after 6 months of treatment. Foreign patients, patients who had already started treatment, relapses and rare tumors were excluded from the study.

The data collection period has been carried out between November 2018 and July 2022. Every time a patient meeting the inclusion and exclusion criteria was included in the Clinical Outcomes Program, a member of the assessment team was responsible for contacting them in order to verify their interest in participating in the study. The initial contact was carried out through telephone calls with the help of research assistants, and also in face-to-face appointments at the Nucleo Mama, by a nursing professional. If the patient manifests interest in participating in the study, the term of free and informed consent was provided, and the main study objectives and procedures were presented and discussed in detail. After signing the term, a trained member of the research team conducted the interview for data collection, the survey forms followed the International Consortium for Health Outcomes Measurement (ICHOM) methodology. All data was collected and stored by using the Research Electronic Data Capture (RedCap) software database.

The main data for the present study was collected through a semi-structured questionnaire, which has been validated using the ICHOM methodology.9 This questionnaire presents the following measures:

Six months after starting treatment, all included participants received a telephone call in order to reapply the same questionnaire. The follow-up times for each patient were described as T0 (data collected right after diagnosis of breast cancer) and T180 (data collected 6 months after initiation of treatment).

The study protocol has been approved by the Ethics Committee (CEP) and all patients have had a free and informed consent form signed. The data collected from each patient has been used only for research purposes.

Initially, the data were dozwnloaded in Excel format, and submitted into SAV format, in order to carry out the statistical analyses using the SPSS software version 21.0 (IBM SPSS Statistics). The QoL questionnaire has been divided into scores for physical, emotional, social, cognitive, pain, fatigue, and cancer symptoms, creating scores for each health condition.

Qualitative variables have been described using absolute and relative frequencies. The distribution of continuous quantitative variables has been analyzed using the Shapiro-Wilk test, where all of them have shown an asymmetrical distribution. Therefore, these variables were described by median and interquartile range (IQ). For the general analyses, the study participants were divided into two groups: those without physical exercise after six months of treatment and those with physical exercise after six months of treatment. It has verified the difference in intragroup and intergroup scores at times of T0 and T180. Therefore, the comparison of clinical and QoL scores at T0 and T180 has been performed using the Wilcoxon test. The comparison of scores between the group that has been performing physical exercise and the group that has not been performing physical exercise after six months of treatment was performed using the Mann-Whitney test. Afterwards, in order to identify factors associated with changes in the practice of physical exercise during cancer treatment, the participants have been divided into four groups: never exercised, stopped exercising during treatment, started exercising during treatment and always exercised. The comparison of scale scores between the four groups has been performed using the Kruskal-Walys test.

The correlation between the weekly physical exercise performed by the participants and the clinical scores, as well as QoL has been evaluated using Spearman's correlation test.

Finally, a multiple linear regression analysis has been performed in order to evaluate the association between average factors (age, instructional level, presence of comorbidities), practice of physical exercise and treatment systemic side effects as well as the outcome variables (scales functioning, fatigue and QoL).

All the analysis considered a significance level of 5%.

A total of 196 people agreed to participate in the study. As the research was being carried out, 150 answered the form when they were diagnosed (T0) and also 6-months after starting their treatment (T180). One patient was excluded from the study because he was male. Therefore, a total of 149 participants were included in this study, all female (100.0%), with an average age of 58.0 years old [IQ: 44-68], with the majority of white ethnicity (99.3%). In this regard, 51.7% of the participants had at least one comorbidity and 56.4% reported being in the postmenopausal period. Regarding the histological type of breast cancer, the most prevalent was invasive ductal carcinoma (n=108; 72.5%), and most women were in stage I of the tumor (TNM) (n=93; 62.4%). There was a wide combination of different treatments in the sample; however, the vast majority of participants underwent surgery (n=129; 86.6%), with the surgery being the only treatment resource used in 62 participants. A smaller group of participants received chemotherapy (34.2%) and radiotherapy (24.2%). This smaller group has also had other treatment strategies combined. The details of the other sociodemographic and clinical characteristics of the sample are presented in Table 1.

Regarding physical exercise, considering 149 patients included in the study, 54.4% reported not doing any type of exercises in the period they were diagnosed (T0). After six months of treatment, it has been found that 78 (52.3%) participants were practicing physical exercises and 71 (47.7%) participants did not exercise at all (Graph 1). In this sense, a total of 22 (14.8%) women stopped exercising during the treatment and 32 (21.5%) started practicing physical exercises during the treatment. Among the participants who reported practicing physical exercise six months after starting treatment, the average weekly time of physical activity was 150 minutes.

It was also collected, through direct information, the type of exercise practiced during this period, and 14.7% reported taking more walks. In the average time of practice of physical exercise, we can observe that the practice of running and tennis exercises were performed in an average time of 240 minutes (Table 2).

When intragroup differences were found in QoL scores and clinical outcomes at T0 and T180, it has been observed that the group that were not exercising after six months of treatment presented worse results (T180) for physical performance scores, pain and treatment side effects (Table 3). In emotional, cognitive and functional performance scores, the group showed improvement, and in daily tasks, social, symptoms, fatigue and global health status scores, there was no significant change among the groups. The group that was practicing physical exercise six months after starting treatment showed improvement (T180) for emotional, social, functional performance scores, symptoms, global health status and final QoL score. The scores for physical performance, daily tasks, cognitive, symptoms, fatigue, pain and treatment side effects did not show any significant changes (Table 3). Lastly, comparing the scores between the group that practiced and the group that did not practice exercises, it was possible to observe that the group practicing exercises presented better results in all domains, with the exception of the cognitive and social performance score.

To verify the impact of changes in physical exercise behavior during treatment on clinical outcomes, the two groups were subdivided into four groups, namely: never exercised (n=49), stopped exercising during treatment (n=22), started exercising during treatment (n=32) and always did physical exercise (n=46). Comparison between groups for each of the QoL domains are presented in Figure 1.

The scores for physical, social, emotional performance, daily tasks and the sum of the scores showed that those who have always exercised had better results, followed by those who had started exercises during treatment, those who never exercised and finally those who stopped exercising during the treatment. The scores for pain, fatigue and cancer symptoms showed that adverse reactions were higher in those who stopped physical activities during treatment, followed by those who never started any type of physical activities, those who started it during treatment and finally those who had regular physical activities.

The time of weekly physical exercise after six months of treatment showed a significant direct correlation with physical performance (ρ=0.288, p<0.001), daily tasks (ρ=0.288, p<0.001), emotional performance (ρ=0.206, p=0.012), performance score (ρ=0.213, p=0.009), global health status (ρ=0.209, p=0.011) and the sum of QoL scores (ρ=0.219, p=0.007), as shown in Table 4. There was a significant inverse correlation between physical exercise time and fatigue scores (ρ=-0.241, p=0.003), pain (ρ=-0.205, p=0.012) and symptoms (ρ=-0.275, p<0.001). The weekly physical exercise time did not present a significant correlation with the scores of cognitive performance (ρ=0.001, p=0.987) and social performance (ρ=0.059, p=0.475).

Through linear regression analysis, the association of sociodemographic variables, physical exercise practice, presence of comorbidities and systemic side effects was evaluated for treatment with the domains of physical performance, fatigue, daily tasks and the total QoL score, according to Tables 5 and 6. In regard to the systemic side effects of the treatment, symptoms of dry mouth, different taste than usual, irritated and/or painful eyes, hair loss, hot flashes and indisposition were evaluated. For analysis, complete primary education was presented as a reference in relation to secondary and higher education.

All models presented satisfactory parameters. The regression models performed for physical performance, fatigue, and daily tasks were able to explain 25.1%, 21.2%, and 17.2% of the outcome variance, respectively. In these three models, the significant variables for predicting the outcomes were the practice of physical exercise and systemic side effects of the treatment. As a result, it has been observed that the practice of physical exercise increases an average of 5.5 points in the physical performance scores (p=0.01), and also increases an average of 8.2 points in the daily tasks scores (p=0.008) and decreases an average of 5.3 points in fatigue scores (p=0.038). In the model for QoL scores, physical exercise lost significance. On the other hand, treatment side effects showed significance (p<0.001) in all regression models presented.