**4. Discussion**

The aim of the present study was to identify the levels of PA and the perceived QoL, investigating their potential interactions, in females undergoing chemotherapy due to BCa diagnosis, and to compare them with healthy females of the same age.

Our main findings demonstrate that women suffering from BCa and undergoing chemotherapy were willing to exercise and they participated in regular PAs, exhibiting weekly energy expenditure levels similar to those of sex- and aged-matched healthy individuals. However, they preferred to exercise in low or moderate intensities, showing significantly lower levels of MET-min per week expended in high intensity PAs compared with the healthy controls. These findings are in agreemen<sup>t</sup> with previous studies implying that cancer patients demonstrate lower levels of vigorous-intensity PAs post than before diagnosis [26,27]. Even though it has been established that high-intensity activities can safely be performed by cancer patients, offering different health benefits than those derived from the conventional exercise programs, cancer patients appear to hesitate to participate in vigorous PAs [28]. On the other hand, cancer-related fatigue and general pain probably exacerbate the overall burden of the disease and the therapeutic interventions, making participation in more intense physical activities difficult, especially for those patients with more advanced stages of the disease.

Moreover, our study showed that although the BCa patients were exercising in general, they accumulated many hours per day sitting down, not only at work but also at home, since many patients often interrupted their work during chemotherapy sessions, thus spending more hours per day seated at home, which may result in their overweight phenotype. These findings strengthen the evidence from previous studies which supported the hypothesis that an increased BMI is associated with a sedentary lifestyle after cancer diagnosis [29]. Since an increased body weight has been associated with a higher risk of disease recurrence and reduced survival, all cancer patients should not only avoid remaining physically inactive but also they need to follow the specific exercise recommendations, so as to optimize their health exercise benefits [30].

Regarding the QoL, our study showed that BCa patients exhibited moderate levels of perceived QoL, similarly to the control group. More specifically, a strong negative correlation was found between QoL and fatigue as expected, highlighting the fact that cancer-related fatigue remains a huge barrier to patients' daily life [31,32]. In addition, negative correlations were also found between physical functioning and the side effects of the disease, such as pain, fatigue and dyspnea, indicating that these symptoms compromise patients' functional capacity and QoL [33]. Similar associations between the symptomatology and functional scales were also observed in the control group, indicating that the above-mentioned clinical symptoms influence the individuals' daily life independently of the disease.

Moreover, with regard to the relationship between exercise behavior and QoL, a positive correlation was found between participation in vigorous PAs and QoL, as well as between total energy expenditure and physical functioning in women with BCa. These findings corroborate a large body of evidence supporting the hypothesis that a greater energy expenditure during the week leads to a better functional ability, while participation in more intense activities implies a better self-evaluated QoL [34,35]. Moreover, the strong positive correlations found between physical, social and emotional functioning further support previous findings that mental health symptoms and isolation are followed by a poor functional ability in cancer patients [36,37].

Putting all the above findings together, it appears that new approaches are urgently needed to improve tolerance and reduce the adverse e ffects of chemotherapy in cancer patients [38]. Physical activity interventions should be incorporated in cancer non-pharmaceutical treatments during chemotherapy, since the worst side e ffects of cancer therapy are experienced during this period, while exercise can mitigate unfavorable changes in various physiological systems and their consequent symptoms [39–41]. Clinical physicians are proposed to assess, advise and refer cancer patients to exercise [19,42,43].

#### **5. Conclusions and Future Perspectives**

The outcomes of the present study unveil a close relationship between exercise behavior and QoL in breast cancer patients; however, there remain challenging issues to be further addressed. Future research lines of investigation should focus on the dose-dependent e ffects of physical activity and on revealing the optimum dose as well as the potential maximum and minimum thresholds of the cancer patients for benefit from physical activity. Furthermore, it remains a challenge to elucidate whether cancer type, timing of physical activity and its specific components influence the e ffectiveness of exercise and its interactions with cancer outcomes. For instance, in order for vigorous physical activities to be realistically adopted and sustained by those patients during their treatment, a mode of short-duration high-intensity physical exercise with adequate breaks might be a more applicable suggestion for them, so as to take advantage of the time-e ffective, beneficial e ffects of vigorous activities on their quality of life and physical functioning. Since physical activity is an important factor for cancer prevention and treatment, policy makers, public health professionals, health care providers, and exercise scientists should all communicate and promote the benefits of physical activity for both cancer prevention and control, and work together with other stakeholders to improve the health and quality of life of cancer patients.

**Author Contributions:** Conceptualization: M.M., A.P. (Argyro Papadopetraki), H.K., A.P. (Anastassios Philippou); methodology: M.M. and A.P. (Anastassios Philippou); investigation: H.K., A.P. (Argyro Papadopetraki); data curation: A.P. (Argyro Papadopetraki), H.K; writing—original draft preparation: A.P. (Argyro Papadopetraki); writing—review and editing: M.M., A.P. (Anastassios Philippou), M.K.; supervision: M.M., A.P. (Anastassios Philippou). All authors have read and agreed to the published version of the manuscript.

**Funding:** This research received no external funding.

**Acknowledgments:** The authors are grateful to the study participants for their invaluable contribution to this study.

**Conflicts of Interest:** The authors declare no conflict of interest.
