Introduction: Exergames have been successfully utilized in healthcare, namelyin rehabilitation care. The present paper, authored by individuals who are aware of the potential of this technological resource, is intended to contribute to the construction of a rehabilitation nursing program that incorporates exergames for patients that have undergone breast cancer surgery. Methodology: We conducted a Scoping review study. The research was performed in the following databases; MEDLINE® (Medical Literature Analysis and Retrieval System Online), CINAHL® (Cumulative Index to Nursing and Allied Health Literature), SPORTDiscus, SCOPUS,SciELO (Scientific Electronic Library Online), Psychology and Behavioral Sciences Collection, Cochrane Central Register of Controlled Trials e PEDRo (PhysiotherapyEvidence Database) identifying all studies published by January 31, 2022, accordingwith Joanna Briggs Institute´s and PRISMA-ScR´s guidelines. Results: Thirteenarticles, published between 2015 and 2021, were selected. In total, there were 441participants. Platforms, such as Xbox and Nintendo Wii, that are compatible withgames that involve motion, were the most used. The duration of the interventionstrategies ranged from 15 days to 12 weeks. The majority of the interventions occurred in the late postoperative recovery phase. Intervention with exergames generated superior or similar results to traditional rehabilitation in terms of pain, upper limb functionality, range of motion, fatigue and quality of life. Conclusion: The present Scoping review emphasises the positive impact of the use of exergames in the rehabilitation of individuals with breast cancer. However, it is pertinent to conduct a greater number of scientific studies in this area that allow determining the type of game, time and frequency of intervention that optimize the level of effectiveness.   keywords: Breast Neoplasms; Exergames, Rehabilitation

Oncologic disease is an aversive context, stressor, to which the person responds in the attempt to repair the troubled relation between herself and the environment, triggering a process of adaptation. The monitoring of the adaptation of patients along the health/illness transition, using indicators sensitive to nursing care, will enhance the design of effective and efficient nursing therapeutics, with repercussions on care improvement. We went for the construction of a measuring instrument due to lack a scale that assesses the construct adaptation, focused on the results. Objective: To describe the second part of the construction of a measuring instrument that aims to evaluate the adaptation of women to breast cancer and that is sensitive to nursing care process. Methodology: Approach: exploratory, qualitative and quantitative. The building process took place over six stages, five of which have been described in a previous article: literature review; interviews with people with breast cancer who belong to a self-help group, selection of outcome indicators sensitive to nursing care, as described in the NOC; critical reading of the connections of the NANDA and NOC classifications; analysis by the expert panel. This article describes the sixth stage of construction of the measuring instrument that includes conducting a survey on the National Institutes of Oncology. Results: The results of this study culminated in a scale called “Instrument for monitoring the adaptation of women to breast cancer,” which consists of 35 outcome indicators. Discussion: In the process of construction of the scale it is evident the multidimensionality of the construct “adaptation”. Based on NOC, it is found that the measuring instrument aggregates 18 fields which unfold into 35 items that correspond to the outcome indicators sensitive to nursing care. Conclusion: We describe the last part of the construction of a measuring instrument that aims to evaluate the result of the adaptation of women to breast cancer, and that ensures its content validity process. The instrument can be a contribution to clinical utility, enabling nurses to monitor the result of their interventions towards a healthy transition.

This article describes the initial process of identifying a set of outcome indicators, clinically useful, which would enhance the monitoring of the adaptation processes in patients with breast cancer. The breast oncology disease is a powerful agent of stress that could threaten the psychological and physical integrity of the person, representing a violent impact on the well-being and quality of life. In the methodology we used, a qualitative exploratory approach, using literature review, expert evaluation and exploratory interviews with patients with breast cancer, which belong to a self-help group, was performed. In a first approach, according to the literature review, we can infer that a more active coping style in the form of fighting spirit, social support, self-control, favorable rates of optimism and spiritual dimension present induces patterns of more adaptive responses. From the results of the exploratory interviews and the literature review, we have evolved to identify a very broad set of performance indicators in nursing, using the Nursing Outcomes Classification. These set of indicators was submitted to a panel of experts in this problematic area. According to the experts’ choices, we were able to reach a panel of 110 outcome indicators, potentially useful for monitoring and following of patients who experience a situation of breast cancer disease. We conclude that it is fundamental to the nursing discipline to identify outcome indicators, useful, measurable, and to assess the health care as a mean of sustaining the quality of nursing practice.

Cardiotoxicity 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.

Breast cancer remains the oncological disease with the greatest impact on morbidity and mortality in women worldwide. Prolonged exposure to estrogens is considered one of the main risk factors for breast cancer. This carcinogenic process is potentiated by genetic alterations in lowpenetrance genes in the estrogen biosynthetic and metabolic pathways. Phase II enzymes responsible for estrogens detoxification, are regulated by the NRF2- KEAP1 (nuclear factor erythroid 2-related factor 2 - kelch-like ECH-associated protein 1) complex. The value of this complex in estrogen detoxification led us to the aim of this thesis, which is to validate the NRF2-KEAP1 complex as a marker for breast cancer prognosis and therapy. Thus, we studied the influence of genetic polymorphisms, in low penetrance genes of the estrogen metabolic pathway in breast cancer development. The genotype of Val432Leu, C677T and null polymorphisms, respectively of CYP1B1, MTHFR, GSTM1 and GSTT1 genes, were assessed in women with hormone-dependent breast cancer. It was verified that carriers of the null genotype of GSTT1, alone or in association with the null genotype of GSTM1, as well as carriers of Val432 of CYP1B1 and the null polymorphism of GSTT1 or GSTM1, and carriers of the null genotype of GSTT1 and the T allele of the C677T polymorphism, were diagnosed with breast cancer at the age of 50 or over. The results indicate that polymorphisms that contribute to inefficient estrogen detoxification may predispose women to developing hormone-dependent breast cancer at a later age. In order to assess the clinical influence of the NRF2 rs35652124, rs6706649, rs6721961 polymorphisms and the KEAP1 rs1048290 polymorphism in breast cancer cases with a "present" GSTM1 genotype, a technique was optimised which made it possible to distinguish heterozygous from present genotypes. Heterozygous GSTM1 cases cumulatively carriers of the NRF2 and/or KEAP1 polymorphisms were associated with HER2+ (epidermal growth factor receptor 2 positive) breast cancers. There are several studies correlating NRF2 polymorphisms and its expression with breast cancer prognosis. After a systematic review with meta-analysis, it was found that patients with NRF2 over-expression had lower overall survival and shorter disease-free survival. Subsequently, the genotypes of the aforementioned KEAP1 and NRF2 polymorphisms were assessed in blood, tumour’s benign surrounding tissue and tumour tissue. There was a trend towards the loss of heterozygosity in the benign surrounding tissue and a greater variability of genotypes in histological grade 2. The acquisition of somatic mutations and their different distribution are probably the result of a more active and heterogeneous microenvironment. Polymorphisms that compromise the availability of NRF2 in the nucleus impair estrogen detoxification and may predispose to the development of postmenopausal breast cancer. High levels of NRF2 in the nucleus promote high detoxification, protecting both healthy and tumour cells. It is therefore pertinent to carry out further studies in benign and tumour tissue, in different subgroups of participants, in order to understand the role of the complex in the development and progression of breast cancer.

Photothermal therapy has emerged as a new promising strategy for the management of cancer, either alone or combined with other therapeutics, such as chemotherapy. The use of nanoparticles for multimodal therapy can improve treatment performance and reduce drug doses and associated side effects. Here we propose the development of a novel multifunctional nanosystem based on solid lipid nanoparticles co-loaded with gold nanorods and mitoxantrone and functionalized with folic acid for dual photothermal therapy and chemotherapy of breast cancer. Nanoparticles were produced using an economically affordable method and presented suitable physicochemical properties for tumor passive accumulation. Upon Near-Infrared irradiation (808 nm, 1.7 W cm -2, 5 min), nanoparticles could effectively mediate a temperature increase of >20 ◦C. Moreover, exposure to light resulted in an enhanced release of Mitoxantrone. Furthermore, nanoparticles were non-hemolytic and well tolerated by healthy cells even at high concentrations. The active targeting strategy was found to be successful, as shown by the greater accumulation of the functionalized nanoparticles in MCF-7 cells. Finally, the combined effects of chemotherapy, light-induced drug release and photothermal therapy significantly enhanced breast cancer cell death. Overall, these results demonstrate that the developed lipid nanosystem is an efficient vehicle for breast cancer multimodal therapy.

Anthracyclines 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.

Breast cancer is the leading cause of cancer-related deaths among women worldwide. The conventional chemotherapeutic regimens used in the treatment of this disease often lead to severe side-effects and reduced efficacy. In this study, a novel drug delivery system for the chemotherapeutic drug mitoxantrone (Mito) was developed using solid lipid nanoparticles (SLN). The production of the SLN was carried out using an organic-solvent-free, low-cost method and optimized using a Box-Behnken design. SLN presented adequate size for cancer-related applications, more than 90% of EE% and remained stable for at least 6 months. A much higher drug release was obtained at acidic pH (mimicking the endosomal compartment) than plasmatic pH, highlighting the potential of the nanosystem for tumor drug delivery. Additionally, SLN were non-hemolytic and cytocompatible, even at high concentrations of lipid. A significantly higher anti-cancer efficacy was obtained for Mito-loaded SLN comparing to the free drug at different concentrations in MCF-7 2D models. Finally, the nanoformulation was evaluated in heterotypic breast cancer spheroids showing capacity to penetrate the tridimensional structure and ability to induce a high anti-tumoral effect, similarly to the free drug. Overall, these results support that the developed SLN are effective Mito nanocarriers for the treatment of breast cancer.

Aim: To evaluate the therapeutic capacity of D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS)-functionalized nanographene oxide (nGO) in breast cancer cells. Methods: TPGS-functionalized nGO-based materials were obtained through two different approaches: a simple sonication method and a one-pot hydrothermal treatment. Results: TPGS coating successfully improved the stability of the nGO-based materials. The nanomaterials that underwent the hydrothermal procedure generated a 1.4- to 1.6-fold higher temperature variation under near infrared laser irradiation than those prepared only by sonication. In vitro, the TPGS/nGO derivatives reduced breast cancer cells’ viability and had an insignificant effect on healthy cells. Furthermore, the combined application of TPGS/nGO derivatives and near infrared light generated an improved therapeutic effect. Conclusion: TPGS/nGO derivatives are promising materials for breast cancer phototherapy.

Breast cancer is among the foremost causes of mortality on a global scale, exemplifying the disease's resilience and adaptability. The conventional clinical approaches, notably encompassing surgery, radiotherapy, chemotherapy, and immunotherapy, present significant limitations: subpar efficacy and adverse events/side effects. In view of these challenges, it is crucial to develop innovative strategies that can contribute for reducing the mortality rates related to breast cancer. In recent years, strategies based on nanomaterials for chemo-photothermal therapy have started to light the path, showcasing promising results in cancer treatment. The unique physical and chemical properties of these nanomaterials enable the encapsulation of chemotherapeutic drugs as well as their journey into the tumor site. In turn, the optical features enable these nanomaterials to absorb light in the near-infrared (NIR) region, deploying a localized heat. The combined action of these two modalities (drug delivery and photoinduced heat) amplifies the destruction of cancer cells. However, the limited capacity of nanomaterials to reach the tumors, following systemic administration, continues to represent a significant impediment to its full therapeutic capacity. The pursuit for overcoming the systemic administration problems has led to the development of injectable in situ forming hydrogels. These injectable hydrogels have the capacity to encapsulate anticancer agents (including drugs and nanomaterials), and to deliver them locally into the tumors. Among these, injectable hydrogels formed in situ by chemical crosslinking have gained popularity due to their stability and greater control over structural and functional properties (e.g., degradation rate, swelling capacity). In particular, injectable in situ forming hydrogels crosslinked by Thiol-Maleimide reaction are emerging due to the advantageous features of this chemistry: chemo-selectivity and rapid kinetics. In this MSc dissertation, a chemically crosslinked injectable in situ forming hydrogel was developed based on the Thiol-Maleimide reaction between thiolated poly(acrylic acid) and 4-arm poly(ethylene glycol)-maleimide. This hydrogel was incorporated with dopamine-reduced graphene oxide (DOPA-rGO; nanosized photothermal agent) and Doxorubicin (DOX; chemotherapeutic drug), being exploited for the chemo-photothermal therapy of breast cancer. The assembled formulations exhibited injectability and capacity to gelate in situ through the Thiol-Maleimide reaction. The degradation studies highlighted the excellent integrity of the hydrogels. Furthermore, the incorporation of DOPA-rGO into the hydrogel enabled the attainment of a minimal and well-controlled swelling. As importantly, the inclusion of DOPA-rGO into the hydrogel allowed a high photothermal effect under NIR irradiation, that also enhanced the release of DOX by up to 1.5-times. In vitro tests displayed the hydrogels’ favorable cytocompatibility. Besides this, the hydrogels incorporating both DOPA-rGO and DOX generated an effect under NIR irradiation that reduced the breast cancer cells’ viability to just ≈25%, hence confirming their chemo-photothermal capacity. In summary, the injectable hydrogels developed in this dissertation, based on the Thiol-Maleimide reaction between thiolated poly(acrylic acid) and 4-arm poly(ethylene glycol)-maleimide, that incorporated DOPA-rGO and DOX, have showcased auspicious results for application in the chemo-phototherapy of breast cancer cells.