Background: Quality of life issues is a crucial burden in breast cancer (BC) survivors with relevant implications in terms of survivorship and health-care costs. The increasing long-term survival of these patients provides new challenges, with translational research now focusing on innovative and tailored approaches to improve their complex management. In this scenario, several emerging biomarkers have the potential to improve the clinical rehabilitative management of patients with BC. However, to date, guidelines supporting biomarker implementation in this area are still lacking. Therefore, the aim of this systematic review was to summarize the currently available biomarkers that might be potentially integrated into rehabilitation practice to promote a precision medicine approach to BC survivorship issues.Methods: On 9th March 2022, PubMed, Scopus, Web of Science, Cochrane, and PEDro were systematically searched for randomized controlled trials (RCTs) assessing rehabilitation interventions in BC patients. Molecular biomarker modifications induced by physical exercise have been assessed through the review of the study protocols and published results. The Jadad scale was used to assess the quality of the studies included.Results: Out of 2,224 records, 22 studies were included in the present systematic review. Exercise therapy showed significant results in 15 RCTs, in terms of metabolic biomarkers, including glycemic and insulin profile, and lipid profile (p ≤ 0.05). Similarly, 12 studies underlined significant effects in inflammation and immune response biomarkers, including TNF-α, IL-6, IL-10, C-reactive protein, leptin, and adiponectin (p ≤ 0.05). On the other hand, cardiac biomarkers were assessed in three studies without reporting significant differences after exercise therapy (p = NS). The quality assessment identified 19 RCTs as high-quality studies and three RCTs of low quality.Conclusion: Our findings reveal significant biochemical perturbations in key molecules induced by physical exercise in patients with BC, suggesting room for the implementation of actionable biomarkers. Future research might clarify the role of biomarkers on treatment effectiveness monitoring, to optimize rehabilitative strategies tailored to patient’s needs.

Introduction. Triple-negative breast cancer (TNBC) accounts for most breast cancer-related deaths due to its aggressiveness and lack of effective therapies. Chimeric antigen receptor (CAR)-T cells emerged as a promising immunotherapeutic strategy both in TNBC preclinical models and earlyphase clinical trials. These drugs combine the antigen specificity of an antibody with the effector function of T cells. Areas covered.Here, we present the challenges that hamper the safety and efficacy of CAR-T cells in solid tumors, along with the most studied targets in TNBC.Expert Opinion. A relevant challenge in the development of CAR-T cells for TNBC is the selection of the optimal target to minimize on-target/off-tumor toxicity, as well as to reduce tumor escape via antigen loss and intrinsic heterogeneity. To date, TROP2, GD2, ROR1, MUC1 and EpCAM represent promising targets. Persistence and trafficking to tumor cells may be enhanced by the implementation of CARs with a chemokine receptor and/or constitutively activated interleukin receptors. Fourthgeneration CARs (TRUCKs) may redirect T-cells for universal cytokine-mediated killing. Finally, combinatorial approaches and the application of CARs to other immune cells might revert the suppressive immune environment that characterizes solid neoplasms.

Background: Axillary web syndrome (AWS) is one of the most prevalent and underrecognized disorders affecting breast cancer (BC) women. However, the optimal therapeutic strategy to manage AWS is far from being fully characterized. Therefore, this systematic review aims to provide a broad overview of the available rehabilitation treatments in this burdensome condition. Methods: On 13 January 2022, PubMed, Scopus, Web of Science, Cochrane, and PEDro were systematically searched for clinical studies assessing rehabilitation interventions in post-surgical BC women with AWS. The outcomes analyzed were pain, AWS clinical resolution, upper limb function, and health-related quality of life (HR-QoL). Results: The search identified 1115 records, of which 11 studies were included. A total of 174 patients were assessed (ages ranging from 37 and 66 years old). The interventions included manual lymphatic drainage, manual therapy, stretching, resistance training, mobilization techniques, and Kinesio tape. Positive improvements were reported in terms of pain relief (in 7 studies), AWS clinical resolution (in 9 studies), upper limb function (in 10 studies), and HR-QoL (in 2 studies). Conclusions: Our findings suggest that rehabilitation might be considered an effective therapeutic strategy in AWS patients. Further RCTs are needed to characterize the optimal rehabilitative interventions.