Diathermy techniques embody an oscillating electrical current passaging through the body tissues generating therapeutic heat; use of this technique in the physiotherapy field has been introduced recently, and because there is scarce information, the following review is proposed, aiming to explore the available evidence on applying CRET in physiotherapy clinical practice and sports. A systematic search was led through a keyword search on PubMed, MedLine, DialNet, Scopus, PEDro, Web of Science and Clinicaltrials databases. Including randomised controlled trials and quasi-experimental studies, which applied radiofrequency diathermy in sports and physiotherapy fields, without any restrictions on dates, published in Spanish, English, Portuguese or Italian. Data extraction was conducted through the Cochrane data extraction form and presented in tabular format; 30 articles were included for analysis, and assessment of methodological quality was made through the PEDro scale with a “Good/Fair” general quality score. The nature of existing articles does not allow a quantitative analysis. Conclusion: identified fields of applications were musculoskeletal physiotherapy, treatment of pelvic floor and sexual dysfunctions, as well as dermato-functional physiotherapy and sports, evidencing an increase of skin temperature, enhanced skin and muscle blood perfusion, as well as reporting an increase in oxyhaemoglobin. Further research is needed. Prospero registration number: CRD42020215592.

Purpose: Tumor progression has been linked to stiffening of the extracellular matrix caused by fibrosis. Cancer cells can be mechanically conditioned by stiff extracellular matrix, exhibiting a 1,004-gene signature [mechanical conditioning (MeCo) score]. Nintedanib has demonstrated antifibrotic activity in idiopathic pulmonary fibrosis. This study explores nintedanib’s antifibrotic effect on breast cancer outcomes. Experimental Design: We present long-term follow-up and analysis of a neoadjuvant randomized phase II trial in early HER2-negative breast cancer. Patients (N = 130) underwent a baseline biopsy and received 12 paclitaxel courses alone (control arm) or in combination with nintedanib (experimental arm). The tumor MeCo score was determined by RNA sequencing. The primary aim was to assess nintedanib’s impact on event-free survival based on MeCo scores. Results: Follow-up data were retrieved from 111 patients; 75 baseline and 24 post-run-in phase samples were sequenced. After median follow-up of 9.67 years, median event-free survival was not statistically different between arms (P = 0.37). However, in the control arm, high- versus low-MeCo patients had a statistically higher relapse risk: HR = 0.21; P = 0.0075. This risk was corrected by nintedanib in the experimental arm: HR = 0.37; P = 0.16. Nintedanib demonstrated pharmacodynamic engagement, reducing the MeCo score by 25% during the run-in phase (P < 0.01). Patients with low MeCo after run-in had the best long-term prognosis (HR = 0.087; P = 0.03). Conclusions: High MeCo is predictive of poor outcomes in HER2-negative early breast cancer, although this risk can be mitigated by nintedanib, which is able to specifically reduce MeCo.

Purpose: HER2DX is a validated genomic assay used to support treatment decisions in early-stage HER2-positive (HER2+) breast cancer. It provides three scores: relapse risk, likelihood of pathologic complete response (pCR), and ERBB2 mRNA expression. This study aimed to evaluate the association between HER2DX and histopathologic features and assess its relationship with pCR after neoadjuvant therapy. Experimental Design: Patients with newly diagnosed stage I to III HER2+ breast cancer were analyzed based on available HER2DX results during routine care in Spain (January 2022–June 2025). Centralized HER2DX testing was performed on formalin-fixed, paraffin-embedded tumor samples. Histopathologic analysis included tumor grade, hormone receptor status, histologic subtype, Ki67 index, HER2 IHC score, stromal tumor-infiltrating lymphocytes (TIL), tertiary lymphoid structures, and spatial immune distribution. Univariate and multivariable logistic regression analyses were conducted to identify factors associated with pCR after neoadjuvant trastuzumab-based therapy. Results: A total of 410 HER2+ tumors were analyzed, and 250 patients received neoadjuvant trastuzumab-based therapy with available surgical outcomes (36% achieved a pCR). HER2DX pCR scores were significantly associated with all eight histopathologic features, whereas relapse risk and ERBB2 scores were associated with five and two, respectively. TIL correlated with the immune/immunoglobulin signature (r = 0.59), and Ki67 with the proliferation signature (r = 0.50). The HER2DX pCR score remained the only independent predictor of pCR in multivariable analysis (OR, 1.77; 95% confidence interval, 1.08–2.97; P = 0.030). Conclusions: HER2DX reflects key biological and pathologic features of HER2+ breast cancer and independently predicts pCR, supporting its utility for individualized treatment decision-making.

Associations between HER2DX scores and histopathologic variables.

Associations between HER2DX pCR score and standard pathologic features. Distribution of HER2DX pCR score groups (low, medium, and high; A); HER2DX pCR score by tumor grade (B), HR status (C), HER2 IHC status (D), TLS status (E), and spatial immune distribution (F). All scores are shown on a continuous scale from 1 to 99. Boxplots show IQR with medians indicated and display score distributions across groups. Statistical comparisons were performed using appropriate parametric tests.

Purpose:HER2DX is a validated genomic assay used to support treatment decisions in early-stage HER2-positive (HER2+) breast cancer. It provides three scores: relapse risk, likelihood of pathologic complete response (pCR), and ERBB2 mRNA expression. This study aimed to evaluate the association between HER2DX and histopathologic features and assess its relationship with pCR after neoadjuvant therapy.Experimental Design:Patients with newly diagnosed stage I to III HER2+ breast cancer were analyzed based on available HER2DX results during routine care in Spain (January 2022–June 2025). Centralized HER2DX testing was performed on formalin-fixed, paraffin-embedded tumor samples. Histopathologic analysis included tumor grade, hormone receptor status, histologic subtype, Ki67 index, HER2 IHC score, stromal tumor-infiltrating lymphocytes (TIL), tertiary lymphoid structures, and spatial immune distribution. Univariate and multivariable logistic regression analyses were conducted to identify factors associated with pCR after neoadjuvant trastuzumab-based therapy.Results:A total of 410 HER2+ tumors were analyzed, and 250 patients received neoadjuvant trastuzumab-based therapy with available surgical outcomes (36% achieved a pCR). HER2DX pCR scores were significantly associated with all eight histopathologic features, whereas relapse risk and ERBB2 scores were associated with five and two, respectively. TIL correlated with the immune/immunoglobulin signature (r = 0.59), and Ki67 with the proliferation signature (r = 0.50). The HER2DX pCR score remained the only independent predictor of pCR in multivariable analysis (OR, 1.77; 95% confidence interval, 1.08–2.97; P = 0.030).Conclusions:HER2DX reflects key biological and pathologic features of HER2+ breast cancer and independently predicts pCR, supporting its utility for individualized treatment decision-making.