Background Breast cancer (BC) surveillance primarily aims to detect locoregional recurrence (LRR) and contralateral breast cancer (CBC), but current strategies are largely one-size-fits-all and not tailored to individual risks. The Dutch INFLUENCE 3.0 prediction model provides personalised 5-year LRR and CBC risks to support shared decision-making on surveillance. In this study, INFLUENCE 3.0 is externally validated in a Belgian population. Methods All female BC patients curatively treated between 2000 and 2018 at the University Hospitals of Leuven were included. Calibration was assessed using the Integrated Calibration Index (ICI), E50, E90 metrics, and calibration plots. Discrimination was evaluated by calculating the Area Under the Curve (AUC) for each year, based on cumulative events up to that year. Results The final Leuven cohort included 8548 patients, of whom 7549 were not treated with neoadjuvant systemic therapy (non-NST) and 999 were (NST). Calibration metrics were generally acceptable, with ICI and E50 values below 0.01 in most subgroups. Calibration plots showed overestimation of predicted risks, particularly at lower predicted risk levels. Discrimination for LRR risk was good to very good (AUC 0.72–0.86 in the non-NST group; >0.82 in the NST group). For CBC risk, discrimination was poor in the non-NST group (AUC ≈ 0.5) and moderate-to-very good in the NST group (AUC 0.68–0.88). Conclusion INFLUENCE 3.0 showed acceptable calibration and discrimination for LRR risk, and although CBC risk discrimination in the non-NST group was poor. The overall risk estimates – primarily the LRR risks – may still help in guiding tailored surveillance schemes.
Background Growing evidence has shown that Mind-Body Transformations-Therapies (MBT-T) are able to modulate chronic inflammation, a well-known driver of cancer progression and drug resistance. In our previous work, we showed that a specific MBT-T protocol was able to reduce the release of various pro-inflammatory cytokines and chemokines in the sera of patients with breast cancer that completed adjuvant chemotherapy. Despite these clinical observations, the underlying molecular pathways through which this therapy exerts its effects remain unclear. This study aims to address this gap by characterizing genome-wide transcriptional profiles in patients undergoing a novel MBT-T protocol. Methods In this proof-of-concept study, patients with breast cancer were randomized into two groups: Group 1 (CTL), receiving standard follow-up care, and Group 2 (MBT-T), receiving standard follow-up plus biweekly MBT-T for 4 months. Blood samples were collected at different timepoints during the treatment. After RNA extraction from whole blood, gene expression was analyzed on twenty-one patients (CTL, n=7; MBT-T, n=14) using the nCounter® Human Inflammation Panel (249 genes). Results Patients undergoing MBT-T showed a significant global downregulation of inflammatory gene expression compared to the control group. The analysis revealed that the Interferon (IFN) signaling pathway was the most significantly suppressed, by downregulation of key genes such as IFIT1, IFIT3, IFI44, MX1 and OASL in the MBT-T group. Conclusions MBT-T acts as a biological modulator capable of downregulating key inflammatory pathways at the transcriptional level. These findings provide a genomic basis for the clinical benefits of mind-body interventions in oncology.
Introduction Circulating thymidine kinase 1 activity (TKa) is a potential prognostic biomarker in patients with hormone receptor-positive (HR+) metastatic breast cancer (MBC); however, results are heterogeneous. In this study we aimed to summarize the current evidence on the prognostic role of circulating TKa in women with HR+ MBC. Methods We conducted a systematic review of PubMed, Embase, and Cochrane CENTRAL databases and abstracts from main international oncology meetings. Phase II-IV clinical trials and prospective observational studies in patients with MBC assessing circulating TK1 levels or TKa and reporting hazard ratios (HRs) for progression-free survival (PFS) and/or overall survival (OS) were included. HRs were pooled using random-effects models (restricted maximum likelihood with Hartung-Knapp adjustment), with heterogeneity quantified by I2 and prediction intervals. The primary study outcome was the association of baseline and on-treatment TKa with PFS and OS. Secondary analyses aimed at exploring the source of heterogeneity. Results Eighteen studies, reporting data from nearly 3000 women, were included in the systematic review and 15 studies were meta-analyzed. Patients with HR+ MBC and high baseline TKa showed a significantly higher risk of progression (PFS: HR 1.90; 95% CI 1.57–2.30; p < 0.001) and death (OS: HR 2.48; 95% CI 1.94–3.17; p < 0.001) than those with low TKa. TKa at 2 and 4 weeks on-treatment was also prognostic (2 weeks, PFS: HR 2.76; 95% CI 2.34–3.26; p < 0.001; 4 weeks, HR 2.26; 95% CI 1.93–2.66; p < 0.001). Similar pooled effects were obtained when accounting for different cut-offs, TKa assessment, and sample-type. Conclusion Pre-treatment high TKa is an adverse prognostic factor in women with HR+ MBC. High on-treatment TKa is also associated with worse outcome, potentially serving as an early signal of treatment resistance. We provide a comprehensive summary of the currently available evidence on the prognostic value of circulating TKa.
BACKGROUND:Metastatic breast cancer (MBC) remains a treatable, but incurable disease. Anti-cancer treatments and supportive therapies aim to control disease, prolong survival, ameliorate physical symptoms and improve quality of life (QoL). Currently, no validated MBC-specific patient-reported outcome measures exist, and existing tools may lack specific content and sensitivity to measure the impact of MBC. This study aims to develop a European Organisation for Research and Treatment of Cancer (EORTC) module for MBC. METHODS:Development followed EORTC module guidelines. In phase 1, QoL issues were identified via systematic literature reviews and assessed by semi-structured interviews with healthcare professionals (HCPs) and patients. In phase 2, the most relevant and important issues were converted into questionnaire items using the EORTC Item Library to form the provisional module. RESULTS:The review included 103 papers (phase III clinical trials n = 70 and observational or qualitative studies n = 33), from which 185 issues were extracted, spanning physical, psychological, emotional and social domains. Interviews with 41 HCPs and 187 patients from eight countries refined this list to 44. After expert panel review, the provisional module consisted of 40 issues, assessed by 44 items (EORTC QLQ-MBR44). A sub-analysis of the EORTC QLQ-C30 revealed its content to be considered relevant to MBC by HCP and patients. CONCLUSION:The provisional EORTC MBC-specific module aims to enhance understanding and measurement of QoL in clinical research and care and be the first QoL tool dedicated to MBC. The standardised tool contains relevant QoL issues and is currently undergoing qualitative and psychometric testing.
