Search Results (304)

Background/Objectives: Breast/chest wall (B/CW) re-irradiation (reRT) is approached cautiously because of concerns regarding late toxicity and uncertain benefit. Contemporary data on mature toxicity and oncologic outcomes after external beam photon reRT are limited. Methods: This retrospective cohort included 113 consecutive patients who completed reRT after resection of locoregionally recurrent breast cancer between 2010 and 2024. The primary endpoint was cumulative incidence of late grade ≥ 2 CTCAE toxicity, analyzed using competing-risks methods. Secondary endpoints were locoregional recurrence-free survival (LRRFS) and local failure (LF), assessed using Kaplan–Meier, Cox regression, and Fine–Gray modeling. Results: Median age at reRT was 66 years. Most recurrences were early-stage (72.6%) and hormone receptor-positive (68.1%). Median cumulative EQD2 was 94.9 Gy, and 25.7% received IMRT. At 67.1 months’ median follow-up, 5-year cumulative incidences of grade ≥ 2 and grade 3 toxicity were 35.4% (95% CI, 25.6–45.1) and 3.9% (95% CI, 0.1–7.8), respectively. Higher cumulative EQD2 predicted grade ≥ 2 toxicity (SHR, 1.94 per 10 Gy; p < 0.001) and grade 3 toxicity (SHR, 4.32 per 10 Gy; p < 0.001). Longer interval between radiotherapy courses (p = 0.029) and IMRT (SHR, 0.40; p = 0.005) were associated with lower grade ≥ 2 toxicity. Five-year LRRFS was 84.2% (95% CI, 76.7–92.4), and LF was 6.8%. Advanced-stage disease and second or subsequent recurrence predicted inferior LRRFS. Partial B/CW reRT did not compromise disease control in early-stage recurrences. Conclusions: Adjuvant breast and chest wall re-irradiation using external photons achieved durable locoregional control with low rates of severe late toxicity in one of the largest reported cohorts. These findings support individualized curative-intent reRT guided by cumulative dose, technique, and recurrence risk. Full article

Neoadjuvant chemotherapy (NAC) is the standard of care for locally advanced breast cancer, yet the molecular predictors of pathological response remain incompletely defined, particularly regarding microRNA (miRNA) dynamics. We investigated paired pre- and post-NAC miRNA expression profiles in relation to molecular subtype, residual cancer burden (RCB), and clinical timing parameters. Seven patients with invasive breast cancer (Luminal A n = 3, Luminal B n = 1, TNBC n = 2, HER2+ n = 1) who received NAC (AC-T or TCHP) were included in this pilot study. Small-RNA sequencing (NovaSeq X Plus, CeGaT GmbH, project S17293) was performed on 14 FFPE specimens (7 pre-NAC core needle biopsies, 7 post-NAC surgical specimens). Differential expression analysis used the paired Wilcoxon signed-rank test with Benjamini–Hochberg correction. Spearman correlations assessed associations between miRNA expression, RCB score, and clinical timing intervals. Candidate miRNAs were subsequently annotated using experimentally validated miRNA–target interactions. After filtering (≥ three counts in ≥ three samples), 759 miRNAs were analysed. No miRNA reached strict significance (padj < 0.05, |log₂FC| > 1.0) after multiple testing correction, consistent with the limited statistical power (n = 7). Under exploratory criteria (p < 0.10, |log₂FC| > 0.5), 156 candidate miRNAs were identified: 70 upregulated and 86 downregulated post-NAC. Leading candidates included hsa-miR-139-3p (+2.60), hsa-miR-139-5p (+2.36), and hsa-miR-1323 (+1.55) as upregulated, and hsa-miR-429 (−2.53), hsa-miR-141-3p (−1.79), and hsa-miR-1277-5p (−1.25) as downregulated post-NAC. The single patient achieving the lowest residual disease burden (P3, Luminal B, RCB-I, score 1.32) displayed a distinct pre-treatment miRNA profile, separating from all other pre-NAC specimens on principal component analysis and characterised by higher baseline hsa-miR-139-3p/-5p and lower baseline hsa-miR-429 and hsa-miR-141-3p expression, suggesting that baseline miRNA expression patterns may contribute to differential chemotherapy response. RCB score showed a non-significant positive trend with post-NAC Ki-67 (ρ = +0.71, p = 0.07). This pilot study identifies NAC-modulated candidate miRNAs in breast cancer and establishes a paired FFPE-based small-RNA-sequencing workflow applicable in routine clinical settings. The distinct pre-treatment profile of the single best responder generates the testable hypothesis that baseline expression of tumour suppressor miRNAs of the miR-139 family, together with low miR-200-family expression, may track chemosensitivity. As no candidate reached statistical significance after multiple testing correction and none has been validated in an independent cohort or by an orthogonal method, all findings are exploratory and hypothesis-generating. The results support larger prospective validation studies examining miRNA signatures as predictive biomarkers of NAC response across breast cancer molecular subtypes. Full article

Cancer remains one of the leading causes of death globally, and breast cancer is the most frequently diagnosed cancer in women. Even though surgical excision is the main treatment of solid tumors, recurrence and metastasis to another location postoperatively provide lasting therapeutic challenges. Systemic adverse effects and a lack of sufficient drug bioavailability at the resection site can often hinder traditional adjuvant modalities, especially chemotherapy and radiotherapy. To address these drawbacks, localized drug delivery platforms have gained a lot of interest, and hydrogels have emerged as highly beneficial systems. Hydrogels are three-dimensional hydrophilic polymer networks that can be designed to be injectable and in situ-forming. They can be engineered to fit irregular surgical cavities and deliver therapeutics in a long-lasting, controlled manner. The current literature review outlines the clinical issue of tumor recurrence following surgery with a special focus on breast cancer and evaluates hydrogel-based methods of site-specific therapy. We outline the categorization, assembly, and functionalization of hydrogel systems based on natural, synthetic, and hybrid polymers, and reflect on advanced stimuli-responsive and cell-targeted formulations in the context of cancer immunotherapy. This paper presents the translational applications of hydrogel platforms to enhance postoperative management and prevent tumor recurrence by combining new advances. Full article

Interleukin-12 (IL-12) potently promotes the recruitment and activation of immune cells within the tumor microenvironment (TME), highlighting its immense potential for cancer therapy. However, its dose-limiting systemic toxicity and short half-life severely hinder its clinical translation. Here, we design a tumor-conditionally activated IL-12 prodrug termed αHSA-proIL-12. This engineered molecule integrates a cleavable albumin-binding nanobody (αHSA) domain to extend the half-life and enhance tumor targeting alongside a masking domain that occludes the IL-12 receptor-binding site to prevent nonspecific activation. This construct undergoes selective cleavage by matrix metalloproteinases (MMPs) that are highly expressed in the TME to release highly penetrant, free, low-molecular-weight IL-12 locally. This tumor-restricted activation process directly facilitates the selective recruitment and activation of tumor-infiltrating lymphocytes (TILs). The intravenous administration of an extremely low dose of 108 pmol per dose of αHSA-proIL-12 completely cleared MC38 tumors without inducing systemic toxicity. The maximum tolerated dose of this molecule exceeded 2 nmol, yielding a remarkably wide therapeutic index >18.5. Mechanistically, αHSA-proIL-12 effectively reprogrammed the immunosuppressive TME by expanding the numbers of effector CD8⁺ T cells and natural killer cells while upregulating IFN-γ expression and significantly reducing the proportion of regulatory T cells. This immunological remodeling has the potential to convert “cold” tumors into “hot” tumors. Notably, this treatment achieved complete regression and durable immunity in a subset of mice with multiple refractory immune-cold tumors, including Panc02 pancreatic cancer, 4T1 triple-negative breast cancer, and B16F10 melanoma, when administered as a monotherapy or in combination with PD-L1 blockade. Furthermore, when combined with surgery, αHSA-proIL-12 effectively prevented the postoperative recurrence and distant metastasis of advanced 4T1 tumors. This modular platform provides a clinically promising strategy to overcome the toxicity bottleneck of cytokines and substantially advances the development of combination cancer immunotherapies. Full article

Background/Objectives: Accurate preoperative detection of locally advanced breast cancer is essential for neoadjuvant therapy planning. We developed and validated gradient-boosting models using structured BI-RADS mammographic features to simultaneously predict locally advanced breast cancer (LABC), DCIS component, and multifocality in a multi-center cohort. Methods: This retrospective study enrolled 2295 patients from three university-affiliated hospitals; features were coded according to BI-RADS. CatBoost and logistic regression models were built using stratified 60/20/20 splits, with performance assessed via bootstrap resampling, nested cross-validation, and sensitivity analyses. AUROC, AUPRC, Brier score, and calibration metrics assessed discrimination and clinical utility; a leakage audit and SHAP analysis supported interpretation. Results: CatBoost achieved an AUROC of 0.906 (95% CI: 0.876–0.932) for LABC. Because several top predictors overlap with the anatomical criteria defining this outcome, we repeated the analysis excluding them; the reduced model retained a mean AUROC of 0.739, indicating genuine predictive signal beyond the staging overlap. Net benefit was positive across all relevant thresholds, with calibration error of 0.053. DCIS prediction was highly accurate (AUROC 0.979; nested AUROC 0.9707), with no evidence of leakage. Multifocality prediction was more modest (AUROC 0.810), reflecting known limits of two-dimensional mammography. Sensitivity analyses confirmed stable performance across splits, training sizes, and class-weighting schemes. Conclusions: Structured mammographic features combined with gradient-boosting support clinically meaningful, though partly overlapping, risk stratification for LABC; once accounted for, the model still retains independent value. The DCIS model performed very well; multifocality prediction remains more limited, and external validation is needed before clinical use. Full article

Breast cancer relapse in bone is a significant clinical problem that is experienced in ~70–80% of patients with late-stage breast cancer. This condition commonly occurs 5–10+ years following surgical removal of the primary tumour. The long latency seen prior to relapse in bone is a result of tumour cell dormancy. Once disseminated to the bone, tumour cell interaction with the bone metastatic niche (endosteal niche and endovascular cells) maintains cells in a dormant state until changes to the local environment activate the niche to support outgrowth. Amassing evidence suggests that cytokines are key regulators of the bone metastatic niche, controlling bone homing and metastatic outgrowth. Pro-inflammatory cytokines, including IL-1β, IL-6, IL-8, TGFβ and RANKL, play crucial roles in attracting tumour cells to bone. Furthermore, these cytokines act in conjunction with IFN, VEGF, TGF, PTHrP, FGF, OPG and various chemokines to regulate expansion of the niche, facilitating tumour cell escape from dormancy and promoting the “vicious cycle of bone metastasis”. Here, we review the current literature to provide an up-to-date understanding of how interactions between cytokine signalling cascades regulate the bone metastatic niches to promote homing, dormancy or metastatic outgrowth of breast cancers. Because breast cancers are predominantly osteolytic, this review focuses on dormancy and metastatic outgrowth associated with lytic disease in addition to current advances in novel therapeutics aimed at preventing this condition through targeting dormant cells. Full article

Purpose: Breast cancer screening relies primarily on two-dimensional (2D) digital mammography, which is limited by tissue superposition and compression-related patient discomfort. Dedicated spiral breast computed tomography (BCT) overcomes these limitations by providing isotropic, fully three-dimensional (3D) volumetric images without compression. However, translating artificial intelligence (AI) advancements to 3D BCT lesion detection is hindered by the scarcity of large-scale annotated 3D datasets and substantial computational constraints. The purpose of this study is to evaluate the feasibility of repurposing a pre-trained 2D mammography AI model for 3D BCT malignancy detection without dedicated model retraining. Methods: In this exploratory proof-of-concept study, the dataset comprised BCT examinations of female patients with malignant lesions. We developed a slab projection framework that systematically rotates the BCT volume and extracts overlapping tissue slabs to simulate mammography-like 2D images compatible with the input requirements of the pre-existing 2D mammography model. The 2D inferences were subsequently back-projected to their original 3D spatial coordinates and aggregated via a consensus voting scheme. Optimization and performance evaluation were performed on the same dataset to establish an internal baseline. Object-level detection performance was assessed using the F1 score, and segmentation quality was evaluated using the Dice coefficient. Results: Application of the proposed framework enabled 3D lesion localization in BCT volumes without requiring domain-specific training. An optimal configuration was found with a sparser angular sampling combined with medium slab thickness (45° angular spacing, 50-voxel thickness), which achieved an F1 score of 0.346, with 48.3% precision and 26.9% recall. Evaluation of segmentation quality corroborated these findings, yielding a maximum mean Dice coefficient of 0.336 for the 45°/30-voxel configuration. Conclusions: This exploratory proof-of-concept demonstrates the technical feasibility of adapting a pre-trained 2D mammography AI model to volumetric BCT without architectural modifications or retraining. The reported performance represents an internal same-dataset baseline under substantial domain shift and should not be interpreted as generalizable or clinically deployable performance. These findings provide a foundation for future domain-adapted models and independent external validation of AI-based tumour detection in breast CT. Full article

Breast cancer treatment still faces challenges including local recurrence, systemic toxicity, tumor heterogeneity, drug resistance, and immunosuppression. Conventional systemic administration provides limited exposure at the tumor site and exhibits significant toxicity. Injectable hydrogels, combining the properties of minimally invasive administration, in situ gelation, local retention, and sustained release, have become a key platform for local precision drug delivery. Compared with nanomedicines or free drugs, hydrogels can both prolong drug retention time and achieve on-demand release through the modulation of crosslinking density, degradation rate, and responsive chemical bonds. This review is organized around the material logic of such systems. Injectable hydrogels are first classified into natural, synthetic, hybrid, supramolecular, nanocomposite, and self-healing systems, the in situ gelation chemistries available to each are compared, and network parameters such as crosslinking density, mesh size, swelling, porosity, modulus, and rheology are related to release kinetics and intratumoral retention. Current research is primarily advancing along two directions: one is the construction of pH-, enzyme-, redox/ROS-, hypoxia-, ATP-, glucose-or thermo-responsive hydrogels; the other is achieving active targeting by integrating functionalized hydrogels with targets such as CD44, folate receptor, integrins, EGFR, transferrin receptor, and HER2 or with biomimetic cell-membrane coatings. On this basis, hydrogels have been extended to cancer vaccines, immune checkpoint modulation, local delivery of CAR-T/CAR-NK, as well as combination therapies involving chemotherapy, photothermal therapy, photodynamic therapy, chemodynamic therapy, sonodynamic therapy, radiosensitization, gene therapy, and theranostics. The constraints imposed on hydrogel design by different payload classes, including small molecules, natural products, proteins and peptides, nucleic acids, antibodies, exosomes, and gene-editing machinery, are further examined, and imaging-integrated theranostic gels are discussed together with the emerging role of machine learning and digital fabrication in hydrogel optimization. Based on the biological foundations of breast cancer, this review summarizes advances in the material design, microenvironment-responsive release, targeting strategies, immunomodulation, and combination therapy of hydrogels, critically evaluates the limitations of each strategy, and aims to provide a reference for the design of mechanistically well-defined and translatable hydrogel delivery systems for breast cancer. Full article

Exosomes are small extracellular vesicles that mediate intercellular communication and, in cancer, carry cargo that both reflects the donor tumor cell and influences recipient cells within local and distant microenvironments. Exosomal proteins and microRNAs have been reported individually across many cancer types, but rarely compared on a common basis; in this review, previously reported molecules from eight cancer categories—blood, breast, colon, kidney, liver, lung, prostate, and stomach—were compiled from curated repositories and re-analyzed within a single functional framework. In total, 3643 exosomal proteins (523 hematologic, 3120 solid-tumor) and 627,225 miRNA–target pairs, derived from 350 unique microRNAs, were organized using Gene Ontology, KEGG, and PANTHER annotation. Across cancers, proteins converged on a reproducible core—signaling, transport, cytoskeletal organization, and extracellular interaction—dominated by binding, catalytic, and transporter functions localized to membrane, vesicle, and extracellular compartments. Comparisons between hematologic and solid malignancies revealed both shared cancer-associated functions and context-dependent patterns linked to tissue origin and disease ecology. Together, these findings indicate that integrated protein-and-microRNA profiling offers a useful framework for understanding tumor communication, refining cancer classification, and advancing biomarker discovery, while underscoring that harmonized workflows, independent validation, and mechanistic follow-up remain necessary before descriptive enrichment outputs can support clinically robust applications. Full article

Breast cancer is among the most common cancers globally. While several advancements have been made to improve breast cancer management, there is still a need to find innovative ways to deliver drug therapy to improve efficacy and side effects associated with treatment. Among these methods, local and targeted drug delivery is particularly promising. The current review highlights localized polymer-based methods to effectively deliver breast cancer therapy, with a specific focus on the strengths and limitations of these systems. Injectable and surgically implanted scaffolds, microneedles, topical patches, liquid and semisolid topical drug carriers are amongst some of the delivery systems discussed. Highlighted in the discussion is how physiological changes that occur during breast cancer should be considered and utilized when developing drug formulations, by specifically exploiting the tumor microenvironment. Remaining gaps and future areas for drug delivery research are highlighted including personalized medicine and insights into novel drug delivery systems like nanomedicines and three-dimensional drug printing. Full article

Calcium signaling is a fundamental regulator of cell physiology, controlling proliferation, differentiation, migration, metabolism, gene expression, and cell death. In cancer, these signaling pathways are extensively remodeled to generate spatially and temporally restricted Ca²⁺ signals that support malignant progression while avoiding calcium-induced cytotoxicity. PMCAs traditionally regarded as high-affinity calcium extrusion pumps, have recently emerged as multifunctional regulators of compartmentalized calcium signaling. In addition to maintaining low cytosolic Ca²⁺ concentrations, PMCA isoforms organize specialized signaling microdomains by interacting with receptors, ion channels, scaffold proteins, and downstream signaling molecules, thereby selectively modulating calcium-dependent pathways involved in tumor growth and metastasis. Accumulating evidence demonstrates that PMCA isoforms exert distinct, context-dependent functions in cancer. PMCA1 primarily contributes to basal calcium homeostasis but has also been implicated in tumor progression, angiogenesis, and regulation of the tumor immune microenvironment. PMCA2 promotes survival and oncogenic signaling in HER2-positive breast cancer through stabilization of receptor signaling complexes. PMCA3 has been linked mainly to endocrine tumors and selected malignancies, although mechanistic evidence remains limited. PMCA4 exhibits the greatest functional diversity, acting either as a tumor suppressor or a promoter depending on the cancer type by regulating localized calcium signaling, cell migration, invasion, differentiation, and interactions with oncogenic signaling networks. This review summarizes current advances in the structural biology, regulation, and signaling functions of PMCA isoforms, with particular emphasis on their emerging roles in cancer biology. We also discuss the potential of PMCAs as prognostic biomarkers and therapeutic targets, highlighting the importance of isoform-specific strategies for targeting calcium signaling in cancer. Full article

Background: Breast cancer treatment is often based on multimodal approaches in locally advanced stages typically including neoadjuvant chemotherapy (NACT). There are limited options for the assessment of prognosis and early identification of future non-responders, which has led to the study of circulating cell-free DNA (cfDNA) and its tumor-derived subset, circulating tumor DNA (ctDNA), for potential use as non-invasive markers for prediction of response and prognosis associated with NACT. Methods: We have evaluated the literature on approaches to the use of cfDNA and/or ctDNA as potential biomarkers for NACT. Results: Out of 142 references going back to 2010, we found there were 87 original research reports, 39 reviews, 10 clinical trial reports and six case reports. A detailed analysis revealed several distinctive ways that markers were evaluated in a clinical setting. The original studies have focused on cfDNA, especially cfDNA integrity, whereby increasing integrity levels correlate with tumor shrinkage, reductions in proliferation markers, and hence indicate a better prognosis. Similarly, epigenetic alterations have shown promising results, with methylated ctDNA levels decreasing in responders. Further studies demonstrated the utility of ctDNA persistence through the NACT as strongly associated with shorter disease-free and overall survival. The most recent approaches of longitudinal ctDNA monitoring were found to be valuable for early identification of patients at high risk for post-operative recurrence. Conclusions: It should be noted that while most reports indicate the important role of circulating DNA in the assessment of prognosis and early detection of recurrence, there is currently only a limited utility in the prediction of eventual neoadjuvant therapy outcomes. Full article

Breast cancer remains one of the most prevalent malignancies affecting women worldwide and continues to be a leading cause of cancer-related morbidity and mortality. Patients may present with either localized or advanced disease, with clinical outcomes increasingly influenced by molecular subtype and genetic profile. This review highlights the key genetic factors involved in breast cancer, current diagnostic and therapeutic strategies, and promising emerging approaches that may shape future clinical management. Breast cancer diagnosis typically involves clinical breast examination, imaging techniques such as mammography and ultrasound, and confirmatory biopsies. Genetic mutations in specific genes are strongly linked to the development, progression, and metastasis of the disease. Treatment options for localized breast cancer continue to include surgery (lumpectomy or mastectomy) and radiotherapy, combined with systemic therapies tailored to tumor biology, such as endocrine therapy, human epidermal growth factor receptor 2 (HER2)-targeted therapy, and cyclin-dependent kinase (CDK)4/6 inhibitors. For advanced or metastatic breast cancer, recent therapeutic advances include the use of immunotherapy (e.g., immune checkpoint inhibitors), Poly (ADP-ribose) polymerase (PARP) inhibitors for Breast Cancer gene (BRCA)-mutated cancers, antibody–drug conjugates, and novel targeted agents, which have significantly improved patient outcomes in selected populations. Recent findings in breast cancer genetics have highlighted the critical role of germline and somatic mutations, particularly in genes such as BRCA1, BRCA2, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), and TP53, in driving tumor initiation, progression, and therapeutic response. Molecular profiling and next-generation sequencing technologies have enabled more precise tumor classification and facilitated the development of personalized treatment strategies. Despite these advances, treatment resistance and disease recurrence remain major challenges, particularly in aggressive subtypes such as triple-negative breast cancer. Consequently, ongoing research is exploring alternative and complementary approaches, including nanotechnology-based drug delivery systems, gene editing techniques such as clustered regularly interspaced short palindromic repeats-Cas9 (CRISPR-associated protein 9) (CRISPR-Cas9), cancer vaccines, and the integration of traditional and plant-derived compounds. These strategies aim to enhance therapeutic efficacy, reduce systemic toxicity, and overcome resistance mechanisms. Full article

Background/Objectives: Older women with breast cancer carry a high burden of frailty, depressive symptoms and cognitive complaints, yet how these domains relate to one another in routine clinical practice remains incompletely understood. We examined the prevalence of positive frailty screening and its association with patient-reported cognitive function and asked whether depressive symptoms account for the apparent link between the two. Methods: We analyzed 314 women aged 65 years or older with stage IIB–IIIC breast cancer who underwent a standardized geriatric assessment. Measures included the G8 screening tool, Vulnerable Elders Survey-13 (VES-13), Geriatric Depression Scale (GDS), Instrumental Activities of Daily Living (IADL), cognition and quality of life (FACT-Cog, FACT-G, and EORTC QLQ-C30). Associations were examined using correlation analyses, group comparisons, and multivariable linear regression. Results: Mean age was 72.9 years. A positive frailty screen (G8 ≤ 14) was present in 295 patients (93.9%), and 102 patients (32.5%) screened positive for depressive symptoms (GDS ≥ 5). G8 screening score correlated strongly with patient-reported cognitive function (Pearson r = 0.80, p < 0.001), and patients with a positive frailty screen reported lower FACT-Cog scores than those with a negative screen (113.0 vs. 129.0, p < 0.001). In multivariable analysis adjusted for age and G8 score, depressive symptoms emerged as the strongest independent correlate of FACT-Cog (β = −0.89, p < 0.001; model R² = 0.90), whereas G8 screening score was no longer independently associated (p = 0.16). Patients with depressive symptoms had more than double the VES-13 vulnerability score of those without (7.8 vs. 3.6, p < 0.001). Overall geriatric assessment profiles were generally comparable across the three exploratory treatment-era cohorts. Conclusions: In this cross-sectional analysis of older women with locally advanced breast cancer, depressive symptoms were the strongest independent correlate of patient-reported cognitive function. Incorporating a brief depression screen into routine geriatric assessment may represent a clinically actionable target that deserves further evaluation. Full article

Background/Objectives: Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype characterized by substantial biological heterogeneity and variable clinical outcomes. Reliable prognostic tools are needed to improve risk stratification following neoadjuvant chemotherapy (NACT). This study aimed to evaluate the association of the Clinical–Pathologic Stage, Estrogen/Grade (CPS-EG) score with pathological complete response (pCR) and survival outcomes in patients with locally advanced TNBC treated with NACT. Methods: In this multicenter retrospective cohort study, 690 patients with locally advanced TNBC treated with NACT between 2010 and 2024 at 25 oncology centers were included. Patients were categorized according to CPS-EG score (≤3 vs. >3). Associations between CPS-EG score, clinicopathological characteristics, pCR, disease-free survival (DFS), and overall survival (OS) were analyzed. Survival outcomes were evaluated using Kaplan–Meier and Cox regression analyses. Results: Patients with a CPS-EG score > 3 had significantly lower pCR rates and higher recurrence rates compared with those with a CPS-EG score ≤ 3 (p < 0.001 for both). Five-year OS rates were 83.7% and 54.1% in the CPS-EG ≤ 3 and > 3 groups, respectively, while the corresponding five-year DFS rates were 76.4% and 51.9% (p < 0.001 for both). In the multivariable analysis, CPS-EG > 3 remained independently associated with worse OS (HR 1.46, 95% CI 1.08–1.98, p = 0.015) and DFS (HR 1.73, 95% CI 1.26–2.38, p < 0.001). Conclusions: A higher CPS-EG score is associated with a lower likelihood of achieving pCR and poorer long-term survival outcomes in patients with locally advanced TNBC treated with NACT. The CPS-EG score represents a simple and readily available tool that may support risk stratification and clinical decision-making in routine practice. Full article