Search Results (2,337)

Metastatic breast cancer (MBC) remains incurable because of tumor evolution. Despite advances in targeted therapies—CDK4/6 inhibitors, PIK3 inhibitors, HER2-directed agents, and antibody–drug conjugates—median overall survival is modest, with resistance emerging in nearly all patients. From an evolutionary perspective, standard continuous maximum tolerated dose (MTD) therapy may create intense selective pressure that reduces treatment-sensitive cells and, in some incurable and resistance-prone settings, could permit competitive release of resistant clones. While MTD remains the guideline-endorsed standard of care in many metastatic settings and has produced substantial survival gains, the eco-evolutionary framework highlights a potential trade-off rather than a categorical failure of MTD. Cancer is not just a genetic disease but an evolving ecosystem where cell populations compete for limited resources. Resistant cells typically carry a fitness cost—slower growth in the absence of treatment—creating an exploitable vulnerability. By preserving treatment-sensitive cells through dose modulation or treatment holidays (adaptive therapy), we can harness competitive suppression to control resistant populations and prolong disease control, potentially doubling time to progression compared to continuous MTD. This primer translates these ideas into plain language for clinical trial application. We explain four core eco-evolutionary principles every breast oncologist should know, review emerging evidence from adaptive therapy trials in breast and other cancers, and discuss practical implementation strategies to incorporate into future trials. The goal is not cure through eradication, but long-term control through evolutionary management. These evolution-informed strategies may, in selected contexts, help delay resistance and prolong disease control, and represent a complementary framework that warrants prospective testing. Full article

LIM and calponin homology domain-containing protein 1 (LIMCH1) has recently gained attention as a functionally perplexing factor in human cancers, with studies attributing both tumor-suppressive and tumor-promoting properties that defy simple categorization. Originally described as an actin-associated cytoskeletal protein that promotes non-muscle myosin-IIA (NM-IIA) activity and thereby curtails cell migration, LIMCH1 has more recently been linked to diverse oncogenic pathways across a range of tumor types. In lung adenocarcinoma and clear-cell renal cell carcinoma, diminished LIMCH1 expression is associated with more aggressive clinical behavior and reduced overall survival, aligning with a tumor-suppressive role. By comparison, in triple-negative and invasive breast cancers and in cervical squamous cell carcinoma, increased LIMCH1 expression correlates with enhanced metastatic spread, immune escape, and unfavorable outcomes, suggesting a pro-oncogenic function. In this review, findings from over 30 published studies are integrated with an original TCGA pan-cancer expression and survival analysis to propose that LIMCH1 is best understood as a context-dependent conditional regulator rather than as a classical tumor suppressor or oncogene. Based on the available evidence, we propose a hypothesis-generating conceptual framework in which its ultimate phenotypic effect is shaped by three interacting contextual determinants: (i) TP53 mutation status (determining whether the HUWE1-p53 axis is intact); (ii) tumor matrix stiffness (modulating actomyosin contractility and migration mode); and (iii) upstream signaling cues (e.g., MAPK/ERK, TGFβ). Of note, other tumor-lineage and microenvironmental factors may also contribute and warrant further investigation. This framework resolves the apparent functional duality of LIMCH1 in a cancer type-specific manner and provides critical guidance for future mechanistic research, standardized detection workflows, and the clinical translation of LIMCH1-based biomarkers. Full article

Background/Objectives: Breast cancer is the most common malignancy among women worldwide and poses a significant burden on healthcare systems. Despite evidence that treatment type is associated with hospital length of stay (LOS), current Germany-wide data on this topic are lacking. The present study aims to identify clinical and procedural factors associated with prolonged hospitalisation in women hospitalised for breast cancer in Germany. Methods: This multicentre cross-sectional study analysed anonymised inpatient data from 38 German hospitals (IQVIA database), including 16,062 female breast cancer hospitalisation episodes (inpatient cases; patient-level linkage was not possible due to anonymisation, so these may not represent 16,062 distinct women) treated between January 2019 and December 2024. The primary outcome was LOS; prolonged hospitalisation was defined as LOS > 7 days (75th percentile). Comorbidities were assessed using individual comorbidity categories defined according to the Elixhauser classification (retained at ≥1% prevalence). The primary multivariable analysis was restricted to characteristics documented independently of the in-hospital course (age, tumour site, metastatic status, chronic comorbidities). In-hospital complications, procedures, and diagnoses of ambiguous timing were analysed separately as secondary, descriptive associations. LOS was modelled using negative binomial regression (Poisson regression as a sensitivity analysis) and prolonged LOS using logistic regression, both with hospital-clustered robust (sandwich) standard errors. Results: The overall median LOS was 4 days (IQR 3–7); 19.3% of hospitalisation episodes were prolonged. In the primary analysis, longer LOS was associated with age > 70 years (RR 1.14; 95% CI 1.08–1.20), distant metastases (RR 1.76; 95% CI 1.51–2.04), lymph node metastases (RR 1.09; 95% CI 1.05–1.12), congestive heart failure (RR 1.44; 95% CI 1.31–1.59), anaemia (RR 1.41; 95% CI 1.14–1.75) and depression (RR 1.14; 95% CI 1.03–1.26). In the secondary descriptive analysis, in-hospital complications showed the strongest associations with longer LOS, particularly postoperative infection (RR 2.28), wound disruption (RR 1.92) and pneumonia (RR 1.45). Breast-conserving surgery and partial breast resection were associated with shorter LOS, while mastectomy, blood transfusions, and complex intensive care were associated with prolonged stays; the small inpatient radiotherapy subgroup (1.9%) most likely reflects a highly selected, predominantly palliative population rather than an association attributable to radiotherapy itself. Conclusions: Prolonged hospitalisation was associated with older age, documented lymph node and distant metastases, and chronic somatic comorbidities including congestive heart failure, anaemia, chronic kidney disease and depression, and, in secondary descriptive analyses, with perioperative complications and intensive procedures. The strongest correlates of prolonged stay—in-hospital complications and intensive procedures—are documented during rather than before the hospitalisation and therefore cannot themselves support early risk identification; however, the baseline characteristics documented independently of the in-hospital course (age, metastatic disease, chronic comorbidity burden) may usefully inform structured perioperative management and discharge planning in Germany. Full article

Background: Metabolic adaptability plays a critical role in supporting the growth and survival of metastatic breast cancer cells, and potentially supports site-specific metastasis. This study investigates the differential metabolism of glutamine and adaptability to varying glutamine levels of triple-negative breast cancer (TNBC) cells that metastasize to the lungs (metM-Wnt^Lung) or liver (metM-Wnt^Liver). Methods: The metastatic cell lines were exposed to varying in vitro glutamine concentrations (0.5, 2, and 4 mM). Cell viability, migration, ¹⁴C-glutamine uptake, mRNA abundance of metabolic enzymes, and ¹³C₅-glutamine cellular flux, were measured. Results: At an intermediate level of in vitro glutamine supplementation (2 mM), metM-Wnt^Lung cells exhibited greater glutamine uptake, catabolic enzyme expression, and flux of glutamine-derived carbon into the TCA cycle compared with metM-Wnt^Liver cells. Despite this, metM-Wnt^Liver cells were more viable and migratory than metM-Wnt^Lung cells under both higher (4 mM) and lower (0.5 mM) glutamine levels, suggesting metabolic adaptability. Exposure to ammonia upregulated ammonia-assimilating enzymes in metM-Wnt^Liver, but not metM-Wnt^Lung cells, plausibly mitigating ammonia toxicity in higher glutamine conditions. In glutamine-deprived conditions, the metM-Wnt^Lung cells maintained higher glutamine oxidation, but the metM-Wnt^Liver cells had higher total glutathione and GSH/GSSG ratios and enhanced resistance to oxidative stress, suggesting glutamate utilization toward glutathione synthesis. Additionally, metM-Wnt^Liver cells utilized glucose-derived carbons through pyruvate carboxylase (PC) to maintain TCA cycle activity, with elevated PC expression and M+3-labeled oxaloacetate enrichment to a greater extent than metM-Wnt^Lung cells. PC silencing in metM-Wnt^Liver cells enhanced cell viability under glutamine deprivation, which was reversed by inhibiting phosphoglycerate dehydrogenase (PHGDH, a key enzyme in de novo serine synthesis). We propose that PC activity compensates for low glutamine levels, including diverting glucose to adaptive pathways such as de novo serine synthesis. Conclusions: Overall, our findings demonstrate that metM-Wnt^Liver cells, but not metM-Wnt^Lung cells, exhibit glutamine-specific metabolic plasticity, characterized by the modulation of glutamine catabolism, enhanced ammonia metabolism and antioxidant defense, and support of glucose metabolism, which are associated with better cell survival and migration under glutamine excess and deprivation. Full article

Breast cancer remains one of the leading causes of global mortality, which has growing driving interest in dietary natural products for potential chemopreventive and complementary approaches. Cherries (Prunus species) are rich in bioactive phytochemicals, notably anthocyanins, hydroxycinnamic acids, and the flavonols quercetin and kaempferol. This review aims to examine and discuss current research on the molecular targets and mechanisms of action of whole cherry extracts and their primary flavonols quercetin and kaempferol across various breast cancer subtypes. Preclinical studies indicate that these compounds exert multi-targeted effects by inducing apoptosis, inhibiting cell proliferation, and suppressing metastatic pathways. Additionally, these flavonols show potential in reversing multidrug resistance. A whole-food approach highlights the candidate synergistic properties of these phytochemical complexes, but low oral bioavailability and rapid metabolism severely limit their clinical translation. Therefore, utilizing innovative drug delivery systems remains crucial to improving their stability, absorption, and overall therapeutic efficacy. Full article

Background and Objectives: Intraoperative sentinel lymph node (SLN) assessment is a pivotal step in early-stage breast cancer surgery. Frozen section (FS) analysis remains a widely utilised technique; however, its limitations, particularly in the detection of micrometastases, are well-documented. The process is both time-consuming and costly. The objective of this study was to investigate the potential of ex vivo shear-wave elastography (SWE) as a rapid and reproducible method for quantifying lymph node stiffness and predicting metastatic involvement. Materials and Methods: Between January 2022 and January 2024, 100 patients with biopsy-confirmed invasive breast cancer undergoing SLNB were enrolled in the study. A total of 384 excised axillary lymph nodes were subjected to ex vivo SWE immediately following excision, prior to the standard histopathological procedure. The mean stiffness (Emean) values were recorded, and the diagnostic performance was evaluated with the use of ROC analysis. Results: Of the 384 nodes examined, 45 (11.6%) were found to have metastases on final histopathology. It was demonstrated that Emean exhibited excellent discriminatory power, with an Area Under the Curve (AUC) value of 0.957. At the optimal cut-off of 28 kPa, the sensitivity and specificity levels were recorded as 91% and 87%, respectively. Conclusions: The findings of this study indicate that ex vivo SWE is a highly accurate and reproducible method for identifying metastatic sentinel lymph nodes. The technique has the potential to complement or selectively replace intraoperative FS, thereby reducing unnecessary tissue processing. The logical next step is multicentre validation. Full article

Background/Objectives: In metastatic breast cancer (MBC) treated with CDK4/6 inhibitors, baseline neutrophil-to-lymphocyte ratio (NLR) is an established prognostic marker. On-treatment NLR dynamics have shown inconsistent associations with survival, and no prior study has applied a dominant-driver decomposition to classify patients by whether NLR change is neutrophil- or lymphocyte-driven. Methods: We retrospectively analyzed 352 patients with HR+/HER2− MBC treated with ribociclib. Using paired neutrophil and lymphocyte counts at baseline and at approximately 12 weeks (before cycle 4), a log-linear decomposition classified patients into four NLR-trajectory phenotypes by the dominant driver of change. Associations with progression-free survival (PFS) and overall survival (OS) were assessed using a 4-month landmark approach with multivariable Cox models, with consistency evaluated across four thresholds, tertiles, and a continuous model. Secondarily, NLR change was compared across five response-trajectory groups. Results: NLR trajectory was not associated with PFS in any specification (multivariable hazard ratio [HR] 1.15 per standard deviation [SD], 95% CI 0.97–1.37, p = 0.12) but was independently associated with OS (HR 1.40 per SD, 95% CI 1.18–1.67, p < 0.001), confirmed on bootstrap resampling. Adding NLR trajectory improved discrimination (C-index +0.04) and fit (likelihood-ratio p < 0.001). The OS effect was time-varying, attenuating beyond 24 months. NLR trajectory was unrelated to dose-limiting neutropenia (p = 0.58) or dose reduction (p = 0.69). Primary refractory patients showed blunted NLR decline versus responding or stable patients (p = 0.005), independent of baseline NLR. Conclusions: On-treatment NLR trajectory is a correlate of OS, independent of PFS, dose-limiting neutropenia, and dose reduction, in ribociclib-treated MBC, distinct from direct tumor control. Prospective validation is warranted. Full article

Purpose: Trastuzumab deruxtecan (T-DXd) has significantly improved outcomes in patients with HER2-positive and HER2-low/ultralow metastatic breast cancer (MBC). However, most patients eventually discontinue treatment. In clinical trials, discontinuation without disease progression occurred in 30–60% of cases, but real-world data on the reasons for discontinuation and subsequent treatment strategies remain limited. This study aimed to describe T-DXd discontinuation patterns and post-discontinuation treatments in a real-world setting. Methods: We conducted a single-center retrospective observational study including consecutive patients with MBC treated with T-DXd between July 2018 and December 2025. Patients who discontinued T-DXd for any reason were included. Reasons for discontinuation, treatment duration, response outcomes, and subsequent systemic therapies were analyzed using descriptive statistics. Results: Overall, 93 patients were included: 71.0% had HER2-positive, 26.9% HER2-low, and 2.1% HER2 0 tumors. The primary reason for discontinuation was progressive disease (82.8%). Other reasons included adverse events (14.0%), non-treatment-related causes (2.2%) and patient decision (1.1%). Interstitial lung disease represented the most common toxicity leading to discontinuation (10.8%). The median treatment duration was 7.9 months overall and was longer in patients with HER2-positive than in thosewith HER2-low and HER2 0 disease. Among evaluable patients, overall response rate was 83.1% in HER2-positive tumors and 52% in HER2-low tumors. After discontinuation, 80.6% of patients received subsequent therapy. Patients discontinuing for reasons other than progression had longer treatment exposure. Conclusions: In this real-world cohort, most T-DXd discontinuations were due to disease progression, while adverse event-related discontinuations were less frequent than in clinical trials. Several factors may influence treatment persistence, including toxicity management. Further evaluation in larger, multicenter cohorts is warranted to better characterize their contribution. Full article

De-escalation of axillary surgery has resulted in the loss of pathologic nodal information, yet the extent of lymph node involvement remains an important determinant of treatment decisions in estrogen receptor-positive (ER+)/HER2− disease. We examined whether primary tumors differed molecularly according to the extent of this regional dissemination. Genome-wide DNA methylation profiling of primary ER+/HER2− tumors from 47 patients with pN1 (n = 29) vs. >pN1 (n = 18) disease showed differences concentrated at promoters of developmental and cell-adhesion genes. By integrating methylomes with transcriptomes from the TCGA-BRCA cohort (n = 148) and clinical outcomes from KM Plotter (RFS, n = 1154; OS, n = 442; DMFS, n = 423), we identified four genes (ARL10, RIC3, CXCL14, KCNH2) showing concordant molecular and clinical associations, from which we derived the Lymph-node Involvement Outcome Numerator (LION) score. Lower LION scores were observed in metastatic lesions from the AURORA US cohort (n = 45). In SCAN-B (n = 3969), lower scores were associated with shorter distant recurrence-free intervals (HR = 0.38; 95% CI 0.23–0.62); this association persisted after adjustment for age, nodal and tumor category but was lost after adjustment for histological grade (HR = 0.83; 95% CI 0.48–1.44), indicating that the score and grade capture overlapping biology. These findings suggest that primary tumors already display coordinated epigenetic and transcriptional alterations associated with the extent of metastatic dissemination. Full article

Objective: We aimed to investigate whether ultrasound-based texture analysis can differentiate liver metastases according to the histopathological origin of the primary tumor and to evaluate the quantitative texture characteristics of metastases originating from colorectal, pancreatic, and breast cancer. Materials and Methods: This prospective study included 75 patients with biopsy-proven liver metastases, comprising 25 colorectal adenocarcinoma, 25 pancreatic ductal adenocarcinoma, and 25 invasive ductal breast carcinoma metastases. Conventional B-mode ultrasound images were obtained prior to treatment. The largest metastatic lesion in each patient was manually segmented using a whole-lesion two-dimensional region of interest (ROI). Histogram-based texture analysis was performed using an in-house MATLAB-based software package (version R2021a; MathWorks, Natick, MA, USA). Extracted parameters included intensity-based metrics, dispersion measures, entropy, uniformity, and percentile values. Texture features were compared among the three groups using appropriate statistical tests. Results: Significant differences were observed among metastatic lesions according to their primary tumor origin. Significant differences were observed in the mean, median, minimum, maximum, most frequent gray-level values, root-mean-square level, root-sum-of-squares level, entropy, and all evaluated percentile parameters among groups (all p < 0.05). Pancreatic cancer metastases consistently demonstrated the highest intensity-related histogram values and percentiles, whereas breast cancer metastases exhibited the lowest values. Colorectal metastases were generally of intermediate intensity. Entropy values were significantly higher in colorectal and pancreatic metastases than in breast cancer metastases (p < 0.05), suggesting greater structural heterogeneity. No significant differences were observed for kurtosis, skewness, uniformity, or size distribution parameters (all p > 0.05). Conclusions: Ultrasound-based tissue analysis revealed distinct quantitative features among liver metastases originating from colorectal, pancreatic, and breast cancer. Density-related parameters, percentiles, and entropy show the potential to differentiate metastatic lesions based on their primary tumor origin, thus serving as a non-invasive biomarker. Full article

Background/Objectives: The prognostic nutritional index (PNI) has been associated with outcome in metastatic breast cancer, but studies in CDK4/6 inhibitor-treated patients have used cohort-derived thresholds and examined only the pretreatment value. We assessed the PNI as a continuous variable, compared it with inflammatory indices, and examined whether repeated measurement added information. Methods: We reviewed 192 consecutive patients with hormone receptor–positive, HER2-negative metastatic breast cancer treated with a CDK4/6 inhibitor and endocrine therapy at a single centre. We calculated the PNI, neutrophil-to-lymphocyte ratio (NLR), and systemic inflammation response index (SIRI) before treatment and recalculated them before cycles 2 and 3. The Cox models were adjusted for age, liver metastasis and line of therapy; no threshold was derived from these data. Results: The median follow-up was 44.9 months. Each one-point increase in the baseline PNI was independently associated with lower hazards of progression (HR 0.952, 95% CI 0.923–0.983) and death (HR 0.919, 95% CI 0.884–0.956), corresponding to HR 0.782 (95% CI 0.670–0.918) and HR 0.656 (95% CI 0.540–0.799) per five-point increase. For overall survival, in formal comparisons on identical patient sets, neither the NLR nor the SIRI added prognostic information to a model containing the PNI (likelihood ratio p = 0.383 and p = 0.335), whereas the PNI added information to models containing either ratio (p < 0.001 and p = 0.004). In exploratory landmark analyses, change in the PNI added little to the baseline value; apparent associations between increases in the NLR or SIRI by cycle 3 and overall survival did not persist after winsorisation of extreme change scores. Conclusions: Baseline PNI, analysed as a continuous variable and without a data-derived threshold, was independently associated with progression-free and overall survival in this cohort. For overall survival, neither baseline inflammatory ratio added detectable prognostic information beyond the index, and repeated measurement during treatment added little to the baseline value, although the confidence intervals do not exclude modest effects. Because all patients received a CDK4/6 inhibitor and no comparator arm was available, these findings support a prognostic rather than a predictive interpretation, and external validation is required before the index can inform clinical decisions. Full article

The integration of artificial intelligence (AI) into digital histopathology has the potential to improve the accuracy and efficiency of metastatic cancer diagnosis. We evaluated LYDIA (LYmph noDe assIstAnt), an AI-based decision-support system, for both standalone diagnostic performance and its impact on histopathologists’ workflow, diagnostic accuracy, and resource utilization. LYDIA was evaluated on a blinded dataset of 366 whole-slide images (WSIs) from breast, colorectal, lung, and skin cancers. Standalone performance demonstrated excellent discrimination, achieving ROC-AUC values of 0.995, 0.963, 0.973, and 0.983 for breast, colorectal, lung, and skin cancers, respectively. Clinical utility was further assessed in a multi-reader study involving four experienced histopathologists interpreting 105 WSIs with and without AI assistance. AI-assisted diagnosis significantly reduced time-to-diagnosis across all metastasis sizes, with a maximum 1.59-fold acceleration for micro-metastases, corresponding to a mean time saving of 26.5 s per WSI. LYDIA also improved diagnostic sensitivity from 77.3% to 87.3%. These findings demonstrate that LYDIA can enhance both the efficiency and accuracy of lymph node metastasis detection while reducing diagnostic workload and the need for ancillary testing. Beyond improving routine pathology workflows, the system’s rapid inference capabilities and human-expert level performance may support future intraoperative diagnostic applications, enabling timely and automatic or semi-automatic assessment of nodal status to inform surgical decision-making. The resulting reductions in diagnostic time and ancillary testing costs have the potential to improve healthcare resource utilization and patient care, mainly in soft tissue reconstruction and surgical repair decisions. Full article

Background and Aim: Approximately 10% of breast cancer patients present with distant organ metastases at initial diagnosis. This study aimed to evaluate the efficacy of immune-inflammatory markers and histopathological variables in identifying de novo metastatic breast cancer. Methods: Patients with breast cancer referred to a tertiary surgical oncology clinic between January 2020 and December 2022 were retrospectively screened. A total of 412 patients met the strict inclusion criteria. Laboratory parameters and radiological findings obtained during the initial diagnostic workup, prior to the initiation of any therapeutic intervention, were comprehensively evaluated. Results: Among the screened cohort, 56 patients presented with synchronous distant organ metastases at diagnosis. Significant differences (p < 0.05) were observed between the metastatic and non-metastatic groups in serum hemoglobin, albumin, and alkaline phosphatase (ALP) levels, lymphocyte and neutrophil counts, hemoglobin-albumin-lymphocyte-platelet score, prognostic nutritional index (PNI), systemic immune-inflammation index (SII), monocyte-to-lymphocyte ratio, platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio, and pan-immune-inflammation value. Multivariate logistic regression analysis identified Ki-67, T stage, N stage, ALP, SII, and PNI as independent predictors of metastasis (p < 0.05). In the receiver operating characteristic (ROC) analysis, the prognostic score formulated from this predictive model demonstrated an area under the curve (AUC) of 0.821 (95% CI: 0.781–0.857, p < 0.001, and Z-score = 9.34). At an optimal cut-off value of >0.233, the score yielded a sensitivity of 64.3% and a specificity of 92.1%. Furthermore, Decision Curve Analysis (DCA) confirmed a positive net clinical benefit across the decision-making threshold. Conclusions: The developed prognostic score may be a promising clinical tool for differentiating de novo metastatic breast cancer from non-metastatic disease at initial staging. This non-invasive approach may help clinicians risk-stratify patients, reduce diagnostic delays, and optimize early intervention strategies. Nonetheless, larger prospective multicenter studies are warranted for robust validation. Full article

Background: Endobronchial ultrasound (EBUS) is widely used for the diagnosis of pulmonary lesions. When combined with rapid on-site cytologic evaluation (ROSE), it can improve diagnostic accuracy and facilitate early identification of malignancy origin. However, differentiating primary lung cancer from metastatic tumors (e.g., breast or colorectal origin) during ROSE remains challenging due to limited cytopathology support and morphological similarities between tumor cells. This study aimed to develop a computer-aided diagnostic (CAD) system for classifying malignancy types from limited cytological samples to facilitate clinical decision-making. Methods: We utilized a retrospective dataset of cytological images obtained during EBUS procedures between November 2018 and June 2024. The study focused on classifying three malignancies: pulmonary adenocarcinoma, metastatic breast cancer, and metastatic colorectal cancer. A deep learning-based model (PLFCH) was developed, integrating few-shot learning, parameter-efficient fine-tuning, and a hybrid CNN–Transformer architecture to address limited annotated data. Results: A total of 41 patients with 346 cytological images were included. Under a 3-way 5-shot setting, the proposed model achieved an accuracy of 49.26%, outperforming existing few-shot learning methods, with precision, recall, and F1-score of 0.477, 0.493, and 0.480, respectively. Increasing the number of reference images to 20 per class further improved accuracy to 55.48%. Conclusions: The proposed framework demonstrated improved performance for cytological classification under limited data conditions. These findings provide an early proof of concept for applying few-shot learning to cytological assessment during EBUS procedures. Further improvements in model performance and validation in prospective, real-time clinical settings are required before its potential role in assisting diagnostic decision-making can be established. Full article

Background/Objectives: Serum cancer antigen 15.3 (CA 15.3) is frequently measured in advanced breast cancer, but its prognostic significance after adjusting for established clinical factors remains incompletely characterized in Latin American populations. We evaluated the association of baseline CA 15.3 with metastatic burden and overall survival (OS) in hormone receptor-positive/HER2-negative advanced breast cancer and descriptively explored baseline/follow-up patterns. Methods: We retrospectively evaluated 127 women treated at a Peruvian public oncology institution between 2018 and 2024, with CA 15.3 levels ≥32.4 U/mL being considered elevated. Baseline associations were assessed using multivariable logistic regression, and OS was evaluated using Kaplan–Meier estimates and Cox proportional hazards regression adjusted for age, ECOG performance status, de novo versus recurrent disease, luminal subtype, first-line treatment, number of metastatic sites, and metastatic site. Results: Baseline CA 15.3 was elevated in 41/127 patients (32.3%) and was independently associated with postmenopausal status (OR: 3.27; 95% CI, 1.33–9.03; p = 0.014) and ≥2 metastatic sites (OR: 2.72; 95% CI, 1.24–6.10; p = 0.013). Median OS was 55 months (95% CI, 43–78), while elevated baseline CA 15.3 was associated with shorter OS (41 vs. 65 months; log-rank p = 0.024) and remained independently associated with shorter OS after multivariable adjustment (adjusted HR: 3.42; 95% CI, 1.63–7.19; p = 0.001). Conclusions: Elevated baseline CA 15.3 was associated with greater metastatic burden and shorter OS, and baseline/follow-up patterns were exploratory because the sampling was not standardized. Thus, CA 15.3 should be interpreted as an adjunct to clinical and radiological assessment. Full article