Patient and provider perceptions about exercise in cancer care, excluding breast: Are we on the same page?

BackgroundCurrently, the main goal of cancer research is to increase longevity of patients suffering malignant cancers. The promising results of BCc1 in vitro and vivo experiments made us look into the effect of BCc1 nanomedicine on patients with cancer in a clinical trial.MethodsThe present investigation was a randomized, double-blind, placebo-controlled, parallel, and multicenter study in which 123 patients (30-to-85-year-old men and women) with metastatic and non-metastatic gastric cancer, in two separate groups of BCc1 nanomedicine or placebo, were selected using a permuted block randomization method. For metastatic and non-metastatic patients, a daily dose of 3000 and 1500 mg was prescribed, respectively. Overall survival (OS) as the primary endpoint and quality of life (measured using QLQ-STO22) and adverse effects as the secondary endpoints were studied.ResultsIn metastatic patients, the median OS was significantly higher in BCc1 nanomedicine (174 days [95% confidence interval (CI) 82.37–265.62]) than in placebo (62 days [95% CI 0–153.42]); hazard ratio (HR): 0.5 [95% CI 0.25–0.98; p = 0.046]. In non-metastatic patients, the median OS was significantly higher in BCc1 nanomedicine (529 days [95% CI 393.245–664.75]) than in placebo (345 days [95% CI 134.85–555.14]); HR: 0.324 [95% CI 0.97–1.07; p = 0.066]. The QLQ-STO22 assessment showed a mean difference improvement of 3.25 and 2.29 (p value > 0.05) in BCc1 nanomedicine and a mean difference deterioration of − 4.42 and − 3 (p-value < 0.05) in placebo with metastatic and non-metastatic patients, respectively. No adverse effects were observed.ConclusionThe findings of this trial has provided evidence for the potential capacity of BCc1 nanomedicine for treatment of cancer.Trial registration IRCTID, IRCT2017101935423N1. Registered on 19 October 2017, http://www.irct.ir/ IRCT2017101935423N1

The modified Glasgow Prognostic Score (mGPS) by measurement of serum C-reactive protein and albumin levels has been shown to provide prognostic value in various cancer types. The purpose of this study was to evaluate whether preoperative assessment of the mGPS predicts patient survival outcome in renal cell carcinoma (RCC). Clinicopathological and follow-up data in 219 RCC patients, all of whom underwent curative or non-curative nephrectomy, were collected. Overall survival (OS) and cancer-specific survival (CSS) after nephrectomy were evaluated, and univariate and multivariate analyses were conducted to assess the predictive value of the variables, including the mGPS. During the median follow-up of 57months, 53 patients (24.2%) were deceased within 22months of the median OS. The 5-year OS rate from nephrectomy was 85.9 and 18.8% in non-metastatic (n=195) and metastatic (n=24) patients, respectively. Increasing mGPS was associated with shorter OS in non-metastatic patients (2-year OS rate of 98.2% in mGPS0, 73.3% in mGPS1, and 44.4% in mGPS2; hazard ratio [HR] 9.96, 95% confidence interval [CI] 4.88-20.13, p<0.001), whereas no significant difference in OS according to the mGPS was seen in metastatic patients (HR 2.01, 95% CI 0.79-5.16, p=0.137). On multivariate analysis, the mGPS remained as an independent predictor for OS (HR 5.24, 95% CI 1.39-19.77, p=0.015) and CSS (HR 4.69, 95% CI 1.13-20.96, p=0.034) in non-metastatic RCC patients. The mGPS appeared to be a reliable, preoperatively defined predictive marker with widely standardized protocol in non-metastatic RCC, and should therefore be considered in treatment decision making for RCC patients.

BackgroundStratification of cancer patients to identify those with worse prognosis is increasingly important. Through in silico analyses, we recently developed a gene expression-based prognostic score (S3-score) for clear cell renal cell carcinoma (ccRCC), using the cell type-specific expression of 97 genes within the human nephron. Herein, we verified the score using whole-transcriptome data of independent cohorts and extend its application for patients with metastatic disease receiving tyrosine kinase inhibitor treatment. Finally, we sought to improve the signature for clinical application using qRT-PCR.MethodsA 97 gene-based S3-score (S397) was evaluated in a set of 52 primary non-metastatic and metastatic ccRCC patients as well as in 53 primary metastatic tumors of sunitinib-treated patients. Gene expression data of The Cancer Genome Atlas (n = 463) was used for platform transfer and development of a simplified qRT-PCR-based 15-gene S3-score (S315). This S315-score was validated in 108 metastatic and non-metastatic ccRCC patients and ccRCC-derived metastases including in part several regions from one metastasis. Univariate and multivariate Cox regression stratified by T, N, M, and G were performed with cancer-specific and progression-free survival as primary endpoints.ResultsThe S397-score was significantly associated with cancer-specific survival (CSS) in 52 ccRCC patients (HR 2.9, 95% Cl 1.0–8.0, PLog-rank = 3.3 × 10–2) as well as progression-free survival in sunitinib-treated patients (2.1, 1.1–4.2, PLog-rank = 2.2 × 10–2). The qRT-PCR based S315-score performed similarly to the S397-score, and was significantly associated with CSS in our extended cohort of 108 patients (5.0, 2.1–11.7, PLog-rank = 5.1 × 10–5) including metastatic (9.3, 1.8–50.0, PLog-rank = 2.3 × 10–3) and non-metastatic patients (4.4, 1.2–16.3, PLog-rank = 1.6 × 10–2), even in multivariate Cox regression, including clinicopathological parameters (7.3, 2.5–21.5, PWald = 3.3 × 10–4). Matched primary tumors and metastases revealed similar S315-scores, thus allowing prediction of outcome from metastatic tissue. The molecular-based qRT-PCR S315-score significantly improved prediction of CSS by the established clinicopathological-based SSIGN score (P = 1.6 × 10–3).ConclusionThe S3-score offers a new clinical avenue for ccRCC risk stratification in the non-metastatic, metastatic, and sunitinib-treated setting.

Background: Metastasis is the fatal character of cancer, leading to mortality of gastric cancer. In recent years, exosomes have been reported as extracellular vesicles secreted by cells. They contain various biological molecules including miRNAs from the original cells. Exosomal miRNAs are significant for pre-metastatic niche formation, as they can change the microenvironment and make it favorable for future metastasis. Therefore, the aim of this study was to identify dysregulated exosomal miRNAs as circulating biomarkers for prediction of metastasis of gastric cancer. Materials and Methods: Pre-treatment serum samples of 36 metastatic patients and 55 non-metastatic patients with stage II/III gastric cancer were collected. Exosomes were extracted and validated by western blot, transmission electron microscope and nanoparticle tracking analysis. MiRCURY LNATM miRNA miRNome PCR Array (containing 752 miRNAs) was performed in three pairs of serum exosomes. Each pair samples were with the same stage, race, gender and similar age. These three pairs of samples represented stage II, IIIA or IIIB gastric cancer, respectively. A panel of commonly dysregulated exosomal miRNAs was released from the PCR Array. Expressions of exosomal miRNAs were validated in the remaining 33 metastatic and 52 non-metastatic patients by RT-qPCR, as well as in gastric cancer cell culture medium and cell lines. Results: By comparing the expressions of exosomal miRNAs between the metastatic patients and matched non-metastatic ones, 13 upregulated and 6 downregulated miRNAs were released after normalization with miR-16-5p and miR-93-5p. Among these miRNAs, 7 of them were selected for further validation according to their fold changes, p-values and association with cancer development. MiR-379-5p and miR-410-3p were validated to be significantly upregulated in metastatic patients (P&amp;lt;0.01). Sensitivity, specificity and AUC were 67.31%, 69.70% and 0.6894 for miR-379-5p, and 65.38%, 66.67% and 0.6719 for miR-410-3p. Higher expression of serum exosomal miR-379-5p or miR-410-3p showed shorter overall survival of the patients (P&amp;lt;0.05). It was also found that miR-379-5p and miR-410-3p expressed significantly higher in gastric cancer cell culture medium comparing with gastric cancer cells. Conclusions: Exosomal miRNAs are dysregulated in the serum of metastatic gastric cancer patients before they are clinically diagnosed. Upregulation of serum exosomal miR-379-5p and/or miR-410-3p are promising circulating biomarkers for prediction of metastasis in stage II/III gastric cancer. Citation Format: Xin Liu, Kent-Man Chu. Exosomal miRNAs as circulating biomarkers for prediction of metastasis in stage II/III gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2765.

Background: Psychosocial difficulties occur in patients with breast cancer for many reasons including long-term treatments, organ loss, or deformity. Accordingly, we aimed to compare differences in distress tolerance levels between metastatic and non-metastatic female patients diagnosed with breast cancer and receiving chemotherapy. We also evaluated the possible relationship between distress tolerance levels and with background and clinical characteristics of the patients. Methods: 208 eligible female patients with breast cancer who received at least three chemotherapy sessions were included in our study. According to the presence of metastasis, the patients were divided into two groups those receiving palliative (metastatic, n=126) and adjuvant (non-metastatic, n=82) chemotherapy. Besides the study-specific data form, the Distress Tolerance Scale (DTS) was applied to patients to assess distress tolerance levels. Results: The age of participants was statistically significant between the non-metastatic and metastatic patients(p

BackgroundInflammation is one of the major hallmarks of cancer. This study was designed to profile a panel of inflammatory mediators in gastric adenocarcinoma (GA) and to identify their potential differences separately in metastatic and non-metastatic patient subgroups.MethodsSerum samples from 216 GA patients and 333 healthy controls from China were analyzed for six proteins using the Luminex multiplex assay.ResultsThe serum levels for all the six proteins were significantly elevated in metastatic GA compared to non-metastatic GA. Two acute phase proteins (SAA and CRP) and a CXC chemokine (GRO) were significantly elevated in metastatic GA (p <0.01) but smaller changes were observed in non-metastatic GA compared to healthy controls. OPN is moderately increased in non-metastatic GA (2.05-fold) and more severely elevated in metastatic GA (3.34-fold). Surprisingly, soluble VCAM1 and AGP were significantly lower in both non-metastatic and metastatic GA patients compared to controls. Several individual proteins were shown to possess moderate diagnostic value for non-metastatic GA (AUC = 0.786, 0.833, 0.823 for OPN, sVCAM1 and AGP, respectively) and metastatic GA (AUC = 0.931, 0.720, 0.834 and 0.737 for OPN, sVCAM1, SAA and CRP, respectively). However, protein combinations further improve the diagnostic potential for both non-metastatic GA (best AUC = 0.946) and metastatic GA (best AUC = 0.963). The protein combination with best AUC value for both comparisons is OPN+sVCAM1+AGP+SAA.ConclusionsThese results suggest that several serum proteins are directly related to the severity of gastric cancer. Overall, stronger associations are observed with metastatic than non-metastatic GA as the protein changes are greater with the metastatic status. A combination of these serum proteins may serve as non-invasive markers to assess the severity status and stage of gastric cancer.

Considering the importance of the canine cancer model of human disease, as well as the need for strategies for canine cancer management, the properties of exosomes are an emerging topic in canine oncology. In our study, exosomal RNA was isolated and investigated by next-generation sequencing. We identified several differentially expressed microRNAs (miRNAs/miRs) in the exosomes of two melanoma cell lines compared with non-tumor reference exosomes. We explored these potential melanoma-specific exosomal miRNAs further and found that miR-143 and let-7b increased in primary, whereas miR-210, 708, 221, and 222 increased in metastatic site originated melanoma cells. Further analysis showed miR-143 and 221 significantly increased in plasma exosomes of metastatic melanoma patients. Moreover, the sensitivity and specificity are >85% for differentiating the non-metastatic and metastatic patients. Therefore, these miRNAs can be an incredible biomarker candidate to identify metastatic melanoma and facilitate a better prognosis.

Simple SummaryBlood-based B-cell activating factor (BAFF), growth differentiation factor-15 (GDF-15) and osteopontin (OPN) have been reported to be biomarkers for the uveal melanoma (UM) metastases. This work intended to assess their kinetics and to evaluate their significance as a three-marker panel for clinical practice. Our results not only provided their cutoff values for differentiating the metastatic patients from non-metastatic patients, but also confirmed that the three-marker panel outperformed any single biomarker in distinguishing metastatic patients. Besides, the increasing trends of the levels of three biomarkers were detected in the two-year period before the imaging diagnosis of metastases. The multiplex panel of BAFF, GDF-15 and OPN might be a utilizable implementation for the detection of UM metastases. Since it is a retrospective pilot work, more well-designed prospective studies employing larger cohorts are still needed to validate the findings.Blood-based B-cell activating factor (BAFF), growth differentiation factor-15 (GDF-15) and osteopontin (OPN) have been identified to be promising biomarkers for the metastases of uveal melanoma (UM). This study intended to assess their kinetics and to evaluate their significance as a three-marker panel. A group of 36 UM patients with and 137 patients without metastases were included in the study. Their plasma OPN levels were measured by ELISA; serum BAFF and GDF-15 levels were determined with a Luminex MAGPIX system. Receiver operating characteristic (ROC) analysis was performed to calculate the cutoff values of the three markers for identifying the patients with metastases. The ability to identify patients with metastases was compared between the single markers and the combination as a three-marker panel. By using the Student’s t-test, we also investigated the kinetic changes of the levels of BAFF, GDF-15 and OPN across six periods (i.e., 0–6 months, 6–12 months, 12–18 months, 18–24 months, >24 months and post-metastasis) before the imaging diagnosis of metastases. By maximizing the Youden’s index, the serum GDF-15 level of 1209 pg/mL and the plasma OPN level of 92 ng/mL were identified to have the best performance for distinguishing the metastatic patients from non-metastatic patients. The three-marker panel offered a better performance in distinguishing patients with metastases, with an area under the curve of 0.802, than any single biomarker. Increasing trends of the levels of three biomarkers were observed in the two-year period before the imaging diagnosis of metastases. The combined panel of BAFF, GDF-15 and OPN might be a utilizable implementation for the detection of UM metastases. In the bioinformatics study with two external datasets, the high expression of gene BAFF and GDF-15 in primary UM tissues was identified to be associated with poor overall survival rates. As the current work is a single-center retrospective study, more well-designed prospective investigations employing larger cohorts are urgently needed to validate our findings.

Malnutrition affects up to 75% of cancer patients and results from a combination of anorexia and metabolic dysregulation. Metabolic and nutritional abnormalities in cancer patients can lead to cachexia, a multifactorial syndrome characterized by involuntary loss of skeletal muscle mass, systemic inflammation and increased protein catabolism. Cancer cachexia negatively affects patients' outcomes, response to anticancer treatments, quality of life, and survival. However, risk of malnutrition, and cachexia are still under-recognized in cancer patients. The Prevalence of Malnutrition in Oncology (PreMiO) study revealed that 51% of patients already had nutritional deficiencies at their first medical oncology visit. Here, we report the results of the subsequent retrospective, observational NUTRItional status at first medical oncology visit ON Clinical Outcomes (NUTRIONCO) study, aimed at assessing the impact of baseline nutritional and non-nutritional variables collected in the PreMiO study on the clinical outcomes of the same patients followed up from August 2019 to October 2021. We have highlighted a statistically significant association between baseline variables and patient death, rehospitalization, treatment toxicity, and disease progression at follow-up. We found a higher overall survival probability in the well-nourished general study population vs. malnourished patients (p < 0.001). Of major interest is the fact that patient stratification revealed that malnutrition decreased survival probability in non-metastatic patients but not in metastatic patients (p < 0.001). Multivariate analysis confirmed that baseline malnutrition (p = 0.004) and VAS score for appetite loss (p = 0.0104), in addition to albumin < 35 g/L (p < 0.0001) and neutrophil/lymphocyte ratio > 3 (p = 0.0007), were independently associated with the death of non-metastatic patients at follow-up. These findings highlight the importance of proactive, early management of malnutrition and cachexia in cancer patients, and in particular, in non-metastatic patients, from the perspective of a substantial improvement of their clinical outcomes.

Osteosarcomas are the most common solid malignancies of bone. In the last two decades there have been no concrete developments in their systemic treatment. In this trial we aimed to present our osteosarcoma patient clinical and demographic outcomes. Patients treated and followed up for osteosarcoma in Ankara Numune Education and Research Hospital from 2002 to 2012 were reviewed retrospectively. A total of 21 patients (15 male, 6 female) were diagnosed with osteosarcoma. The disease was located at extremities in 76% and in 14% was metastatic at the time of diagnosis. Median disease free survival (DFS) was 36 months in non-metastatic patients and median progression free survival (PFS) was 2 months in metastatic patients (p<0.0001). Median overall survival (OS) was 80 months and 4 months, respectively (p=0.012). There were no survival differences in terms of presentation with pathological fracture, tumor size, tumor grade, alkaline phosphatase and lactate dehydrogenase level and type of chemotherapy regimen. Tumor site and stages are the most important prognostic factors for osteosarcoma. Extremity primary tumors have beter survival rates than non-extremity tumors. As a result of the use of effective chemotherapy the long term survival rates have improved from 10-20% to 60-70% in the last decades but we need more active agents, especially for metastatic cases.

While B-cell activating factor (BAFF) was identified to promote the invasion in other malignancies, its role in the progression of uveal melanoma (UM) still remains unexplored. Here, we analysed the serum level of BAFF in UM patients with regard to its significance as biomarker for the metastases. In this retrospective study, serum BAFF levels in 173 UM patients (36 with metastases and 137 without), and 23 healthy controls were measured with a multiplexed sandwich ELISA system and then correlated with clinicopathological characteristics such as primary tumor size, tumor location, histological cell type, sex, cancer stage, cytogenetic alterations of chromosome 3, and the metastatic burden. Immunohistochemical staining of 50 UM tissue specimens was also performed to evaluate the expression of BAFF and its receptors BAFF-R and TACI. The metastatic patients were identified to have significantly higher serum BAFF levels (mean ± SD, 1520.8 ± 1182.1pg/ml) than those without metastases (950.4 ± 494.6pg/ml) and controls (810.3 ± 140.5pg/ml). While no distinctions were detected with regard to tumor location, histological cell type, gender, and monosomy 3, the patients in cancer stages II, III, and IV displayed higher serum BAFF levels than those in stage I. The serum BAFF level was significantly correlated with the metastatic burden. The serum BAFF level of 1120pg/ml was identified to have the best performance for distinguishing the metastatic patients from non-metastatic patients. In the kinetic study, we noticed that 20.8% of the analysed patients already demonstrated elevated serum BAFF concentrations before the clinical diagnosis of metastases. Positive BAFF staining was detected in the cytoplasm of single tumor cells (in 13 specimens), macrophages (in 12 specimens), and tumor-infiltrating lymphocytes (TILs) (in 13 specimens). The expressions of BAFF-R and TACI were also observed in 17 and 36 of the 50 tested UM specimens, respectively. Our study first suggests that BAFF might be a promising serum marker for the detection of UM metastases.

Geriatric patients account for nearly half of new colorectal cancer (CRC) cases. This study compares clinicopathological features, treatments, outcomes, and frailty in elderly (≥ 70) and younger (< 70) CRC patients at our center. Patients diagnosed with non-metastatic or de novo metastatic CRC between January 2015 and April 2024 were included. Demographic, pathological, and survival data were retrospectively collected. Analyses were performed using SPSS version 25, with statistical significance set at P < 0.05. Of the 414 non-metastatic CRC patients, 26.6% were aged ≥ 70. Elderly patients received less perioperative chemotherapy (60% vs. 81.6%, P < 0.001) and had more dose reductions (41.6% vs. 19.2%, P < 0.001). Frailty reduced perioperative chemotherapy in elderly non-metastatic patients (54.5% vs. 92.1%, P < 0.001) but did not affect dose reduction (37.9% vs. 33.3%, P = 0.764) or treatment duration (median 24weeks for both groups, P = 0.909). In metastatic patients, frailty shortened chemotherapy duration (9.5 vs. 15.5weeks, P = 0.129). Elderly patients had lower 5- and 8-year overall survival (OS) rates (64.7%, 60.1% vs. 83.0%, 78.8%, P = 0.004). In the de novo metastatic cohort (135 patients), age did not affect OS (19.4 vs. 17.3months, P = 0.590) or PFS (9.8 vs. 7.5months, P = 0.209). Rectal cancer (HR: 2.751, P = 0.005) and early chemotherapy termination (HR: 4.138, P < 0.001) worsened OS in non-metastatic CRC, while absence of RAS (HR: 2.043, P = 0.047), BRAF mutations (HR: 8.263, P = 0.010), and metastasectomy (HR: 3.650, P = 0.036) improved OS in metastatic CRC. Age does not independently worsen CRC survival, though early chemotherapy discontinuation impacts outcomes. Reduced-dose chemotherapy or monotherapy can help minimize adverse effects in elderly patients.

e21039 Background: Prognosis of early stage lung adenocarcinoma after surgery are usually affected by whether the patients had lymph node metastasis along with the primary lesions. The pathological stage of operable lung adenocarcinoma without or with lymph node metastasis were ⅠA/B or ⅡB/ⅢA, respectively, which related to different clinical outcomes, especially 5 years survivors (90% vs 50%). Due to the high tumor heterogeneity, it is difficult to trace which genes lead to tumor metastasis. We hypothesis that the genetic mutations in the smaller tumor might discover the key genetic changes associated with metastasis. Methods: 47 NSCLC patients with the primary lesion diameter less than or equal to 3cm were enrolled for genotyping with multiple cancer-related genes. Among them, 20 were lymph node metastasis and 27 were non-metastasis. Fisher test was used to analyze the difference between the two primary tumors. Results: EGFR amplification in all patients with lymph node metastasis is higher than the non-metastasis group (0.250 vs 0.037, P = 0.043), shown in the following table. This tendency was also found when the tumor diameter thresholds were configurated as &lt; 2.5cm and &lt; 2cm, even more prominently in the latter, (0.400 vs 0, P = 0.020). The CNV value of EGFR increased while the tumor diameter threshold value decreased. The difference of EGFR VAF between the two groups showed the same pattern. The metastatic patients had higher VAF values than the non-metastatic patients (each P-value was lower than 0.05). Conclusions: Based on the above results, it is speculated that EGFR mutations plays an important role in tumor early metastasis, and the genetic mutations in the smaller tumor might discover the key genetic changes associated with metastasis more notably. [Table: see text]

We describe clinical features and prognostic factors of renal medullary carcinoma (RMC) by performing a pooled analysis of all reported cases since 1995. A systematic search was performed to identify all articles describing patients with medullary renal cancer until February 2013. Survivals were estimated using Kaplan-Meier method with 95% confidence intervals and compared across the groups using the log-rank test. The following factors were evaluated using the Cox proportional hazards model: association of extension of disease at diagnosis, response to therapy, and surgical treatment of primary tumour with overall. A total 47 articles were selected; these described 165 patients with RMC plus 1 from our centre. The median age was 21 years and 98% of cases had the sickle cell trait. The mean size of the primary tumours was 6.0 cm, with an involvement of loco-regional lymph nodes in 71% of cases. The overall survival at diagnosis was 4.0 months in metastatic patients and 17.0 months in non-metastatic patients. Patients who received platinum-paclitaxel-gemcitabine had longer control of the disease when compared to topoisomerase inhibitors or targeted therapies. The multivariate analysis confirmed that the advanced stage at diagnosis increased the risk of death of about threefold. RMC is a tumour with poorer prognosis; based on these results, platinum-based chemotherapy is the preferred systemic treatment. Even if radical nephrectomy as an up-front strategy did not report a survival benefit, it may be considered to palliate local symptoms and to perform a correct diagnosis.

Background: Breast cancer remains a leading cause of cancer-related morbidity and mortality worldwide. Emerging evidence suggests that a subpopulation of circulating tumor cells—circulating cancer stem cells (cCSCs)—plays a pivotal role in metastasis, therapy resistance, and disease relapse. However, functional assessment of these cells in a minimally invasive manner poses a significant clinical challenge. Tumorsphere assays offer a unique in vitro platform to enrich and evaluate the self-renewal capacity of cCSCs, potentially reflecting the biological aggressiveness of the tumor. Establishing a reliable method for cultivating tumorspheres from peripheral blood may provide a novel biomarker for monitoring tumor progression and facilitating patient stratification. Materials and Methods: A total of 98 breast cancer patients, representing stages I to IV, were enrolled in this study. Peripheral blood samples were collected from each patient to detect cCSCs using the stemtrac® method, followed by a standardized tumorsphere-forming assay. Results: Tumorsphere count showed a significant correlation with disease stage and metastatic status. Patients with stage IV disease exhibited a higher median tumorsphere count compared to those with stage I (30 vs. 10; p &amp;lt; 0.002). Metastatic patients had more tumorspheres than non-metastatic patients (30 vs. 15; p &amp;lt; 0.005), with the highest counts observed in cases with multiple metastases (median 61; p &amp;lt; 0.001). Additionally, higher tumorsphere counts were associated with features of tumor aggressiveness, including HER2/neu positivity (35 vs. 10; p &amp;lt; 0.05), increased Ki-67 index, and higher histological grade Conclusion: These findings underscore the clinical relevance of tumorsphere assays as a minimally invasive method for monitoring tumor biology. The number of tumorspheres derived from peripheral blood may serve as a surrogate biomarker for disease progression, metastatic potential, and tumor aggressiveness, offering promising implications for real-time patient stratification and personalized treatment planning in breast cancer. Citation Format: M. PizonD. SchottK. Pachmann. Tumorsphere Formation as a Liquid Biopsy Biomarker of Tumor Aggressiveness and Metastatic Burden in Breast [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-03-01.