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Prognostic Value of Circulating Tumor Cells Identified Before Surgical Resection in Nonmetastatic Breast Cancer Patients.

ABSTRACT: Circulating tumor cells (CTCs) can be identified in approximately 25% of nonmetastatic breast cancer patients, and data are emerging regarding their prognostic significance. We hypothesized that CTCs identified before resection of the primary tumor would predict worse outcomes in nonmetastatic breast cancer patients.We performed CTC enumerations on 509 patients with nonmetastatic breast cancer as part of an IRB-approved study. The CTCs (per 7.5 mL blood) were identified using the CellSearch System (Janssen). The presence of ?1 CTC meeting morphologic criteria for malignancy was considered a positive result. Log-rank test and Cox regression analysis were applied to establish the association of CTCs with relapse-free and overall survival.Median follow-up was 48 months and mean age was 53 years. Fifty-nine percent of patients (299 of 509) had tumors larger than 2 cm, and 46% (234 of 509) had positive lymph nodes. One hundred sixty-six patients received neoadjuvant chemotherapy (NACT) before CTC assessment, and 343 patients were chemonaïve. One or more CTC was identified in 43 of 166 (26%) NACT treated patients, and in 81 of 343 (24%) chemonaïve patients. Circulating tumor cells were not associated with tumor size, grade, or lymph node status (p = NS). Detection of 1 or more CTCs predicted decreased relapse-free (log-rank p < 0.001, hazard ratio [HR] 2.72, 95% CI 1.57 to 4.72; p < 0.001) and overall survival (log-rank p = 0.02, HR 2.29, 95% CI 1.12 to 4.67; p = 0.03) at 48 months of follow-up.One or more CTCs identified before resection of the primary breast tumor predicted worse relapse-free and overall survival, irrespective of primary tumor size, grade, or lymph node positivity.

SUBMITTER: Hall CS

PROVIDER: S-EPMC5868486 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Prognostic Value of Circulating Tumor Cells Identified Before Surgical Resection in Nonmetastatic Breast Cancer Patients.

Hall Carolyn S CS Karhade Mandar G MG Bowman Bauldry Jessica B JB Valad Lily M LM Kuerer Henry M HM DeSnyder Sarah M SM Lucci Anthony A

Journal of the American College of Surgeons 20160308 1

<h4>Background</h4>Circulating tumor cells (CTCs) can be identified in approximately 25% of nonmetastatic breast cancer patients, and data are emerging regarding their prognostic significance. We hypothesized that CTCs identified before resection of the primary tumor would predict worse outcomes in nonmetastatic breast cancer patients.<h4>Study design</h4>We performed CTC enumerations on 509 patients with nonmetastatic breast cancer as part of an IRB-approved study. The CTCs (per 7.5 mL blood) w ...[more]

PMID: 27049782

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Project description:ImportanceFor patients with resected, nonmetastatic colorectal cancer (CRC), the optimal surveillance protocol remains unclear.ObjectiveTo evaluate whether serial circulating tumor DNA (ctDNA) levels detected disease recurrence earlier, compared with conventional postoperative surveillance, in patients with resected CRC.Design, setting, and participantsThis study included patients (n = 58) with stage I, II, or III CRC who underwent radical surgical resection at 4 Swedish hospitals from February 2, 2007, to May 8, 2013. Eighteen patients received adjuvant chemotherapy at the discretion of their clinicians, who were blinded to the ctDNA results. Blood samples were collected at 1 month after the surgical procedure and every 3 to 6 months thereafter for ctDNA analysis. Patients were followed up until metachronous metastases were detected, or for a median of 49 months. Data analysis was performed from March 1, 2009, to June 23, 2018.Main outcomes and measuresSensitivity and timing of ctDNA positivity were compared with those of conventional surveillance modalities (computed tomographic scans and serum carcinoembryonic antigen tests) for the detection of disease recurrence.ResultsThis study included 319 blood samples from 58 patients, with a median (range) age of 69 (47-83) years and 34 males (59%). The recurrence rate among patients with positive ctDNA levels was 77% (10 of 13 patients). Positive ctDNA preceded radiologic and clinical evidence of recurrence by a median of 3 months. Of the 45 patients with negative ctDNA throughout follow-up, none (0%; 95% CI, 0%-7.9%) experienced a relapse, with a median follow-up of 49 months. However, 3 (6%; 95% CI, 1.3%-17%) of the 48 patients without relapse had a positive ctDNA result, which subsequently fell to undetectable levels during follow-up.Conclusion and relevanceAlthough these findings need to be validated in a larger, prospective trial, they suggest that ctDNA analysis could complement conventional surveillance strategies as a triage test to stratify patients with resected CRC on the basis of risk of disease recurrence.

Project description:BackgroundCirculating angiogenic cytokines (CACs) have been confirmed as prognostic biomarkers and therapeutic targets in several solid tumors. However, their role as prognostic biomarkers in resected pancreatic ductal adenocarcinoma (PDAC) is unknown.ResultsThe expression of CACs in patients with PDAC differs from those with CP both pre- and postoperatively. Correlation analyses show significant correlations between circulating levels of CACs: VEGF was correlated with IL-6 (r = 0.457), FGF (r = 0.44), G-CSF (r = 0.543), HGF (r = 0.586) and SDF-1α (r = 0.784) before the surgery. The circulating levels of TNF-α correlated with the serum concentration of IL-4 before (r= 0.656) and after the resection (r = 0.776 on POD 3, r = 0.865 on POD 7). Gender did not show any correlation with serum levels of CAC, except for significantly higher levels of EGF in males (P = 0.002). Other clinicopathological variables such as age (< 65 vs. > 65 years), T, N, or UICC stage did not have an association with the cytokine levels. The multivariate model including the entire angiogenic panel revealed that postoperative increasing levels of EGF (P = 0.023), PDGFA-A (P = 0.024), TNF-α (P = 0.001) and IL-8 (P = 0.049) were associated with a favorable prognosis, whereas elevating levels of VEGF (P = 0.005) correlated with a poor cancer-specific survival.Materials and methodsPreoperative and postoperative blood samples were collected in patients undergoing surgery for PDAC (n = 40) or chronic pancreatitis (CP; n = 9). Serum levels of 13 angiogenic cytokines (IL-4, IL-6, FGF-b, G-CSF, TNF-α, VEGF, HGF, SDF-1α, IL-8, EGF, Ang-1, PDGF-AA and PlGF) were analyzed using ELISA and Multiplex. Prognostic factors were identified by a Cox proportional hazards model.ConclusionsPostoperative changes of serum levels of certain angiogenic cytokines correlate with patients' prognosis after resection for pancreatic cancer. CACs should thus be considered as biomarkers in patients with resected pancreatic cancer.

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Prognostic Value of Circulating Tumor Cells Identified Before Surgical Resection in Nonmetastatic Breast Cancer Patients.

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Prognostic Value of Circulating Tumor Cells Identified Before Surgical Resection in Nonmetastatic Breast Cancer Patients.

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