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

Abstract

Background Circulating tumor cells (CTCs) can be identified in approximately 25% of non-metastatic breast cancer patients (BC), and data are emerging regarding their prognostic significance. We hypothesized that CTCs identified prior to resection of the primary tumor would predict worse outcome in non-metastatic BC patients. Study Design We performed CTC enumerations on 509 patients with non-metastatic BC as part of an IRB approved study. CTCs (per 7.5 ml blood) were identified using the Cell Search® System (Janssen). The presence of ≥ 1 CTC meeting morphological 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. Results Median follow-up was 48 months and mean age was 53 years. Fifty-nine percent of patients (299/509) had tumors >2cm, and 46% (234/509) had positive lymph nodes. One hundred sixty-six patients received neoadjuvant chemotherapy (NACT) prior to CTC assessment, and 343 patients were chemonaïve. One or more CTC was identified in 43/166 (26%) of NACT treated patients, and in 81/343 (24%) of chemonaïve patients. CTCs were not associated with tumor size, grade, or lymph node status (P= NS). Detection of one or more CTCs predicted decreased relapse-free (log-rank P<0.001, 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. Conclusions One or more CTCs identified prior to resection of the primary breast tumor predicted worse relapse-free and overall survival, irrespective of primary tumor size, grade, or lymph node positivity.

Perioperative circulating tumor cells (CTCs) and CTC-white blood cells detected by a size-based platform predict worse prognosis in renal cell cancer patients

“…In the present study, we firstly demonstrated total CTCs, mesenchymal CTCs and CTC-WBC before or after surgery showed little association with clinical characteristics in T 1-3 N0M0 renal cancer patients. In non-metastasis breast cancer, the preoperative CTCs were also poorly associated with tumor size, grade or lymph node status [26].…”

Precision Medicine and the Role of Biomarkers of Radiotherapy Response in Breast Cancer

“…CTCs and circulating tumor DNA are cells or DNA that have been shed by the tumor into the systemic circulation; these can be indicators of residual disease following treatment and are likely to represent an important mechanism through which a tumor can metastasise (123,124). CTCs have been detected in up to 30% of non-metastatic BC patients and their presence (even just one CTC) has been shown to be prognostic for recurrence-free survival and overall survival (125)(126)(127)(128)(129)(130)(131)(132)(133)(134)(135). CTC detection is also related to metastasis and poor survival in lowrisk patients with lymph node negative disease who did not receive adjuvant therapy (133).…”

Methylation profiling in promoter sequences of ATM and CDKN2A (p14ARF/p16INK4a) genes in blood and cfDNA from women with impalpable breast lesions

“…In this battle between immune system and tumor, many apoptotic and necrotic tumor cells are phagocytized, increasing the concentration of cell-free DNA (cfDNA) in the blood which can be used as liquid biopsy. In some cases, this process starts very early, even in the absence of the primary site formed (10)(11)(12)(13). In this context, in the course of carcinogenesis and invasion of tumor cells in the bloodstream, white blood cells (WBC) are constantly undergoing molecular alterations.…”