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IntroductionCirculating tumor cells (CTCs) represent an independent predictor of outcome in patients with metastatic breast cancer (MBC). We assessed the prognostic impact of CTCs according to different first-line systemic treatments, and explored their potential predictive value in MBC patients.MethodsWe retrospectively evaluated 235 newly diagnosed MBC patients, treated at the University of Texas MD Anderson Cancer Center. All patients had a baseline CTC assessment performed with CellSearch®. Progression-free survival and overall survival were compared with the log-rank test between groups, according to CTC count (< 5 vs. ≥ 5) and type of systemic therapy. We further explored the predictive value of baseline CTCs in patients receiving different treatments.ResultsAt a median follow-up of 18 months, the CTC count was confirmed to be a robust prognostic marker in the overall population (median progression-free survival 12.0 and 7.0 months for patients with CTC < 5 and ≥ 5, respectively; P < 0.001). Conversely, in patients with human epidermal growth factor receptor-2-overexpressed/amplified tumors receiving trastuzumab or lapatinib, the baseline CTC count was not prognostic (median progression-free survival 14.5 months for patients with CTC < 5 and 16.1 months for those with CTC ≥ 5; P = 0.947). Furthermore, in patients with human epidermal growth factor receptor-2 normal tumors, a baseline CTC count ≥ 5 identified subjects who derived benefit from more aggressive treatments, including combination chemotherapy and chemotherapy plus bevacizumab.ConclusionsThis analysis suggests that the prognostic information provided by CTC count may be useful in patient stratifications and therapeutic selection, particularly in the group with positive CTCs, in which various therapeutic choices may procure differential palliative benefit.

In metastatic breast, prostate and other cancers more than 5 circulating tumor cells are often detected using the CellSearch System, and may correlate with prognosis. However, in the setting of localized prostate cancer the number of detectable circulating tumor cells was low, with findings comparable to those in men who were biopsy negative for cancer. We found no correlation between the number of circulating tumor cells and known prognostic factors in this population.

IntroductionTraditional factors currently used for prognostic stratification do not always adequately predict treatment response and disease evolution in advanced breast cancer patients. Therefore, the use of blood-based markers, such as circulating tumor cells (CTCs), represents a promising complementary strategy for disease monitoring. In this retrospective study, we explored the role of CTC counts as predictors of disease evolution in breast cancer patients with limited metastatic dissemination.MethodsA total of 492 advanced breast cancer patients who had a CTC count assessed by CellSearch prior to starting a new line of systemic therapy were eligible for this analysis. Using the threshold of 5 CTCs/7.5 ml of blood, pretreatment CTC counts were correlated in the overall population with metastatic site distribution, evaluated at baseline and at the time of treatment failure, using Fisher’s exact test. Time to visceral progression and time to the development of new metastatic lesions and sites were estimated in patients with nonvisceral metastases and with single-site metastatic disease, respectively, by the Kaplan-Meier method. Survival times were compared between groups according to pretreatment CTC count by logrank test.ResultsIn the overall population, a pretreatment level ≥5 CTCs/7.5 ml was associated with an increased baseline number of metastatic sites compared with <5 CTCs/7.5 ml (P = 0.0077). At the time of treatment failure, patients with ≥5 CTCs/7.5 ml more frequently developed new metastatic lesions and sites compared with those with <5 CTCs/7.5 ml (development of new lesions: P = 0.0002; development of new sites: P = 0.0031). Among patients with disease originally confined to nonvisceral sites, ≥5 CTCs/7.5 ml was associated with remarkably shorter time to visceral metastases (P = 0.0021) and overall survival (P = 0.0006) compared with <5 CTCs/7.5 ml. In patients with single-site metastatic disease, ≥5 CTCs/7.5 ml was associated with a significant reduction of the time to development of new metastatic sites (P = 0.0051) and new lesions (P = 0.0002) and with worse overall survival (P = 0.0101).ConclusionOur results suggest that baseline CTC counts can be used as an early predictor of metastatic potential in breast cancer patients with limited metastatic dissemination.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-014-0440-8) contains supplementary material, which is available to authorized users.

In this large retrospective study, CTCs were strongly predictive of survival in all MBC subtypes except HER2+ patients who had been treated with targeted therapy. Our results clearly demonstrate the value of enumerating CTCs in MBC and strongly suggest an interesting biological implication in the HER2+ subset of patients that need to be further explored.

Detection of five or more CTCs during therapeutic monitoring can accurately predict prognosis in MBC beyond metabolic response. FDG-PET/CT deserves a role in patients who have fewer than five CTCs at midtherapy. Prospective trials should evaluate the most sensitive and cost-effective modality for therapeutic monitoring in MBC.

A single hsTnT level less than 6 ng/L was associated with a markedly decreased risk of AMI, while serial levels at 19 ng/L or less identified patients at less than 1% risk of 30-day ACE.

Circulating tumor cells (CTC) are an independent prognostic factor in metastatic breast cancer patients (MBC). However, CTC are undetectable in one third of patients. The aim of this study was to assess the prognostic factors in MBC patients without detectable CTC. This retrospective study included 292 MBC patients evaluated between January 2004 and December 2007. CTC were enumerated before patients started a new line of treatment using the CellSearch TM . Overall survival (OS) was calculated from the date of CTC measurement and estimated by the Kaplan-Meier product limit method. CTC were not detected in 35.96% patients, whereas 40.75% patients had CTC 5. Undetectable CTC status was positively correlated with presence of brain metastasis (OR: 6.17, 95%CI 5 2.14-17.79; p 5 0.001), and inversely correlated with bone metastasis (OR: 0.47; 95%CI 5 0.27-0.80; p 5 0.01). In multivariate analysis, hormone receptors, number of metastatic sites and lines of therapy were independent prognostic factors for OS in patients without detectable CTC. Patients without detectable CTC before starting of a new line of therapy comprise a heterogeneous group with substantially different prognosis. We showed that some important metastatic disease characteristics are predictive of undetectable CTC status in MBC.Breast cancer is one of the most common malignancies in women with estimated 182,460 new cases diagnosed in 2008.1 Despite advances in prevention, detection and adjuvant therapy of breast cancer, substantial proportions of patients are diagnosed or further develop metastatic disease. Metastatic breast cancer (MBC) patients represent a heterogeneous group whose prognosis depends on different tumor and host related factors such as tumor hormone receptor status, HER-2 status, and tumor grade, extent of disease, age, performance status and previous therapy. 2-5Circulating tumor cells (CTC) are cancer cells of epithelial origin, whose detection using the CellSearch TM system (Veridex Corporation, Warren, NJ, USA) before and during treatment represents an independent predictor of progression-free survival (PFS) and overall survival (OS) in patients with MBC. 6,7 Superior survival among patients with CTC < 5 was observed regardless of histology, hormone receptor and HER-2/neu status, sites of first metastases, or whether the patient had recurrent or de novo metastatic disease. 6,8 The prognostic value of CTC was demonstrated to be superior to tumor burden as measured by Swenertone score (quantitative scoring system to estimate the total burden of metastatic disease as the sum of the scores for tumor extent at all known disease sites) 2 or by serum tumor markers, suggesting a special biological value of CTC. The prognostic value of CTC was shown to be superior to conventional and functional imaging procedures as well. 7,9 These data suggest the possibility that CTC might represent a population of tumorigenic cancer stem cells and might play an important role in tumor dissemination. 10,11 CTC are not detectable in 30-35% of MBC patients. ...