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The objective of this study is to define the survival outcomes associated with distinct molecular phenotypes defined by immunohistochemical staining of paraffin-embedded tissues among invasive breast cancer cases identified from the Nurses’ Health Study (NHS). Tissue microarrays were constructed from archived tissue blocks of women diagnosed with breast cancer in the NHS (1976–1997). Invasive non-metastatic breast cancer tumors (n = 1,945) were classified into 1 of 5 molecular phenotypes based on immunohistochemistry assays for estrogen receptor (ER), progesterone receptor (PR), HER2, cytokeratin (CK) 5/6, epidermal growth factor receptor (EGFR) and grade. Survival outcomes were estimated using the Kaplan–Meier product limit method. Cox-proportional hazards models were fitted to determine the association of molecular phenotype with survival outcomes after adjusting for covariates. 1,279 (65.8%) tumors were classified as luminal A, 279 (14.3%) as luminal B, 95 (4.9%) as HER2 type, 203 (10.4%) as basal-like and 89 (4.6%) tumors were unclassified. The 5-year breast cancer-specific survival estimates for women with luminal A, luminal B, HER2-type, basal-like and unclassified tumors were 96, 88, 81, 89 and 85%, respectively. In the multivariable model, compared to cases with luminal A tumors, cases with luminal B (HR 1.90, 95% CI 1.33–2.71), HER2-type (HR 1.36, 95% CI 0.87–2.12), basal-like (HR 1.58, 95% CI 1.05–2.39) and unclassified (HR 1.38, 95% CI 0.87–2.20) tumors had higher hazard of breast cancer death. Similar trends were observed for both overall and recurrence-free survival. In conclusion, compared to women who have luminal A tumors those with luminal B, HER2-type, basal-like and unclassified tumors had a worse prognosis, when tumor subtype was defined by immunohistochemistry. This method may provide a cost-effective means of determining prognosis in the clinical setting.

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. ...

BACKGROUND: Cancer is a risk factor for venous thromboembolism (VTE). Circulating tumour cells (CTCs) are an independent predictor of survival in metastatic breast cancer (MBC) patients. The aim of this study was to test the hypothesis that CTCs are associated with the risk of VTE in MBC patients. METHODS: This retrospective study included 290 MBC patients treated in the MD Anderson Cancer Center from January 2004 to December 2007. Circulating tumour cells were detected and enumerated using the CellSearch system before starting new lines of therapy. RESULTS: At a median follow-up of 12.5 months, 25 patients experienced VTE and 53 patients died without experiencing thrombosis. Cumulative incidence of thrombosis at 12 months was 8.5% (95% confidence interval (CI) ¼ 5.5%, 12.4%). Patients with CTCs X1 and X5 had a higher incidence of VTE compared with patients with 0 and o5 CTCs (12-month estimate, 11.7 and 11.6% vs 3 and 6.6%; P ¼ 0.006 and P ¼ 0.076, respectively). In the multivariate model, patients with CTCsX1 had a hazard ratio of VTE of 5.29 (95% CI ¼ 1.58, 17.7, P ¼ 0.007) compared with patients with no CTCs. CONCLUSION: These results suggest that CTCs in MBC patients are associated with increased risk of VTE. These patients should be followed up more closely for the risk of VTE.

IntroductionCirculating tumor cells (CTCs) are an independent prognostic factor for progression-free survival (PFS) and overall survival (OS) in patients with metastatic breast cancer. Inflammatory breast cancer (IBC) is one of the most aggressive forms of breast cancer. The prognostic value of a CTC count in newly diagnosed IBC has not been established. The aim of this study was to assess the prognostic value of a baseline CTC count in patients with newly diagnosed IBC.MethodsThis retrospective study included 147 patients with newly diagnosed IBC (77 with locally advanced and 70 with metastatic IBC) treated with neoadjuvant therapy or first-line chemotherapy during the period from January 2004 through December 2012 at The University of Texas MD Anderson Cancer Center. CTCs were detected and enumerated by using the CellSearch system before patients were started with chemotherapy.ResultsThe proportion of patients with ≥1 CTC was lower among patients with stage III than among patients with metastatic IBC (54.5% versus 84.3%; P = 0.0002); the proportion of patients with ≥5 CTCs was also lower for stage III than for metastatic IBC (19.5% versus 47.1%; P = 0.0004). Patients with fewer than five CTCs had significantly better progression-free survival (PFS) (hazard ratio (HR) = 0.60; P = 0.02) and overall survival (HR = 0.59; P = 0.03) than patients with five or more CTCs. Among patients with stage III IBC, there was a nonsignificant difference in PFS (HR = 0.66; 95% confidence interval (CI), 0.31 to 1.39; P = 0.29) and OS (HR = 0.54; 95% CI, 0.24 to 1.26; P = 0.48) in patients with no CTCs compared with patients with one or more CTCs. In multivariate analysis, CTC was prognostic for PFS and OS independent of clinical stage.ConclusionsCTCs can be detected in a large proportion of patients with newly diagnosed IBC and are a strong predictor of worse prognosis in patients with newly diagnosed IBC.