Introduction Circulating tumor cells (CTCs) are an independent prognostic factor for progression-free survival (PFS) and overall survival (OS) in patients with metastatic breast cancer. found to be superior to that of tumor burden as measured by Swenerton score or by serum tumor markers, ascribing a peculiar biological value to CTCs. These observations also raised the possibility that CTCs might represent a population of tumorigenic cancer cells with stem cell properties that might play an important role in tumor dissemination [22,23]. Previously, we showed that among patients with metastatic breast cancer (MBC) treated with first or subsequent lines of chemotherapy, patients with metastatic IBC had lower CTC counts than did patients with non-inflammatory metastatic breast cancer (non-IBC) [24]. We also showed, for patients with metastatic IBC, that differences in OS between patients with fewer than five CTCs and others with five or more CTCs were not statistically significant; hence, the prognostic value of a CTC count in patients with pretreated metastatic IBC is limited [24]. The prognostic value of a CTC count in newly diagnosed IBC has not been established. In the present study, we investigated the prognostic value of a baseline CTC count and the relation between a baseline CTC count and primary tumor characteristics in TAK-875 patients with newly SFN diagnosed IBC. Recent data suggest that statins might have anticancer effect in IBC, and their use was associated with prolonged PFS in primary IBC [25]. Therefore, we performed exploratory analysis to evaluate the relation between exposure to statin before diagnosis of IBC and CTC count. Methods Study patients This retrospective study was conducted under Institutional Review Board (IRB)-approved protocol DR10-0227 by using the Clinic Station, the MD Anderson Cancer Center (MDACC) electronic medical record database. Patients were identified by using two databases; database of newly diagnosed IBC patients treated in MD Anderson Cancer Center between 1989 and 2011, as described in the previous study [3], and the MDACC IBC database with available data from 2007 to 2012 (Figure?1). A population of consecutive stage III IBC and metastatic IBC patients with CTCs measurement before starting neoadjuvant or first-line treatment, was eligible. Only treatment-na?ve patients with newly diagnosed disease, starting treatment with neoadjuvant or first-line chemotherapy, were included in this study. Patients underwent systemic therapy, as TAK-875 appropriate for their malignancies, irrespective of CTCs. Patients with concurrent malignancy other than nonmelanoma skin cancer in the previous 5?years were excluded. Figure 1 Patients flow. All patients underwent pretreatment diagnostic biopsy. The diagnosis of IBC was based on clinical signs TAK-875 such as diffuse erythema, [28]. In all patients, data regarding age, menopausal status, tumor histologic subtype, hormone-receptor status, HER2 amplification status, type and number of sites of metastases, delivery of systemic therapy, and outcome (progression, survival, pathological complete remission) were recorded and compared with the presence and number of CTCs. Because statins might have an antitumor effect in IBC, we also recorded statin use before the diagnosis of IBC [25]. Lipophilic statins (simvastatin, fluvastatin, and lovastatin) were classified as L-statins, and weakly lipophilic-to-hydrophilic statins (atorvastatin, pravastatin, and rosuvastatin) were classified as H-statins, as described previously [25]. The retrospective study was approved by the Institutional Review Board of the University of Texas, MD Anderson Cancer Center, and a waiver of consent form was granted. Detection of CTCs in peripheral blood The CellSearch system (Veridex Corporation, Warren, NJ, USA) was used to detect and enumerate CTCs in 7.5?ml of whole peripheral blood. Samples were subjected to enrichment of epithelial cells with anti-EpCAM-coated ferrous particles. CTCs were defined as nucleated cells (DAPI+) expressing cytoplasmic cytokeratins 8, 18, or 19 and lacking.