We investigated the prognostic significance of circulating tumor cells (CTCs) determined immediately before the second cycle of chemotherapy in patients with metastatic breast cancer (MBC). The CTC counts were taken at baseline, before the first cycle of chemotherapy (CTC-0), and on day 21 before commencing the second cycle of chemotherapy (CTC-21) in consecutive MBC patients. The study's primary objectives were to analyze relationships between CTC-21 count and overall survival (OS). Based on the current literature, the CTC measurements were dichotomized as 0 -4 versus Ն5 CTCs. Of 117 patients recruited, 99 were evaluable. Patients with 0 -4 CTCs on day 21 had a significantly better OS than those with Ն5 CTCs (median OS: 38.5 months vs. 8.7 months). They also had a significantly better progression-free survival (PFS; median: 9.4 months vs. 3.0 months) and clinical benefit rate (77% vs. 44%). The OS of patients whose baseline CTCs were Ն5 but dropped to Ͻ5 on day 21 was apparently similar to those who had Ͻ5 CTCs at baseline. In a Cox regression analysis, CTC-21 was the only independent variable significantly predicting OS and PFS. Our data indicate that CTCs determined immediately before the second cycle of chemotherapy is an early and strong predictor of treatment outcome in MBC patients. The Oncologist 2013;18:917-923 Implications for Practice: We investigate the prognostic significance of circulating tumor cells (CTCs) immediately before administering the second cycle of a chemotherapy regimen in patients with metastatic breast cancer. Patients with 0 -4 CTCs on day 21 (regardless the baseline CTC count) had a significantly better PFS and OS than those with Ն5 CTCs. In a Cox regression analysis, CTC-21 was the only independent variable significantly predicting OS (p ϭ .009) and PFS (p ϭ .047). Our study suggests that CTCs count determined immediately before the second cycle of chemotherapy is an early, and strong, predictor of treatment outcome in MBC patients, since it can identify those patients who derive little benefit from the chemotherapy regimen and also have a poor prognosis with conventional treatment. INTRODUCTIONThe detection and enumeration of circulating tumor cells (CTCs) in patients with metastatic breast cancer (MBC) is currently undergoing intense investigation. Several studies have shown that the number of CTCs at baseline is an independent predictor of progression-free survival (PFS) and overall survival (OS) in MBC patients [1][2][3][4]. The U.S. Food and Drug Administration has approved a semiautomated immunomagnetic method, the CellSearch system (Veridex, LLC, Warren, NJ, https://www.cellsearchctc.com/), specifically for this purpose. CTC enumeration using the CellSearch system appears to be a reproducible method. In a previous study, we did not observe any significant intrapatient variability in CTCs in two

A comprehensive family history is essential to identify patients at risk for hereditary cancer who could benefit from genetic counseling (GC). In a previous study, we observed a low occurrence of family history record (FHR) collection rate and GC referral among oncologists at our institution. The present work analyzes whether the implementation of a heredofamilial cancer unit (HFCU) would improve these parameters. We retrospectively compared the FHR rate in clinical records, National Cancer Institute (NCI) general criteria for hereditary cancer suspicion, GC referrals and FHR quality in two cohorts: cohort 1 (patients diagnosed before HFCU creation) and cohort 2 (after HFCU creation). Of 1,175 patients (590 cohort 1 and 585 cohort 2), FHRs were consigned in 27.3 % and 52.5 % of patients, respectively (p < 0.001). The GC referral of patients with any NCI criterion was 13.6 % xin cohort 1 vs. 40.5 % in cohort 2 (p < 0.001). FHR quality improved in terms of the total number of relatives (164 vs. 314, p = 0.1, N.S.) and number of healthy relatives consigned (80 vs. 191, p < 0.01). Nine mutations (6 BRCA, 1 MEN1, 2 Lynch), 4 unknown significance variants (all in BRCA) and 2 with no mutation were identified among patients referred from cohort 2. We conclude that the creation of a heredofamilial cancer unit has changed both FHR and GC referrals among oncologists at our institution, although continuous educational efforts are required.