Group psychoeducation is an efficacious intervention to prevent recurrence in pharmacologically treated patients with bipolar I and II disorder.

The nuclear factor (NF)-kB system is a promising anticancer target due to its role in oncogenesis and chemoresistance in preclinical models. To provide evidence in a clinical setting on the role of NF-kB in breast cancer, we aimed to study the value of basal NF-kB/p65 in predicting resistance to neoadjuvant chemotherapy, and to characterise the pharmacodynamic changes in NF-kB/p65 expression following chemotherapy in patients with locally advanced breast cancer. Pre-and post-chemotherapy tumour specimens from 51 breast cancer patients treated with anthracycline-and/or taxane-containing neoadjuvant chemotherapy were assayed by immunohistochemistry for NF-kB/p65 subcellular expression. We studied NF-kB/p65, a wellcharacterised member of the NF-kB family that undergoes nuclear translocation when NF-kB is activated. Activation of NF-kB (i.e. nuclear NF-kB/p65 staining in pre-therapy specimens) was linked to chemoresistance. Patients with NF-kB/p65 nuclear staining in pre-treatment samples had a 20% clinical response rate, while patients with undetected nuclear staining had a 91% response rate to chemotherapy (P ¼ 0.002). Notably, four patients achieved a complete histological response and none of them had pre-treatment NF-kB/p65 nuclear staining. Moreover, the number of patients with NF-kB/p65 activation increased after chemotherapy exposure. It is concluded that NF-kB/p65 activation assayed by immunohistochemistry is a predictive factor of resistance to neoadjuvant chemotherapy in breast cancer patients. Moreover, NF-kB activation was inducible following chemotherapy in a proportion of breast cancer patients. These novel clinical findings strengthen the rationale for the use of NF-kB inhibitors to prevent or overcome chemoresistance in breast cancer.

IntroductionIncreasing evidence supports the view that the detection of circulating tumor cells (CTCs) predicts outcomes of nonmetastatic breast cancer patients. CTCs differ genetically from the primary tumor and may contribute to variations in prognosis and response to therapy. As we start to understand more about the biology of CTCs, we can begin to address how best to treat this form of disease.MethodsNinety-eight nonmetastatic breast cancer patients were included in this study. CTCs were isolated by immunomagnetic techniques using magnetic beads labelled with a multi-CK-specific antibody (CK3-11D5) and CTC detection through immunocytochemical methods. Estrogen receptor, progesterone receptor and epidermal growth factor receptor (EGFR) were evaluated by immunofluorescence experiments and HER2 and TOP2A by fluorescence in situ hybridization. We aimed to characterize this set of biomarkers in CTCs and correlate it with clinical-pathological characteristics.ResultsBaseline detection rate was 46.9% ≥ 1 CTC/30 ml threshold. CTC-positive cells were more frequent in HER2-negative tumors (p = 0.046). In patients younger than 50 years old, HER2-amplified and G1-G2 tumors had a higher possibility of being nondetectable CTCs. Heterogeneous expression of hormonal receptors (HRs) in samples from the same patients was found. Discordances between HR expression, HER2 and TOP2A status in CTCs and their primary tumor were found in the sequential blood samples. Less that 35% of patients switched their CTC status after receiving chemotherapy. EGFR-positive CTCs were associated with Luminal tumors (p = 0.03).ConclusionsThis is the largest exploratory CTC biomarker analysis in nonmetastatic BC patients. Our study suggests that CTC biomarkers profiles might be useful as a surrogate marker for therapeutic selection and monitoring since heterogeneity of the biomarker distribution in CTCs and the lack of correlation with the primary tumor biomarker status were found. Further exploration of the association between EGFR-positive CTCs and Luminal tumors is warranted.

A more aggressive molecular phenotype and high breast density were identified in breast tumors that truly arise in the interval between screenings.

CD133 has been associated with cell properties such as self renewal, migration and vasculogenic mimicry, potentially involved in generation of circulating tumor cells (CTCs). We characterized CD133 expression in CTCs of 98 nometastatic breast cancer (BC) patients. CTCs were isolated by immunomagnetic techniques using magnetic beads labeled with a multicytokeratin(CK)-specific antibody (CK3-11D5) and CTCs and CD133 detection through immunocytochemical methods. CK 1 /CD133 1 CTCs were identified in 65% of patients at baseline and 47.8% after systemic therapy (p 5 0.53). Correlation of CD133 status in CTCs with classical clinicopathological characteristics and response to therapy was performed. Her2 not amplified and low Ki-67 index were positively correlated with presence of CK 1 /CD133 1 CTCs. Before any treatment, CK 1 /CD133 1 CTCs were more frequently isolated in patients with luminal BC subtype. No statistically significant differences were found between proportion of CK 1 /CD133 1 CTCs and BC subtypes after systemic therapy, implying a relative enrichment of CK 1 /CD133 1 CTCs in triple negative and HER2-amplified tumors. While CK 1 /CTCs decreases after chemotherapy when analyzing the whole population, CK 1 / CD133 1 CTCs were enriched in post-treatment samples in nonluminal BC subtypes. These findings suggest the potential role of CD133 as a promising marker of chemoresistance in nonluminal BC patients. Further prospective studies and extensive preclinical modeling will be needed to confirm whether CD133 is a marker of resistance to chemotherapy, and its role as a target for novel anticancer therapies targeting cancer stem cells and tumor vasculature.Breast cancer (BC) is a complex and heterogeneous disease comprising multiple tumor entities associated with distinctive different biological feature, clinical behaviors and response to therapy. The current classification of BC is based on the pattern of expression of the hormone receptors (HR) estrogen receptor and/or progesterone receptor, and human epidermal receptor 2 (Her2) that identify three major BC subtypes: luminal tumors, which are HR positive and Her2 negative; Her2 amplified tumors; and those tumors with lack of expression of the three receptors, referred to as triple negative (TN) BC. 1 Despite advances in BC treatments, primary and acquired resistance to cancer therapies remains a challenge especially in nonmetastatic patients. Cancer stem cells (CSC) have been