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The Androgen Receptor (AR) is a potential prognostic marker and therapeutic target in breast cancer. We evaluated AR protein expression in high-risk breast cancer treated in the adjuvant setting. Tumors were subtyped into luminal (ER+/PgR±/AR±), molecular apocrine (MAC, [ER-/PgR-/AR+]) and hormone receptor negative carcinomas (HR-negative, [ER-/PgR-/AR-]). Subtyping was evaluated with respect to prognosis and to taxane therapy. High histologic grade (p < 0.001) and increased proliferation (p = 0.001) more often appeared in MAC and HR-negative than in luminal tumors. Patients with MAC had outcome comparable to the luminal group, while patients with HR-negative disease had increased risk for relapse and death. MAC outcome was favorable upon taxane-containing treatment; this remained significant upon multivariate analysis for overall survival (HR 0.31, 95%CI 0.13-0.74, interaction p = 0.035) and as a trend for time to relapse (p = 0.15). In conclusion, AR-related subtyping of breast cancer may be prognostic and serve for selecting optimal treatment combinations., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Angiogenesis is active in localised laryngeal squamous cell carcinoma. We assessed relative messenger RNA (mRNA) and immunohistochemical (IHC) expression of Vascular Endothelial Growth Factors (VEGF) A, B, C, their receptors VEGFR1, 2, 3, Neuropilins 1, 2 (NRP1, 2) and Hypoxia-Inducible Factor 1A (HIF1A) in paraffin-embedded localised laryngeal carcinomas. In 289 patients with T3-4 (77.8%), node-negative (84.1%) tumours of the larynx, high VEGFA and VEGFR1 mRNA correlated with advanced T stage, while low VEGFB and VEGFC mRNA with alcohol abuse and supraglottic primary, respectively (p<0.05). Age <55 was associated with high IHC expression of VEGFA, C and poor tumour differentiation with high IHC VEGFA. At a median follow-up of 74.5months, patients with VEGFR1-high tumours had significantly poorer disease-free survival (Hazard Ratio [HR] 1.93, p=0.008) and shorter overall survival (OS, HR 1.71, p=0.041). An association with dismal OS was seen for high VEGFR3 tumoural mRNA expression (HR 1.76, p=0.02). IHC expression of VEGF family proteins in the tumour was not prognostic and had poor concordance with mRNA expression (kappa<0.1, p=NS). In multivariate analysis, node-positive status, non-supraglottic localization, high VEGFR1 mRNA and high IHC VEGFA expression were significantly associated with relapse, while node-positive status, high VEGFR1 and VEGFC mRNA expression in the tumour with risk of death. In laryngeal cancer, upregulated mRNA expression of VEGFR1 and VEGFC is associated with poor patient outcome., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Unlabelled: The CXCL13-CXCR5 is a chemokine axis that is activated in some breast cancers. A total of 321 tissue blocks from a group of patients who received adjuvant, dose-dense chemotherapy for high-risk early breast cancer were examined. Activation of this axis was found to be associated with determinants of poor prognosis but also with improved outcome in the human epidermal growth factor receptor 2 overexpressing subpopulation., Background: Chemokines are important in cell migration and are thought to play a key role in metastasis. We explored the prognostic significance of C-X-C ligand-motif (CXCL) 12, CXCL13, and receptor (CXCR) 5 on disease-free survival (DFS) and overall survival (OS) in early breast cancer., Methods: A total of 595 patients with high risk, [corrected] early breast cancer were treated in a 2-arm trial (HE10/97) with dose-dense sequential epirubicin followed by cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) with or without paclitaxel. RNA was extracted from 321 formalin-fixed paraffin-embedded primary tumor tissue samples and quantitative reverse-transcriptase polymerase chain reaction was used to assess messenger RNA (mRNA) expression of CXCL12, CXCL13, and CXCR5; estrogen receptor; progesterone receptor (PgR); microtubule-associated protein tau and human epidermal growth factor receptor 2 (HER2)., Results: CXCL13 and CXCR5 were found to be negatively associated with estrogen receptor and microtubule-associated protein tau mRNA expression and with dense lymphocytic infiltration, and were positively associated with nuclear grade. Only CXCL13 was positively associated with HER2. Multivariate analysis revealed an association between high CXCL13 mRNA expression and improved DFS (hazard ratio [HR] 0.48 [95% CI, 0.25-0.90]; Wald, P = .023) but not OS; whereas high CXCL12 expression was significantly associated with increased OS (HR 0.53 [95% CI, 0.33-0.85]; Wald, P = .009). In the HER2 mRNA overexpressing subgroup, high CXCL13 mRNA expression was associated with improved DFS (P < .001), whereas high CXCR5 was associated with increased DFS and OS (P = .004 and P = .049, respectively)., Conclusions: The CXCL13-CXCR5 axis is associated with classic determinants of poor prognosis, such as high grade, hormone receptor negativity, and axillary node involvement. Interestingly, this chemokine axis seems to be strongly associated with improved outcome in patients with HER2(+) disease., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Concomitant administration of radiation therapy (RT) and chemotherapy with cisplatin (CCRT) is considered standard treatment in patients with locally advanced nasopharyngeal cancer (LA-NPC). The role of induction chemotherapy (IC) when followed by CCRT in improving locoregional control remains controversial., Patients and Methods: Totally, 141 eligible patients with LA-NPC were randomized to either three cycles of IC with cisplatin 75 mg/m(2), epirubicin 75 mg/m(2) and paclitaxel (Taxol) 175 mg/m(2) (CEP) every 3 weeks followed by definitive RT (70 Gy) and concomitant weekly infusion of cisplatin 40 mg/m(2) (investigational arm, 72 patients) or to the same CCRT regimen alone (control arm, 69 patients)., Results: Sixty-two patients (86%) received three cycles of IC. No difference between the arms was observed in the number of patients who completed RT (61 versus 64, P = 018). Overall and complete response rates were very similar in the two arms and so were 3-year progression-free and overall survival rates. Grade III or IV toxic effects from IC were infrequent, apart of alopecia. Mucositis, weight loss and leukopenia were the most prominent side-effects from CCRT., Conclusion: IC with three cycles of CEP when followed by CCRT did not significantly improve response rates and/or survival compared with that of CCRT alone.

Background: Paclitaxel (Taxol) and vinorelbine have shown synergism of cytotoxic effects in vitro and clinical activity in phase I and II studies. This combination was compared prospectively with the paclitaxel/gemcitabine regimen in non-operable non-small-cell lung cancer., Patients and Methods: Chemotherapy-naive patients, stage IIIbwet and IV with performance status (0-1), were randomized to receive paclitaxel 200 mg/m(2) on day 1 plus gemcitabine 1 gm/m(2) (group A) on days 1 and 8 every 3 weeks or paclitaxel 80 mg/m(2) plus vinorelbine 22.5 mg/m(2) (group B) on days 1, 8 and 15 every 4 weeks., Results: A total of 398 out of 415 patients were eligible for analysis on intent-to-treat basis (group A: 196, group B: 202). Progression-free survival (PFS) was 5.0 months [95% confidence interval (CI) 4.3-5.6] and 4.4 months (95% CI 3.7-5.2) for groups A and B respectively (P=0.365). Median survival was 11.1 months (95% CI 9.2-13.0) and 8.6 months (95% CI 7.0-10.2) for groups A and B respectively (P = 0.147). Grade 3/4 neutropenia and leukopenia were worse in group B (P<0.001, in both cases). Febrile neutropenia and severe infections were more prominent (P<0.001, P=0.029 respectively) in group B., Conclusion: Although response rate, PFS and survival were non-different in both groups, toxicity was significantly worse in group B and therefore further investigation of P-Vin is of no value., (© The Author 2010. Published by Oxford University Press on behalf of the European Society for Medical Oncology.)