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PurposeEndoPredict (EPclin) is a prognostic test validated to inform decisions on adjuvant chemotherapy to endocrine therapy alone for patients with oestrogen receptor-positive, HER2-negative breast cancer. Here, we determine the performance of EPclin for estimating 10-year distant recurrence-free interval (DRFI) rates for those who received adjuvant endocrine therapy (ET) alone compared to those with chemotherapy plus endocrine therapy (ET+C).MethodsA total of 3746 women were included in this joint analysis. 2630 patients received 5years of ET alone (ABCSG-6/8, TransATAC) and 1116 patients received ET+C (GEICAM 2003-02/9906). The primary objective was to evaluate the ability of EPclin to provide an estimate of the 10-year DR rate as a continuous function of EPclin separately for ET alone and ET+C. Cox proportional hazard models were used for these analyses.ResultsEPclin was highly prognostic for DR in women who received ET alone (HR 2.79 (2.49-3.13), P

Purpose: To assess the prognostic and predictive value of selected biomarkers involved in cell-cycle regulation or proliferation in patients with HER2-positive early breast cancer. Experimental Design: Protein expression of TOP2A, Ki67, cyclin D1, and p27 was immunohistochemically determined in tissue microarrays of surgical specimens from 862 patients randomized to trastuzumab (1 or 2 years; N ¼ 561) and observation (N ¼ 301) arms of the HERA trial. The primary analysis endpoint was disease-free survival (DFS). Biomarkers were examined as continuous or categorical variables (predefined cutoffs). Interaction terms between biomarkers and treatment were assessed in multivariate Cox models adjusted for variables of clinical interest. Results: A significant interaction was detected between p27 and treatment (adjusted P ¼ 0.0049). Trastuzumab effect was significant in the p27-low subgroup (70% p27-positive tumor cells; N ¼ 318). HRComb Trast vs.Obs 0.44, 95% CI, 0.29–0.65 (P < 0.001). No trastuzumab effect was observed in the p27-high subgroup N ¼ 435; HRComb Trast vs.Obs 0.97, 95% CI, 0.66–1.44, P ¼ 0.89), indicating that these patients derived little or no benefit from trastuzumab treatment. A prognostic effect of p27 on DFS was observed, with p27-high patients experiencing half the hazard of a DFS event compared with low ones (HRp27 High vs.Low 0.49, 95% CI, 0.32–0.75). TOP2A, Ki67, and cyclin D1, as categorical variables were not predictive, whereas cyclin D1 as continuous variable was predictive of trastuzumab benefit. Conclusions: In TransHERA, patients with HER2-positive early breast cancer with low p27 expression in their tumors benefited from trastuzumab treatment, whereas patients with high p27 expression did not. © 2018 American Association for Cancer Research.

Aris Giannos,1 Martin Filipits,2 Flora Zagouri,2,3 Anita Brandstetter,2 Alexandra Tsigginou,1 Maria Sotiropoulou,4 Irene Papaspyrou,4 Theodoros N Sergentanis,5 Theodora Psaltopoulou,5 Alexandros Rodolakis,1 Aris Antsaklis,1 Meletios-Athanasios Dimopoulos,2 Constantine Dimitrakakis1 1Department of Obstetrics and Gynaecology, Alexandra General Hospital, Medical School, University of Athens, Athens, Greece; 2Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; 3Department of Clinical Therapeutics, Alexandra General Hospital, Medical School, University of Athens, Athens, Greece; 4Department ofPathology, Alexandra General Hospital, Athens, Greece; 5Department of Hygiene, Epidemiology and Medical Statistics, Medical School, University of Athens, Athens, Greece Background/aim: In light of the controversial published literature, this study aims to examine the potential prognostic role of AR immunohistochemical expression in triple negative breast cancer (TNBC).Patients and methods: Ninety patients with TNBC were included in this study; the associations between AR expression (Allred score), clinicopathological variables (stage, grade, histological subtype, tumor size, nodal status, age at diagnosis, Ki67 expression, and p53 expression), and overall survival were evaluated.Results: AR expression was not associated with stage, grade, histological subtype, tumor size, nodal status, age at diagnosis, Ki67 expression, and p53 expression. AR immunopositivity was not associated with overall survival either at the univariate or at the multivariate Cox regression analysis (multivariate hazard ratio =0.66, 95% confidence interval: 0.26–1.70, P=0.393).Conclusion: AR expression does not seem to play a prognostic role in TNBC. Keywords: biomarkers, prognosis, AR, triple negative breast cancer

Background/aim: In light of the controversial published literature, this study aims to examine the potential prognostic role of AR immunohistochemical expression in triple negative breast cancer (TNBC). Patients and methods: Ninety patients with TNBC were included in this study; the associations between AR expression (Allred score), clinicopathological variables (stage, grade, histological subtype, tumor size, nodal status, age at diagnosis, Ki67 expression, and p53 expression), and overall survival were evaluated. Results: AR expression was not associated with stage, grade, histological subtype, tumor size, nodal status, age at diagnosis, Ki67 expression, and p53 expression. AR immunopositivity was not associated with overall survival either at the univariate or at the multivariate Cox regression analysis (multivariate hazard ratio =0.66, 95% confidence interval: 0.26–1.70, P=0.393). Conclusion: AR expression does not seem to play a prognostic role in TNBC. © 2015 Giannos et al.

Objectives We aimed to determine the prognostic significance of receptor activator of nuclear factor kappa-B ligand (RANKL), RANK and osteoprotegerin (OPG) in patients with oral squamous cell carcinoma (OSCC). Materials and methods The protein expression of RANKL, RANK and OPG was assessed by immunohistochemistry on pretreatment biopsies of 93 patients with locally advanced OSCC who received preoperative chemoradiotherapy (CRT). The primary endpoint was cancer-specific survival. Secondary endpoints were correlation of biomarkers with bone invasion and pathological tumor response. Kaplan-Meier curves and Cox regression models were used for survival analyses. Results A significantly higher OPG expression was demonstrated in patients with malignant bone invasion and non-responders to CRT as compared to patients without bone invasion and responders (p = 0.032 and p = 0.033, respectively). Multivariate analysis revealed that higher OPG expression was independently associated with shorter cancer-specific survival (p = 0.04). The expression status of RANKL and RANK was not significantly related to clinicopathological characteristics and had no impact on survival of OSCC patients. Conclusion Upregulation of OPG expression is associated with bone invasion, poor pathological tumor regression to neoadjuvant CRT, and worse long-term cancer-specific survival in patients with locally advanced OSCC. Our results indicate that OPG may be a novel prognostic biomarker in oral cancer. © 2014 Elsevier Ltd. All rights reserved.

Pertuzumab is a monoclonal antibody that represents the first among a new class of agents known as human epidermal growth factor receptor (HER) dimerization inhibitors. This is the first systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to synthesize all available data of pertuzumab in breast cancer. The search strategy retrieved 11 studies that evaluated pertuzumab. One study was conducted in the neoadjuvant setting (417 patients), whereas all the others dealt with patients with recurrent, metastatic, or refractory disease (1023 patients). Six studies were conducted in HER2+ breast cancer population (1354 patients), whereas 5 studies (86 patients) were conducted in HER2- (or unknown HER2 status) disease. Pertuzumab is the most recent agent approved by the US Food and Drug Administration in combination with trastuzumab and docetaxel for the treatment of patients with HER2+ metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease. This approval has been based on data from a phase III Clinical Evaluation of Pertuzumab and Trastuzumab (CLEOPATRA) study. The antitumor activity with the significant reduction in the risk of progression or death, as reflected upon the increase of 6.1 months in median progression-free survival, indicates that pertuzumab may provide an avenue for achieving additional benefit for patients with HER2+. Moreover, pertuzumab seems to have a putative role in the management of patients with HER2 who are resistant to trastuzumab. The promising role of pertuzumab in the neoadjuvant and adjuvant settings remains to be further investigated and established in the future. © 2013 Elsevier Inc. All rights reserved.

Pancreatic cancer is the fourth leading cause of cancer-related death. Most patients present with an advanced stage of disease that has a dismal outcome, with a median survival of approximately 6 months. Evidently, there is a clear need for the development of new agents with novel mechanisms of action in this disease. A number of biological agents modulating different signal transduction pathways are currently in clinical development, inhibiting angiogenesis and targeting epidermal growth factor receptor, cell cycle, matrix metalloproteinases, cyclooxygenase-2, mammalian target of rapamycin, or proteasome. This is the first systematic review of the literature to synthesize all available data coming from trials and evaluate the efficacy and safety of molecular targeted drugs in unresectable and metastatic pancreatic cancer. However, it should be stressed that although multiple agents have been tested, only 9 phase 3 trials have been conducted and one agent (erlotinib) has been approved by the Food and Drug Administration for use in clinical practice. As knowledge accumulates on the molecular mechanisms underlying carcinogenesis in the pancreas, the anticipated development and assessment of molecularly targeted agents may offer a promising perspective for a disease which, to date, remains incurable. Copyright © 2013 by Lippincott Williams & Wilkins.

Zielsetzung: Das maligne Pleuramesotheliom (MPM) ist eine aggressive, asbest-assoziierte Krebserkrankung mit begrenzten Therapieoptionen und schlechter Prognose. Fibroblasten Wachstumsfaktoren (FGF) und deren Rezeptoren (FGFR) regulieren Wachstum, Wanderungsverhalten und Überleben von Zellen und[for full text, please go to the a.m. URL], 21. Jahrestagung der Deutschen Gesellschaft für Thoraxchirurgie

Cervical cancer represents the third most common cause of female cancer mortality. Even with the best currently available treatment, a significant proportion of patients will experience recurrence and eventually die. Evidently, there is a clear need for the development of new agents with novel mechanisms of action in this disease. A number of biological agents modulating different signal transduction pathways are currently in clinical development, inhibiting angiogenesis, targeting epidermal growth factor receptor, cell cycle, histone deacetylases, cyclooxygenase-2 (COX-2), or mammalian target of rapamycin (mTOR). This is the first systematic review of the literature to synthesize all available data emerging from trials and evaluate the efficacy and safety of molecularly targeted drugs in cervical cancer. However, it should be stressed that relatively fewer molecularly targeted agents have been tested in cervical cancer in comparison with other cancer types; of note, no related phase 3 trials have been published and consequently no agent has been approved for use in clinical practice. Nevertheless, the promising results of bevacizumab in therapeutic trials for cervical cancer have shown that targeting the VEGF pathway is an attractive therapeutic strategy. As knowledge accumulates on the molecular mechanisms underlying carcinogenesis in the cervix, the anticipated development and assessment of molecularly targeted agents may offer a promising perspective for cervical cancer. © 2012 Elsevier Inc. All rights reserved.

Background: The purpose of this study was to evaluate whether the immunohistochemical expression of p53, p21, p27, cyclin D1, and Ki67 can predict therapy response and survival in patients with oral and oropharyngeal squamous cell carcinoma treated with preoperative chemoradiation. Methods: Biomarker expression was evaluated by immunohistochemistry in formalin-fixed, paraffin-embedded pretreatment biopsies of 111 homogenously treated patients. We assessed the association between clinicopathological variables including response to neoadjuvant chemoradiotherapy as well as the survival of the patients and the expression of the biomarkers as both dichotomized (positive vs. negative) and continuous variables. Results: Biomarker overexpression on the basis of pre-selected cutoff points was seen in 66 of 111 (59%) cases for p53, in 77 (69%) for p21, in 48 (43%) for p27, in 81 (73%) for cyclin D1, and in 54 (49%) cases for Ki67, respectively. None of the examined biomarkers was able to predict response to neoadjuvant chemoradiotherapy or was associated with survival outcome. Post-treatment pathologic TNM stage (P

Objective: Ovarian cancer in pregnancy is uncommon; however, this diagnosis adds complexity to cancer treatment recommendations. This is the first systematic review to synthesize all available data and evaluate the efficacy and safety of taxanes during pregnancy in ovarian cancer. Methods: This systematic review was performed in accordance with PRISMA guidelines. All studies that examined the efficacy and safety of taxanes administered during pregnancy in ovarian cancer, regardless of sample size, were considered eligible. Results: Overall, 8 articles (11 pregnancies, 12 newborns) were retrieved for paclitaxel and 1 for docetaxel (1 pregnancy, 1 newborn). In 92.31% of cases a healthy child was born, with a median follow-up of 20 months. The mean weight of the babies at delivery was 2,381 g. One study providing follow-up until the 11th year of age reported a case of attention deficit disorder. In 6 out of 8 case reports providing survival data, the mother was alive and disease free at the end of follow-up (ranging from 9.75 to 45 months). Conclusion: Taxanes may play a significant role in the treatment of ovarian cancer patients during the 2nd and 3rd trimesters. Before that, the risk of abortion or congenital anomalies is increased. Copyright © 2012 S. Karger AG, Basel.

PI3K/AKT/mTOR pathway is a crucial mediator of tumor progression. As the PI3K/Akt pathway is heavily deregulated in breast cancer, the application of mTOR inhibitors in breast cancer patients seems warranted. This is the first systematic review according to PRISMA guidelines to synthesize all available data of mTOR inhibitors in all subcategories of breast cancer. The search strategy retrieved 16 studies evaluating everolimus (1492 patients), seven studies examining temsirolimus (1245 patients), one study evaluating sirolimus (400 patients) and two studies evaluating MKC-1 (60 patients). The Breast Cancer Trials of Oral Everolimus-2 (BOLERO-2) study has marked a turning point in the evaluation of everolimus in the treatment of estrogen receptor positive breast cancer. Given the positive results, everolimus has entered NCCN 2012 guidelines, and its approval of its combination with exemestane by FDA and EMA is imminent. In addition, the promising antitumor activity and long-term disease control further suggest that mTOR inhibition with everolimus may provide an avenue for achieving long-lasting benefit from trastuzumab-based therapy in HER2-positive patients. Regarding temsirolimus, it seems that the agent may play, in the future, a role in the treatment of metastatic breast cancer; importantly, however, there is an unmet need to find its optimal target subpopulation. © 2012 Elsevier Inc. All rights reserved.

Hintergrund: Beim malignen Pleuramesotheliom (MPM) handelt es sich um eine asbest-assozierte neoplastische Erkrankung, die durch eine hohe Resistenz gegenüber den herkömmlichen zytostatischen Therapien und schlechter Prognose gekennzeichnet ist. Ziel dieser Studie war es, zu evaluieren, inwieweit[for full text, please go to the a.m. URL], Gemeinsame Jahrestagung der Deutschen, Österreichischen und Schweizer Gesellschaft für Thoraxchirurgie

The 110-kD lung resistance protein (LRP) is overexpressed in P-glycoprotein–negative multidrug-resistant cell lines and most likely involved in the multidrug resistance (MDR) of these cell lines. To determine the clinical significance of LRP, we have studied LRP expression of leukemic blasts and its association with clinical outcome in patients with de novo acute myeloid leukemia (AML). LRP expression of leukemic blasts obtained from peripheral blood or bone marrow of previously untreated patients (n = 86) was determined by immunocytochemistry by means of monoclonal antibody LRP-56. LRP expression at diagnosis was detected in 31 (36%) patients. LRP expression was independent of age and sex of the patients, French-American-British subtype, cytogenetic abnormalities, and lactate dehydrogenase levels, but correlated with white blood cell count (P = .01). Eighty-two patients received standard induction chemotherapy that included cytarabine and MDR drugs (daunorubicin in most patients, additional etoposide in the majority of patients). The complete remission rate of induction chemotherapy was 72% (95% confidence interval [CI] = 61% to 82%) for the total study population. The complete remission rate was 81% (95% CI = 67% to 91%) for patients without LRP expression but only 55% (95% CI = 36% to 74%) for patients with LRP expression (P = .01). Overall survival and disease-free survival were estimated according to Kaplan-Meier in 82 and 59 patients, respectively. Overall survival was significantly longer in patients without LRP expression than in patients with LRP expression. At a median follow-up of 16 months, median overall survival was 17 months (95% CI = 12 to 38 months) for LRP-negative patients but only 8 months (95% CI = 4 to 12 months) for -positive patients (P = .006). Disease-free survival was 9 months (95% CI = 7 to 11 months) for LRP-negative patients and 6 months (95% CI = 5 to 8 months) for -positive patients (P = .078). Outcome was best in patients lacking both LRP and P-glycoprotein expression. In conclusion, LRP predicts for poor outcome and thus theLRP gene appears to be another clinically relevant drug resistance gene in AML.