A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers.

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies.

Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women.

Background: Genetic testing for breast cancer susceptibility is widely used, but for many genes, evidence of an association with breast cancer is weak, underlying risk estimates are imprecise, and reliable subtype-specific risk estimates are lacking.

Methods: We used a panel of 34 putative susceptibility genes to perform sequencing on samples from 60,466 women with breast cancer and 53,461 controls. In separate analyses for protein-truncating variants and rare missense variants in these genes, we estimated odds ratios for breast cancer overall and tumor subtypes.

Messenger-RNA Expression of Five Gemcitabine Sensitivity-related Genes Predicting Outcome in Advanced-stage Non-small Cell Lung Cancer.

Background/aim: Tumoural transcriptional levels of RRM1, RRM2, CDA, dCK and hENT1 genes are potential biomarkers for gemcitabine's efficacy in non-small cell lung cancer (NSCLC).

Patients And Methods: We retrospectively analysed each gene's relative mRNA expression by quantitative, real-time polymerase chain reaction in microdissected, formalin-fixed, paraffin-embedded primary-tumour specimens from 219 chemonaïve patients with advanced-stage NSCLC, treated with gemcitabine-based regimens within clinical trials. The five genes' transcriptional patterns were integrated into an ordinal, five-level gemcitabine-susceptibility classifier (5L-GSC).

Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes.

Genome-wide association studies have identified breast cancer risk variants in over 150 genomic regions, but the mechanisms underlying risk remain largely unknown. These regions were explored by combining association analysis with in silico genomic feature annotations. We defined 205 independent risk-associated signals with the set of credible causal variants in each one.

Polygenic Risk Scores for Prediction of Breast Cancer and Breast Cancer Subtypes.

Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to empirically validate the PRSs in prospective studies. The development dataset comprised 94,075 case subjects and 75,017 control subjects of European ancestry from 69 studies, divided into training and validation sets.

Estrogen receptor-alpha isoforms are the main estrogen receptors expressed in non-small cell lung carcinoma.

The expression profile of estrogen receptors (ER) in Non-Small Cell Lung Carcinoma (NSCLC) remains contradictory. Here we investigated protein and transcriptome expression of ERα wild type and variants. Tissue Micro-Arrays of 200 cases of NSCLC (paired tumor/non-tumor) were assayed by immunohistochemistry using a panel of ERα antibodies targeting different epitopes (HC20, 6F11, 1D5, ERα36 and ERα17p).

Association analysis identifies 65 new breast cancer risk loci.

Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry.

Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer.

Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease. We conducted a GWAS using 21,468 ER-negative cases and 100,594 controls combined with 18,908 BRCA1 mutation carriers (9,414 with breast cancer), all of European origin. We identified independent associations at P < 5 × 10 with ten variants at nine new loci.

Application of data mining techniques and data analysis methods to measure cancer morbidity and mortality data in a regional cancer registry: The case of the island of Crete, Greece.

Background And Objective: Micro or macro-level mapping of cancer statistics is a challenging task that requires long-term planning, prospective studies and continuous monitoring of all cancer cases. The objective of the current study is to present how cancer registry data could be processed using data mining techniques in order to improve the statistical analysis outcomes.

Methods: Data were collected from the Cancer Registry of Crete in Greece (counties of Rethymno and Lasithi) for the period 1998-2004.

Dose-dense paclitaxel versus docetaxel following FEC as adjuvant chemotherapy in axillary node-positive early breast cancer: a multicenter randomized study of the Hellenic Oncology Research Group (HORG).

Adding a taxane to anthracycline-based adjuvant chemotherapy prolongs survival in node-positive early breast cancer. However, which is the preferable taxane in a dose-dense regimen remains unknown. We conducted a randomized study to compare the efficacy of dose-dense paclitaxel versus docetaxel following 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) as adjuvant chemotherapy in women with node-positive early breast cancer.

A Paternally Inherited BRCA1 Mutation Associated with an Unusual Aggressive Clinical Phenotype.

This report highlights the necessity of genetic testing, at least for BRCA1 mutations, of young females diagnosed with triple negative breast cancer, even in the absence of or limited family history. A 34-year-old female with a locally advanced, triple negative tumour, which perforated the skin, is described. At the time of diagnosis, the patient had already multiple lung metastases and although chemotherapy was started immediately, she died with rapid systemic disease progression.

A 52-year-old-male patient with metastatic non-small-cell lung cancer and recurrent venous thromboembolism in unusual sites despite anticoagulation.

The link between cancer and venous thromboembolism is well known, with an annual incidence rate of venous thromboembolism between 0.5% and 20% depending on the primary site and background risk factors. Current guidelines suggest treatment with low-molecular-weight heparin over oral vitamin K antagonists.

The Glasgow Prognostic Score (GPS) predicts toxicity and efficacy in platinum-based treated patients with metastatic lung cancer.

Purpose: Lung cancer is the most common cause of cancer death. A cumulative prognostic score based on C-reactive protein and albumin, termed the Glasgow Prognostic Score (GPS), indicates the presence of systemic inflammatory response. GPS has been proposed as a powerful prognostic tool for patients with various types of malignant tumors, including lung cancer.

Trastuzumab combined to neoadjuvant chemotherapy in patients with HER2-positive breast cancer: a systematic review and meta-analysis.

Purpose: To perform a meta-analysis in order to quantify the actual cumulative randomized evidence for the benefit and toxicity of trastuzumab combined with neoadjuvant chemotherapy in HER2-positive breast cancer.

Methods: Potentially eligible trials were located through PubMed and Cochrane Library searches and abstracts of major international conferences. The endpoints that we assessed were pathologic complete response (pCR) rate, breast-conserving surgery (BCS) rate and toxicity.

Immunohistochemical study of the angiogenetic network of VEGF, HIF1α, VEGFR-2 and endothelial nitric oxide synthase (eNOS) in human breast cancer.

Background: The role of Nitric Oxide (NO) in angiogenesis has not been fully clarified yet. A dual role for NO, either inductive or inhibitory, has been proposed on the basis of different effects that high or low concentrations of NO may exert on the angiogenic process. Additionally, it has been referred that NO may induce VEGF production, while VEGF may induce NO production via up-regulation of the endothelial nitric oxide synthase (eNOS), the two pathways being reverse.

Hypofractionated accelerated CT-guided interstitial ¹⁹²Ir-HDR-Brachytherapy as re-irradiation in inoperable recurrent cervical lymphadenopathy from head and neck cancer.

Background: Despite significant improvements in the treatment of head and neck cancer (HNC), lymph node recurrences remain a clinical challenge after primary radiotherapy. The value of interstitial (IRT) brachytherapy (BRT) for control of lymph node recurrence remains unclear. In order to clarify its role a retrospective review was undertaken on the value of computed tomography (CT)-guided IRT high-dose-rate (HDR)-BRT in isolated recurrent disease from HNC.

Comparison of the pharmacokinetics of 68Ga-DOTATOC and [18F]FDG in patients with metastatic neuroendocrine tumours scheduled for 90Y-DOTATOC therapy.

Purpose: The purpose of this study was to evaluate and compare, by means of dynamic PET, the pharmacokinetics of 68Ga-DOTATOC, a tracer which reflects the expression of somatostatin receptors (SSTRs), and of [18F]FDG, a marker of tumour viability, in patients with metastatic neuroendocrine tumours (NETs) in whom 90Y-DOTATOC therapy was planned.

Materials And Methods: Fifteen patients (63 lesions) with confirmed metastatic NETs were enrolled in this study. Dynamic [18F]FDG and 68Ga-DOTATOC PET scans were performed on two different days in the same week.

Quantitative assessment of SSTR2 expression in patients with non-small cell lung cancer using(68)Ga-DOTATOC PET and comparison with (18)F-FDG PET.

Purpose: Dynamic PET studies with(68)Ga-DOTATOC were performed in patients with non-small cell lung cancer (NSCLC) to assess the somatostatin receptor 2 (SSTR2) expression. Furthermore, dynamic(18)F-fluorodeoxyglucose (FDG) studies were performed in the same patients to compare the SSTR2 expression with the tumour viability.

Methods: The study population comprised nine patients, examined with both tracers on two different days within 1 week.

Evaluation of the pharmacokinetics of 68Ga-DOTATOC in patients with metastatic neuroendocrine tumours scheduled for 90Y-DOTATOC therapy.

Purpose: The purpose of the study was to evaluate the pharmacokinetics of (68)Ga-DOTATOC in order to ascertain which parameters have the greatest impact on the global DOTATOC standardised uptake value (SUV), defined as the mean SUV of the last frame of the dynamic study 55-60 min p.i.

Methods: Twenty-two patients with 74 metastatic lesions were examined with dynamic (68)Ga-DOTATOC PET studies.

Sequential combination of paclitaxel-carboplatin and paclitaxel-liposomal doxorubicin as a first-line treatment in patients with ovarian cancer. A multicenter phase II trial.

Cisplatin or carboplatin plus paclitaxel is considered the standard first-line treatment in ovarian cancer. Attempts to maximize tumor cytoreduction with first-line chemotherapy by incorporating new promising agents led to sequential drug administration with two or three doublets. In the present study, we aimed to evaluate the activity and the tolerance of two sequential doublets (paclitaxel/carboplatin and liposomal doxorubicin/carboplatin) administered as first-line treatment in patients with FIGO III/IV ovarian cancer.

Phase I trial of weekly docetaxel with a 4-weekly cisplatin administration in patients with advanced gastric carcinoma.

The docetaxel-cisplatin combination is active against several tumors including gastric cancer but it is followed by severe myelosuppression. Recent experience with weekly taxanes has demonstrated a mild myelotoxicity with high dose intensity. We investigated in a phase I study a weekly schedule of docetaxel on days 1, 8 and 15 and cisplatin on day 1 every 4 weeks in 19 patients with advanced gastric cancer with no prior chemotherapy.

Salmonella enterica pneumonia in a patient with lung cancer.

A case of life-threatening Salmonella enterica serotype Enteritidis pneumonia in a febrile patient with lung cancer is described. The organism was isolated from the sputum, the protected specimen brush material of bronchial secretions, and the stool. Despite the early administration of appropriate and adequate treatment, the patient died 7 days after the onset of the infection.