Direct comparison study of DNA methylation markers in EpCAM-positive circulating tumour cells, corresponding circulating tumour DNA, and paired primary tumours in breast cancer.

Circulating Tumour Cells (CTCs) and circulating tumour DNA (ctDNA) represent a non-invasive liquid biopsy approach for the follow-up and therapy management of cancer patients. We evaluated whether DNA methylation status in CTCs and ctDNA is comparable and whether it reflects the status of primary tumours. We compared the methylation status of three genes, SOX17, CST6 and BRMS1 in primary tumours, corresponding CTCs and ctDNA in 153 breast cancer patients and healthy individuals, by using real time methylation specific PCR.

Predictive value of ATP7b, BRCA1, BRCA2, PARP1, UIMC1 (RAP80), HOXA9, DAXX, TXN (TRX1), THBS1 (TSP1) and PRR13 (TXR1) genes in patients with epithelial ovarian cancer who received platinum-taxane first-line therapy.

To evaluate the predictive value of genes involved in resistance to platinum-taxane chemotherapy in patients with epithelial ovarian cancer (EOC). Microdissected formalin-fixed tumoral samples from 187 EOC patients' primary tumors (90 and 97 samples from matched patients in the experimental and validation sets, respectively) were analyzed. All specimens were analyzed for ATP7b, BRCA1, BRCA2, PARP1, UIMC1(RAP80), HOXA9, DAXX, TXN (TRX1), THBS1 (TSP1) and PRR13 (TXR1) mRNA expression by quantitative real-time PCR.

Dose-dense FEC followed by docetaxel versus docetaxel plus cyclophosphamide as adjuvant chemotherapy in women with HER2-negative, axillary lymph node-positive early breast cancer: a multicenter randomized study by the Hellenic Oncology Research Group (HORG).

Background: Sequential administration of anthracycline and taxane is the current standard of care adjuvant regimen for node-positive early breast cancer. Due to long-term toxicity concerns, anthracycline-free regimens have been developed. We compared a sequential dose-dense anthracycline and taxane regimen with the anthracycline-free regimen of docetaxel and cyclophosphamide.

Direct Comparison of Metastasis-Related miRNAs Expression Levels in Circulating Tumor Cells, Corresponding Plasma, and Primary Tumors of Breast Cancer Patients.

Background: Circulating tumor cells (CTCs) and microRNAs (miRNAs) are important in liquid biopsies in which peripheral blood is used to characterize the evolution of solid tumors. We evaluated the expression levels of miR-21, miR-146a, miR-200c, and miR-210 in CTCs of breast cancer patients with verified metastasis and compared their expression levels in corresponding plasma and primary tumors.

Methods: Expression levels of the miRNAs were quantified by quantitative reverse transcription PCR (RT-qPCR) in (a) 89 primary breast tumors and 30 noncancerous breast tissues and (b) CTCs and corresponding plasma of 55 patients with metastatic breast cancer and 20 healthy donors.

Six versus 12 months of adjuvant trastuzumab in combination with dose-dense chemotherapy for women with HER2-positive breast cancer: a multicenter randomized study by the Hellenic Oncology Research Group (HORG).

Background: Adjuvant trastuzumab in combination with chemotherapy improves survival of women with HER2-positive early breast cancer. In this study, we compared 12 versus 6 months of adjuvant trastuzumab.

Patients And Methods: Axillary node-positive or high-risk node-negative women with HER2-positive early breast cancer were randomized to receive 12 or 6 months of adjuvant trastuzumab concurrently with dose-dense, granulocyte colony-stimulating factor (G-CSF)-supported docetaxel (75 mg/m(2) every 14 days for four cycles).

Whole Grain Consumption and Breast Cancer: A Case-Control Study in Women.

Objective: Whole grain consumption has long been associated with human health. However, its relationship with breast cancer remains not well understood and appreciated. The aim of this work was to evaluate the association between whole grain consumption and breast cancer in women.

A rapid and accurate closed-tube Methylation-Sensitive High Resolution Melting Analysis assay for the semi-quantitative determination of SOX17 promoter methylation in clinical samples.

Introduction: SOX17 promoter methylation can provide important prognostic information in cancer. We developed a novel semi-quantitative MS-HRMA assay for SOX17 promoter methylation.

Methods: The assay was optimized by using synthetic control samples and validated by analyzing 165 clinical samples: a) 107 formalin fixed paraffin embedded (FFPEs) samples of patients with early breast cancer, b) 27 FFPE samples of patients with metastatic breast cancer, c) 15 reduction mammoplasty specimens obtained from healthy women and d) 16 genomic DNA samples isolated from healthy blood donors.

Meat consumption and breast cancer: a case-control study in women.

Background: The relationship between meat intake and breast cancer has been inconsistent .

Objective: The aim of this work was to evaluate the association between meat intake and breast cancer, in women.

Design: A case-control study with 250 consecutive, newly diagnosed breast-cancer-female-patients (56 ± 12 years) and 250, one-to-one age-matched controls was conducted.

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.

PIK3CA mutational status in circulating tumor cells can change during disease recurrence or progression in patients with breast cancer.

Purpose: Molecular characterization of circulating tumor cells (CTC) is crucial for the investigation of molecular-targeted therapies while PIK3CA somatic mutations play a crucial role in therapy response. We investigated the presence of PIK3CA mutations in CTC and whether this is associated with clinical outcome.

Experimental Design: We developed and validated an ultrasensitive methodology for the detection of PIK3CA mutations that is based on a combination of allele-specific, asymmetric rapid PCR and melting analysis.

Dietary patterns and breast cancer: a case-control study in women.

Purpose: Since dietary habits have been associated with breast cancer, the tested research hypothesis was the associations between food patterns, as derived through multivariate methods, and breast cancer.

Methods: In a case-control study, Two-hundred and fifty consecutive, newly diagnosed breast cancer female patients (56 ± 12 years) and 250 one-to-one age-matched, healthy controls were studied. A standardized, validated questionnaire assessing various socio-demographic, clinical, lifestyle, and dietary characteristics was applied through face-to-face interviews.

The role of Ki-67 in the proliferation and prognosis of breast cancer molecular classification subtypes.

The Ki-67 antigen was identified in the early steps of polymerase I-dependent ribosomal RNA synthesis. Although it seems that this protein has an important function in cell division, its exact role is still unclear and there is little published work on its overall function. The aim of the present study was to evaluate the contribution of the level of Ki-67 with respect to tumor recurrence in molecularly classified groups of breast cancer patients.

Adherence to the Mediterranean diet is associated with lower likelihood of breast cancer: a case-control study.

Mediterranean diet has long been associated with human health. However, its relationship with breast cancer remains not well understood and appreciated. The aim of this work was to evaluate the association between adherence to the Mediterranean diet and its inherent constituents, with breast-cancer.

A multicenter phase I-II study of docetaxel plus epirubicin plus bevacizumab as first-line treatment in women with HER2-negative metastatic breast cancer.

Purpose: To assess the efficacy and toxicity of docetaxel (D) plus epirubicin (E) in combination with bevacizumab (B) [DEB regimen] as front-line treatment in patients with metastatic breast cancer (MBC).

Patients And Methods: Women with previously untreated HER2-negative MBC received B (15 mg/kg), E (75 mg/m2) and D (75 mg/m2) with prophylactic G-CSF support every 3 weeks (q3w) for up to 9 cycles followed by B (15 mg/kg q3w) until disease progression. Primary endpoint was the overall response rate (ORR).

Maintenance chemotherapy or not in ovarian cancer stages IIIA, B, C, and IV after disease recurrence.

Purpose: Ovarian cancer may have a high percentage of residual disease after chemotherapy. It is questionable whether second or more lines of chemotherapy are needed in patients with slow-growing residual disease. In the present trial we compared the median survival of patients with residual or recurrent disease who received 1-2 lines of chemotherapy with those who received 3-9 lines.

SOX17 promoter methylation in circulating tumor cells and matched cell-free DNA isolated from plasma of patients with breast cancer.

Introduction: Detection of circulating tumor cells (CTCs) and cell-free DNA (cfDNA) in the peripheral blood of patients with solid tumors has been widely studied for the early detection of metastatic spread. We evaluated whether there was an association between the origin of cfDNA and CTCs. We investigated whether SRY (sex determining region Y)-box 17 (SOX17) promoter methylation in CTCs was associated with the methylation pattern of this gene in matched cfDNA isolated from plasma of patients with breast cancer.

Aims, design and methods of a case-control study for the assessment of the role of dietary habits, eating behaviors and environmental factors, on the development of breast cancer.

In this work the aims, methodology and procedures of a case-control study that was developed for assessing the role of dietary habits, eating behaviors and environmental factors on the development of breast cancer, is presented. During 2010-2012, 250 consecutive women patients, newly diagnosed with breast cancer and 250 population-based, healthy subjects (controls) age-matched to the cases, were enrolled. Socio-demographic, dietary, psychological, lifestyle as well as environmental characteristics (i.

Final results of an international retrospective observational study in patients with advanced breast cancer treated with oral vinorelbine-based chemotherapy.

Background: Full oral chemotherapy (CT) is an active and convenient therapeutic option for patients with advanced breast cancer (ABC). In this retrospective analysis, we reviewed the characteristics and the outcome of patients treated by oral vinorelbine either as a single-agent or in combination with capecitabine as first- or second-line CT in the metastatic setting.

Patients And Methods: We analysed 216 patients with ABC who started treatment with a full oral CT at 13 centers and seven countries between 2006 and 2008.

CST6 promoter methylation in circulating cell-free DNA of breast cancer patients.

Objectives: We have recently shown that detection of CST6 promoter methylation in primary breast tumors can provide important prognostic information in patients with operable breast cancer and that CST6 promoter is also methylated in Circulating Tumor Cells (CTC). In this study we evaluated the presence of CST6 promoter methylation in cell-free DNA (cfDNA) circulating in plasma of breast cancer patients.

Design And Methods: Our study material consisted of: a) a pilot testing group of 27 patients with stage I-III operable breast cancer, 46 patients with verified metastasis and 37 healthy donors and b) an independent cohort of 123 consecutive stage I-III operable breast cancer patients.

A multicenter randomized phase III trial of vinorelbine/gemcitabine doublet versus capecitabine monotherapy in anthracycline- and taxane-pretreated women with metastatic breast cancer.

Background: The Breast Cancer Study Group of the Hellenic Oncology Research Group conducted a phase III trial of single-agent capecitabine versus the vinorelbine/gemcitabine doublet in patients with metastatic breast cancer (MBC) pretreated with anthracyclines and taxanes. The primary objective was to demonstrate superiority of combination treatment in terms of progression-free survival (PFS).

Patients And Methods: Women with MBC were randomly assigned to receive either capecitabine (Cap arm: 1250 mg/m(2) twice daily, on days 1-14) or vinorelbine/gemcitabine doublet (VG arm: vinorelbine 25 mg/m(2); gemcitabine 1000 mg/m(2); both drugs on days 1 and 15).

DNA methylation of tumor suppressor and metastasis suppressor genes in circulating tumor cells.

Background: Circulating tumor cells (CTCs) are associated with prognosis in a variety of human cancers and have been proposed as a liquid biopsy for follow-up examinations. We show that tumor suppressor and metastasis suppressor genes are epigenetically silenced in CTCs isolated from peripheral blood of breast cancer patients.

Methods: We obtained peripheral blood from 56 patients with operable breast cancer, 27 patients with verified metastasis, and 23 healthy individuals.

A phase I trial of oral metronomic vinorelbine plus capecitabine in patients with metastatic breast cancer.

Purpose: To determine the dose-limiting toxicities (DLTs) and the maximum tolerated doses (MTD) of oral metronomic vinorelbine with capecitabine in patients with metastatic breast cancer (MBC).

Patients And Methods: Escalated doses of oral metronomic vinorelbine (starting dose 30 mg) every other day continuously and capecitabine (starting dose 800 mg/m(2) bid) on days 1-14 every 21 days were administered. DLTs were evaluated during the first cycle.

Molecular characterization of circulating tumor cells in breast cancer by a liquid bead array hybridization assay.

Background: Molecular characterization of circulating tumor cells (CTCs) is crucial to identify novel diagnostic and therapeutic targets for individualized therapies. We developed a multiplexed PCR-coupled liquid bead array to detect the expression of multiple genes in CTCs.

Methods: mRNA isolated from immunomagnetically enriched CTCs was subjected to multiplex PCR for KRT19 (keratin 19; also known as CK19), ERBB2 [v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian); also known as HER2], SCGB2A2 (secretoglobin, family 2A, member 2; also known as MGB1, mammaglobin A), MAGEA3 (melanoma antigen family A, 3), TWIST-1 [twist homolog 1 (Drosophila)], and HMBS (hydroxymethylbilane synthase; also known as PBGD).

Depression, anxiety and general psychopathology in breast cancer patients: a cross-sectional control study.

Objective: A significant proportion of breast cancer patients experience psychiatric morbidity. The present study compared the psychopathological profile (depression, anxiety and general psychopathology) of Greek women with breast cancer with a group of healthy controls.

Materials And Methods: Patients (n=109) were recruited from a specialized oncology breast cancer department and healthy controls (n=71) from a breast outpatient clinic.