An historical approach to the genetic distribution of KIR and HLA ligands in Eastern Sicilians compared to modern descendants of their invaders.

A geographical stratification of Killer Immunoglobulin-like Receptors (KIR) has been reported worldwide. We first analyzed the distribution of 15 KIR genes in a sample of 50 East-Sicilians (ES). We used a Principal Component Analysis (PCA) to compare the KIR genetic content among ES and 10 modern populations who are descendants of the ancient invaders of Sicily: Spanish, French, Norwegians, Swedes, Finns, Tunisians, Moroccans, Arabs, Greeks, Turks.

Androgen receptor in estrogen receptor positive breast cancer: Beyond expression.

In recent years, new therapeutic approaches have reshaped the overall strategy of breast cancer (BC) treatment and have markedly improved patient survival. This is, in part, due to novel therapies for estrogen receptor (ER)-positive BC. Unfortunately, many patients present de novo resistance to these therapies or develop an acquired resistance over time.

Determinants of Last-line Treatment in Metastatic Breast Cancer.

Background: In metastatic breast cancer (MBC) patients, the identification of factors helping clinicians in the choice between active therapy versus best supportive care is needed clinically. The aim of the present study was to identify the clinicopathologic factors that could improve the prognostic valuation of MBC patients and clinical decision-making at the end of life.

Patients And Methods: The present study analyzed data from a retrospective series of 522 MBC patients treated at the oncology department (University Hospital of Udine) from January 2004 to June 2014.

Effect of Lipoic Acid on the Biochemical Mechanisms of Resistance to Bortezomib in SH-SY5Y Neuroblastoma Cells.

Neuroblastoma (NB) is an extracranial solid cancer and the most common cancer in infancy. Despite the standard treatment for NB is based on the combination of chemotherapeutic drugs such as doxorubicin, vincristine, cyclophosphamide, and cisplatin, chemoresistance occurs over the time. The aim of the present research was to evaluate the effect of bortezomib (BTZ) (50 nM) on NB cell viability and how lipoic acid (ALA) (100 μM) modifies pharmacological response to this chemotherapeutic agent.

Patterns of Care and Clinical Outcomes of HER2-positive Metastatic Breast Cancer Patients With Newly Diagnosed Stage IV or Recurrent Disease Undergoing First-line Trastuzumab-based Therapy: A Multicenter Retrospective Cohort Study.

Background: The aim of the study was to compare the patterns of care and clinical outcomes of HER2-positive metastatic breast cancer (MBC) patients with de novo or recurrent disease who underwent first-line trastuzumab-based therapy.

Patients And Methods: This was a multicenter retrospective cohort study including consecutive patients with HER2-positive MBC who received first-line trastuzumab-based therapy. Analyses on treatment response and effectiveness were conducted according to type of metastatic presentation (ie, de novo vs.

Efficacy and safety of eribulin in taxane-refractory patients in the 'real world'.

Aim: Recent clinical, randomized and observational studies showed that eribulin, an analogous of Halichondrin B, was beneficial and well-tolerated in heavily pretreated metastatic breast cancer patients. Here, we aim to evaluate the effectiveness and safety of eribulin in taxane-refractory metastatic breast cancer patients.

Patients & Methods: In this subanalysis of the ESEMPIO study database, we selected 91 subjects with well-defined taxane refractoriness and complete data available.

Tumor-infiltrating lymphocytes and molecular response after neoadjuvant therapy for HR+/HER2- breast cancer: results from two prospective trials.

Purpose: The aim was to evaluate the role of tumor-infiltrating lymphocytes (TIL) in predicting molecular response after preoperative endocrine or cytotoxic treatment for HR+/HER2- patients who do not achieve a pathological complete response.

Methods: Stromal (Str) TIL were centrally evaluated on samples from diagnostic core-biopsies of HR+/HER2- patients included in two prospective randomized trials: the LETLOB trial (neoadjuvant endocrine-based treatment) and the GIOB trial (neoadjuvant chemotherapy-based treatment). Pre- and post-treatment Ki67 was centrally assessed.

Pertuzumab and breast cancer: another piece in the anti-HER2 puzzle.

The mechanism of action of pertuzumab, a recombinant anti-HER2 humanized monoclonal antibody, is complementary to trastuzumab's. On 8 June 2012, the Food and Drug Administration approved the combination of pertuzumab with trastuzumab and docetaxel as first-line treatment of HER2-positive metastatic breast cancer. Furthermore, pertuzumab is the first drug to be approved in the neoadjuvant setting using a pathological complete response as an endpoint.

Dose-dense adjuvant chemotherapy in premenopausal breast cancer patients: A pooled analysis of the MIG1 and GIM2 phase III studies.

Background: No evidence exists to recommend a specific chemotherapy regimen in young breast cancer patients. We performed a pooled analysis of two randomised clinical trials to evaluate the efficacy of adjuvant dose-dense chemotherapy in premenopausal breast cancer patients and its impact on the risk of treatment-induced amenorrhoea.

Patients And Methods: In the MIG1 study, node-positive or high-risk node-negative patients were randomised to 6 cycles of fluorouracil/epirubicin/cyclophosphamide every 2 (dose-dense) or 3 (standard-interval) weeks.

BNC2 is a putative tumor suppressor gene in high-grade serous ovarian carcinoma and impacts cell survival after oxidative stress.

Rs3814113 is the single-nucleotide polymorphism (SNP) showing the strongest association with high-grade serous ovarian carcinoma (HGSOC) incidence and is located in an intergenic region about 44 kb downstream of basonuclin 2 (BNC2) gene. Lifetime number of ovulations is associated with increased risk to develop HGSOC, probably because of cell damage of extrauterine Müllerian epithelium by ovulation-induced oxidative stress. However, the impact of low-penetrance HGSOC risk alleles (e.

Chemotherapy versus endocrine therapy as first-line treatment in patients with luminal-like HER2-negative metastatic breast cancer: A propensity score analysis.

Background: According to current guidelines, endocrine therapy (ET) is recommended as first-line treatment of luminal-like metastatic breast cancer (MBC), whereas chemotherapy (CT) should be considered in presence of life-threatening disease. In daily practice, CT is often used outside of this clinical circumstance. Factors influencing first-line choice and the relative impact on outcome are unknown.

The prognostic performance of Adjuvant! Online and Nottingham Prognostic Index in young breast cancer patients.

Background: Limited data are available on the prognostic performance of Adjuvant! Online (AOL) and Nottingham Prognostic Index (NPI) in young breast cancer patients.

Methods: This multicentre hospital-based retrospective cohort study included young (⩽40 years) and older (55-60 years) breast cancer patients treated from January 2000 to December 2004 at four large Belgian and Italian institutions. Predicted 10-year overall survival (OS) and disease-free survival (DFS) using AOL and 10-year OS using NPI were calculated for every patient.

Final results of the TANIA randomised phase III trial of bevacizumab after progression on first-line bevacizumab therapy for HER2-negative locally recurrent/metastatic breast cancer.

Background: The randomised phase III TANIA trial demonstrated that continuing bevacizumab with second-line chemotherapy for locally recurrent/metastatic breast cancer (LR/mBC) after progression on first-line bevacizumab-containing therapy significantly improved progression-free survival (PFS) compared with chemotherapy alone [hazard ratio (HR) = 0.75, 95% confidence interval (CI) 0.61-0.

Antiproliferative and Antiangiogenic Effects of Punica granatum Juice (PGJ) in Multiple Myeloma (MM).

Multiple myeloma (MM) is a clonal B-cell malignancy characterized by an accumulation of clonal plasma cells (PC) in the bone marrow (BM) leading to bone destruction and BM failure. Despite recent advances in pharmacological therapy, MM remains a largely incurable pathology. Therefore, novel effective and less toxic agents are urgently necessary.

Real-time tests of multiple genome alterations take the first steps into the clinic: a learning example.

Molecular characterization is increasingly changing clinical practice, in both diagnosis and treatment. BRAF is a proto-oncogene that is mutated in ~2%-4% of lung cancers, but the incidence rises to 40%-45% among papillary thyroid cancers. Furthermore, BRAF is a promising target in lung cancer treatment.

Caring for cancer survivors: perspectives of oncologists, general practitioners and patients in Italy.

Aim: The present survey investigates the views of medical oncologists, general practitioners (GPs) and patients about the various surveillance strategies.

Methods: An online survey was conducted in Italy on a population of 329 medical oncologists, 380 GPs and 350 patients.

Results: Most of GPs (n = 291; 76%) claim that follow-up should be provided by the collaboration between GPs and medical oncologists.

Conformational modulation mediated by polyglutamine expansion in CAG repeat expansion disease-associated proteins.

We have previously reported TR-FRET based immunoassays to detect a conformational change imparted on huntingtin protein by the polyglutamine expansion, which we confirmed using biophysical methodologies. Using these immunoassays, we now report that polyglutamine expansion influences the conformational properties of other polyglutamine disease proteins, exemplified by the androgen receptor (associated with spinal bulbar muscular atrophy) and TATA binding protein (associated with spinocerebellar ataxia 17). Using artificial constructs bearing short or long polyglutamine expansions or a multimerized, unrelated epitope (mimicking the increase in anti-polyglutamine antibody epitopes present in polyglutamine repeats of increasing length) we confirmed that the conformational TR-FRET based immunoassay detects an intrinsic conformational property of polyglutamine repeats.

A Delphi consensus and open debate on the role of first-line bevacizumab for HER2-negative metastatic breast cancer.

To gain consensus on the role of bevacizumab plus paclitaxel as first-line treatment for HER2-negative metastatic breast cancer, a panel of expert oncologists experienced in treating patients with metastatic breast cancer in Italy participated in a Delphi consensus study. The panel reached a full consensus on the efficacy of bevacizumab plus paclitaxel and the clinical meaningfulness of the progression-free survival benefit compared with paclitaxel alone, despite the lack of an overall survival effect in clinical trials. The participants agreed that real-world data support the effectiveness and well-defined safety profile of the regimen.

Do platinum salts fit all triple negative breast cancers?

Triple-negative breast cancer (TNBC) is an aggressive disease with limited treatment options and poor prognosis once metastatic. Pre-clinical and clinical data suggest that TNBC could be more sensitive to platinum-based chemotherapy, especially among BRCA1/2-mutated patients. In recent years, several randomised trials have been conducted to evaluate platinum efficacy in both early-stage and advanced TNBC, with conflicting results especially for long-term outcomes.

Low-Dose Oral Cyclophosphamide and Methotrexate Maintenance for Hormone Receptor-Negative Early Breast Cancer: International Breast Cancer Study Group Trial 22-00.

Purpose: To evaluate the benefit of low-dose cyclophosphamide and methotrexate (CM) maintenance, which previously demonstrated antitumor activity and few adverse effects in advanced breast cancer, in early breast cancer.

Patients And Methods: International Breast Cancer Study Group (IBCSG) Trial 22-00, a randomized phase III clinical trial, enrolled 1,086 women (1,081 intent-to-treat) from November 2000 to December 2012. Women with estrogen receptor- and progesterone receptor-negative (< 10% positive cells by immunohistochemistry) early breast cancer any nodal and human epidermal growth factor receptor 2 status, were randomly assigned anytime between primary surgery and 56 days after the first day of last course of adjuvant chemotherapy to CM maintenance (cyclophosphamide 50 mg/day orally continuously and methotrexate 2.

Central nervous system involvement in breast cancer patients: Is the therapeutic landscape changing too slowly?

Central nervous system (CNS) involvement from breast cancer (BC) has been historically considered a relatively rare event. However, the development of new therapeutic strategies with a better control of extra-cranial disease and a longer overall survival (OS) has determined an increased incidence of brain metastases. Patients with HER2-positive or triple negative BC have higher occurrence of CNS involvement than patients with luminal-like disease.

Adjuvant ovarian function suppression and cognitive function in women with breast cancer.

Background: To examine the effect on cognitive function of adjuvant ovarian function suppression (OFS) for breast cancer.

Methods: The Suppression of Ovarian Function (SOFT) trial randomised premenopausal women with hormone receptor-positive breast cancer to 5 years adjuvant endocrine therapy with tamoxifen+OFS, exemestane+OFS or tamoxifen alone. The Co-SOFT substudy assessed objective cognitive function and patient reported outcomes at randomisation (T0), and 1 year later (T1); the primary endpoint was change in global cognitive function, measured by the composite objective cognitive function score.