Circulating tumor DNA profile recognizes transformation to castration-resistant neuroendocrine prostate cancer.

Loss of androgen receptor (AR) signaling dependence occurs in approximately 15%-20% of advanced treatment-resistant prostate cancers, and this may manifest clinically as transformation from a prostate adenocarcinoma histology to a castration-resistant neuroendocrine prostate cancer (CRPC-NE). The diagnosis of CRPC-NE currently relies on a metastatic tumor biopsy, which is invasive for patients and sometimes challenging to diagnose due to morphologic heterogeneity. By studying whole-exome sequencing and whole-genome bisulfite sequencing of cell free DNA (cfDNA) and of matched metastatic tumor biopsies from patients with metastatic prostate adenocarcinoma and CRPC-NE, we identified CRPC-NE features detectable in the circulation.

What Is the Real Impact of Estrogen Receptor Status on the Prognosis and Treatment of HER2-Positive Early Breast Cancer?

HER2 early breast cancer is a heterogeneous disease, comprising all the intrinsic breast cancer subtypes. The only biomarker available nowadays for anti-HER2 treatment selection is HER2 status itself, but estrogen receptor (ER) status is emerging as a robust predictive marker within HER2 disease. In this Perspective, we discuss the biological and clinical differences between patients with HER2/ER-positive (ER) disease versus those with HER2/ER-negative (ER-neg) tumors, namely, short-term and long-term (>5 years after diagnosis) prognosis, response to neoadjuvant treatment and benefit from adjuvant anti-HER2-targeted therapies.

Correction: Quality of life under extended continuous versus intermittent adjuvant letrozole in lymph node-positive, early breast cancer patients: the SOLE randomised phase 3 trial.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Effectiveness of Adalimumab for the Treatment of Psoriatic Arthritis: An Italian Real-Life Retrospective Study.

Few studies have evaluated the effectiveness of adalimumab in the real-life setting in psoriatic arthritis (PsA). To evaluate the 2-year retention rate of adalimumab in PsA patients. Potential baseline parameters influencing persistence on treatment were also evaluated.

The impact of the interleukin 12/23 inhibitor ustekinumab on the risk of infections in patients with psoriatic arthritis.

: Psoriatic arthritis (PsA) is characterized by chronic inflammation mediated by pro-inflammatory cytokines, with clinical features resulting from dysfunctional integrated signaling pathways affecting different constituents of the immune system. Increased understanding of the processes responsible for enthesitis, synovial inflammation, joint erosion, and new bone formation during PsA has led to development of biologic therapies targeting these cytokines. There is an increased risk of opportunistic infections in patients with PsA, and this risk is increased further with targeted biologic therapy.

No Confirmed Cases of Taeniasis in a Group of Recently Arrived Sub-Saharan Migrants to Italy.

One-hundred and sixty-four migrants from Sub-Saharan Africa to Italy were screened with the specific enzyme-linked immunosorbent assay coproantigen (ELISA CoAg) and four (2.4%) were recorded as positive, but with optical density values near to the cut-off. No ELISA CoAg positive samples were confirmed by parasitological methods.

Estimating the magnitude of clinical benefit from (neo)adjuvant chemotherapy in patients with ER-positive/HER2-negative breast cancer.

Gene-expression assays were originally validated retrospectively as tools of prognostication, with evidence emerging from more recent prospectively-conducted studies such as MINDACT and TAILORx supporting their clinical validity and utility as biomarkers in identifying patients with luminal breast cancer who might be spared chemotherapy. However, these assays still do not have the ability to identify all patients who may safely avoid chemotherapy, and may over-estimate the risk of relapse in some cases. Future studies should aim to prospectively integrate contemporary approaches that assume a theoretical risk of relapse (based on pathological and/or genomic evaluation of the primary tumour), with new tools that can detect signals of active micro-metastatic disease.

The Emerging Role of Mutations in Luminal Breast Cancer as a Prognostic and Predictive Biomarker of Response to Endocrine Therapy.

Mutations in the hotspot ligand-binding domain of the estrogen receptor (ER) gene have recently been recognized as mechanisms of endocrine resistance in endocrine receptor-positive metastatic breast cancer (MBC). Accumulating data suggest these mutations develop under the selective pressure of endocrine treatments, and are infrequent in untreated ER-positive breast cancers. In vitro studies show that these mutations confer ligand-independent activity, resistance to estrogen deprivation, and relative resistance to tamoxifen and fulvestrant.

Incidence of T790M in Patients With NSCLC Progressed to Gefitinib, Erlotinib, and Afatinib: A Study on Circulating Cell-free DNA.

Background: Insights into the mechanism of resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) could provide important information for further patient management, including the choice of second-line treatment. The EGFR T790M mutation is the most common mechanism of resistance to first- and second-generation EGFR TKIs. Owing to its biologic relevance in the response of non-small-cell lung cancer (NSCLC) to the selective pressure of treatment, the present study investigated whether the occurrence of T790M at progression differed among patients receiving gefitinib, erlotinib, or afatinib.

Biosimilars for the treatment of psoriatic arthritis.

: In recent years, biosimilars of reference adalimumab (re-ADA), etanercept (re-ETN) and infliximab (re-IFX) have been licensed. In the absence of specific controlled studies, by the extrapolation principle, biosimilars have been approved for the treatment of psoriatic arthritis (PsA).: To assess the efficacy and safety of biosimilars in PsA, the literature, present until 30 June 2019, was reviewed.

Absolute Improvements in Freedom From Distant Recurrence to Tailor Adjuvant Endocrine Therapies for Premenopausal Women: Results From TEXT and SOFT.

Purpose: The Tamoxifen and Exemestane Trial (TEXT)/Suppression of Ovarian Function Trial (SOFT) showed superior outcomes for premenopausal women with hormone receptor (HR)-positive breast cancer treated with adjuvant exemestane plus ovarian function suppression (OFS) or tamoxifen plus OFS versus tamoxifen alone. We previously reported the magnitude of absolute improvements in freedom from any recurrence across a continuous, composite measure of recurrence risk to tailor decision making. With longer follow-up, we now focus on distant recurrence.

Inclusion of Platinum Agents in Neoadjuvant Chemotherapy Regimens for Triple-Negative Breast Cancer Patients: Development of GRADE (Grades of Recommendation, Assessment, Development and Evaluation) Recommendation by the Italian Association of Medical Oncology (AIOM).

In the absence of identified therapeutic targets, chemotherapy is the main systemic treatment option for triple-negative breast cancer (TNBC). The achievement of a pathological complete response (pCR) after neoadjuvant chemotherapy leads to good outcome, whereas patients not achieving a pCR are at high risk of relapse. Various trials have evaluated the inclusion of platinum in neoadjuvant chemotherapy regimens for TNBC, leading to non-univocal results.

Cyclin-Dependent Kinase 4/6 Inhibitors in Neoadjuvant Endocrine Therapy of Hormone Receptor-Positive Breast Cancer.

The landscape of therapeutic options for the treatment of hormone receptor (HR)-positive (HR) HER2 breast cancer (BC) has been profoundly changed by the introduction of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors into the metastatic setting. Currently all CDK4/6 inhibitors are approved only in the metastatic setting by Food and Drug Administration (FDA) and European Medicine Agency (EMA), whereas their role in the neoadjuvant setting is still at an investigational stage. Exploitation of novel agents such as CDK4/6 inhibitors to improve the efficacy of neoadjuvant endocrine therapy (ET) or to overcome de novo resistance to ET is an area of research under active evaluation.

Distinct HR expression patterns significantly affect the clinical behavior of metastatic HER2+ breast cancer and degree of benefit from novel anti-HER2 agents in the real world setting.

We analyzed data from 738 HER2-positive metastatic breast cancer (mbc) patients treated with pertuzumab-based regimens and/or T-DM1 at 45 Italian centers. Outcomes were explored in relation to tumor subtype assessed by immunohistochemistry (IHC). The median progression-free survival at first-line (mPFS1) was 12 months.

Core Biopsies from Prostate Cancer Patients in Active Surveillance Protocols Harbor PTEN and MYC Alterations.

Background: Genomic characterization of prostate cancer (PCa) biopsies may improve criteria for the selection of patients suitable for active surveillance (AS).

Objective: To identify somatic genomic aberrations associated with adverse outcome as AS protocol exclusion indicators.

Design, Setting And Participants: Whole-exome sequencing profiles were generated for Gleason score (GS)=3+3 biopsies obtained from 54 PCa patients enrolled in two AS protocols.

Clinical outcomes after palbociclib with or without endocrine therapy in postmenopausal women with hormone receptor positive and HER2-negative metastatic breast cancer enrolled in the TREnd trial.

Currently, there is limited data regarding the effectiveness of standard subsequent line therapies such as endocrine therapy, chemotherapy, or targeted agents after progression on CDK4/6 inhibitor-based regimens. This paper describes time-to-treatment failure beyond progression on palbociclib or palbociclib+endocrine therapy in patients enrolled in the phase II, multicenter TREnd trial. Our results indicate that there is limited benefit from post-palbociclib treatment, regardless of the type of therapy received.

Pharmacotherapy for liposarcoma: current state of the art and emerging systemic treatments.

: Liposarcomas are a heterogeneous group of soft tissue tumors that arise from adipose tissue and are one of the most common soft tissue sarcomas found in adults. Liposarcomas are subclassified into four subtypes with distinct histologic and biologic features that influence their treatment and management. : This manuscript reviews the key clinicopathologic and cytogenic characteristics of the liposarcoma histologic subtypes and summarizes the results of recent clinical trials, treatment options, and future directions in the pharmacotherapy for the management of liposarcoma.

Sequencing of a 'mouse azoospermia' gene panel in azoospermic men: identification of RNF212 and STAG3 mutations as novel genetic causes of meiotic arrest.

Study Question: What is the diagnostic potential of next generation sequencing (NGS) based on a 'mouse azoospermia' gene panel in human non-obstructive azoospermia (NOA)?

Summary Answer: The diagnostic performance of sequencing a gene panel based on genes associated with mouse azoospermia was relatively successful in idiopathic NOA patients and allowed the discovery of two novel genes involved in NOA due to meiotic arrest.

What Is Known Already: NOA is a largely heterogeneous clinical entity, which includes different histological pictures. In a large proportion of NOA, the aetiology remains unknown (idiopathic NOA) and yet, unknown genetic factors are likely to play be involved.