Treating advanced breast cancer with metronomic chemotherapy: what is known, what is new and what is the future?

The prognosis for patients with locally advanced or metastatic breast cancer (mBC) remains poor, with a median survival of 2-4 years. About 10% of newly diagnosed breast cancer patients present with metastatic disease, and 30%-50% of those diagnosed at earlier stages will subsequently progress to mBC. In terms of ongoing management for advanced/metastatic breast cancer after failure of hormonal therapy, there is a high medical need for new treatment options that prolong the interval to the start of intensive cytotoxic therapy, which is often associated with potentially serious side effects and reduced quality of life.

A meta-analysis of clinical benefit rates for fulvestrant 500 mg vs. alternative endocrine therapies for hormone receptor-positive advanced breast cancer.

Background: Fulvestrant, a selective estrogen receptor degrader, is approved for first- and second-line treatment of postmenopausal women with hormone receptor-positive advanced breast cancer (ABC).

Methods: Meta-analysis of randomized controlled trials (RCTs) evaluating fulvestrant 500 mg in postmenopausal hormone receptor-positive ABC, to evaluate differences in clinical benefit rate (CBR; proportion of patients experiencing best overall response of complete response, partial response, or stable disease for ≥ 24 weeks) between fulvestrant 500 mg and comparator endocrine therapies. Odds ratios (OR) and 95% confidence intervals (CI) for CBR were calculated; fixed effects (FE) models were constructed (first- and second-line data, alone and combined).

Risk of tuberculosis reactivation associated with traditional disease modifying anti-rheumatic drugs and non-anti-tumor necrosis factor biologics in patients with rheumatic disorders and suggestion for clinical practice.

Introduction: Two classes of biologics, anti-tumor necrosis factor (TNF) and non-anti-TNF targeted, are currently available for the treatment of rheumatic diseases.

Areas Covered: Discussion on the need for LTBI diagnosis in rheumatic patients treated csDMARDs and non-anti-TNFs through a review of the literature. The literature, updated to 15 April 2019, on tuberculosis (TB) reactivation risk in patients exposed to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and non-anti-TNF biologics was reviewed.

Prognostic role of serum thymidine kinase 1 activity in patients with hormone receptor-positive metastatic breast cancer: Analysis of the randomised phase III Evaluation of Faslodex versus Exemestane Clinical Trial (EFECT).

Background: Thymidine kinase 1 (TK1) plays a critical role in DNA synthesis and cell proliferation. Recent studies have shown potential for serum TK1 activity (sTKa) as a prognostic marker and indicator of early response to endocrine therapy in advanced breast cancer. The aim of this study is to assess the correlation between sTKa and patient outcome.

Characterization of QuantiFERON-TB-Plus results in latent tuberculosis infected patients with or without immune-mediated inflammatory diseases.

Objectives: Screening for latent tuberculosis infection (LTBI) diagnosis is mandatory in patients with immune-mediated inflammatory diseases (IMID) requiring biologics. QuantiFERON-TB-Plus (QFT-P), an LTBI diagnostic test, measures IFN-γ after M. tuberculosis-stimulation in TB1 and TB2 tubes in which a "CD4" or a "CD4 and CD8" response is respectively elicited.

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

Background: In the phase III SOLE trial, the extended use of intermittent versus continuous letrozole for 5 years did not improve disease-free survival in postmenopausal women with hormone receptor-positive breast cancer. Intermittent therapy with 3-month breaks may be beneficial for patients' quality of life (QoL).

Methods: In the SOLE QoL sub-study, 956 patients completed the Breast Cancer Prevention Trial (BCPT) symptom and further QoL scales up to 24 months after randomisation.

Benefit from anti-EGFRs in and wild-type metastatic transverse colon cancer: a clinical and molecular proof of concept study.

Objective: Primary tumour location is regarded as a reliable surrogate of colorectal cancer biology. Sensitivity to anti-EGFRs (Epidermal Growth Factor Receptor) of metastatic transverse colon cancers (mTCCs) has usually been assumed similar to right-sided tumours; however, evidence about the clinical behaviour of mTCC is limited. Thus, to verify sensitivity of mTCC to anti-EGFRs we conducted the present study.

Standard treatment and emerging drugs for managing synovial sarcoma: adult's and pediatric oncologist perspective.

in this review we discuss the standard of care for both pediatric and adult synovial sarcoma (SS), the prognostic differences between them, and the treatments available for localized and advanced diseases. We also overview the biology and the recent drugs under consideration in clinical trials on SS. Areas covered: we focus on new targeted therapies being investigated for advanced SS, especially anti-angiogenic drugs, and immunotherapy.

Preoperative Denosumab With Curettage and Cryotherapy in Giant Cell Tumor of Bone: Is There an Increased Risk of Local Recurrence?

Background: Denosumab is a monoclonal RANKL antibody, which was originally introduced for the treatment of osteoporosis and bone metastases from solid tumors, but more recently has been used for treatment of giant cell tumor of bone (GCTB). In GCTB, denosumab has been used as a single agent in patients with inoperable tumors; it also has been used before surgery in some patients with the aim to downstage the tumor to facilitate a joint-preserving procedure (curettage) rather than a resection. However, few studies are available evaluating the benefits and risks of denosumab for the latter indication.

Therapeutic strategies utilization and resource consumption in patients treated for psoriatic arthritis: findings from a real-world analysis in an Italian setting.

Purpose: The purpose of this study was to analyze the therapeutic strategies and estimate the health care resource consumption in patients with psoriatic arthritis (PsA).

Patients And Methods: An observational retrospective cohort analysis of administrative databases of six Italian Local Health Units was performed. Patients ≥18 years with a hospitalization discharge diagnosis of PsA (International Classification of Diseases, Ninth Revision code: 696.

The optimal duration of adjuvant endocrine therapy in early luminal breast cancer: A concise review.

Patients with luminal early breast cancer are at risk of relapse, even after five years of adjuvant endocrine therapy. To date, no biomarkers have been clinically validated to identify those patients at risk of late recurrence, who might benefit from extended adjuvant endocrine therapy. In recent decades, multiple clinical trials have tested the role of extending adjuvant endocrine therapies in patients with luminal disease.

MONARCH 3 final PFS: a randomized study of abemaciclib as initial therapy for advanced breast cancer.

At the MONARCH 3 interim analysis, abemaciclib plus a nonsteroidal aromatase inhibitor (AI) significantly improved progression-free survival (PFS) and objective response rate (ORR) with a tolerable safety profile as initial treatment for hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC). MONARCH 3 is a randomized, phase III, double-blind study of abemaciclib/placebo (150 mg twice daily, continuous) plus nonsteroidal AI (1 mg anastrozole or 2.5 mg letrozole, daily).

Association of Smoking and Obesity on the Risk of Developing Primary Sjögren Syndrome: A Population-based Cohort Study.

Objective: To explore the role of smoking and obesity in primary Sjögren syndrome (pSS).

Methods: Olmsted County (Minnesota, USA) residents (n = 106) diagnosed with pSS from 2000 to 2015 were compared to 3 controls without pSS and matched for age and sex who were randomly selected from Olmsted County residents.

Results: Current smokers were less likely to be pSS cases (OR 0.

Neoadjuvant Degarelix Versus Triptorelin in Premenopausal Patients Who Receive Letrozole for Locally Advanced Endocrine-Responsive Breast Cancer: A Randomized Phase II Trial.

Purpose: To evaluate endocrine activity in terms of ovarian function suppression (OFS) of degarelix (a gonadotropin-releasing hormone [GnRH] antagonist) versus triptorelin (a GnRH agonist) in premenopausal patients receiving letrozole as neoadjuvant endocrine therapy for breast cancer.

Patients And Methods: Premenopausal women with stage cT2 to 4b, any N, M0; estrogen receptor and progesterone receptor greater than 50%; human epidermal growth factor receptor 2-negative breast cancer were randomly assigned to triptorelin 3.75 mg administered intramuscularly on day 1 of every cycle or degarelix 240 mg administered subcutaneously (SC) on day 1 of cycle 1 then 80 mg SC on day 1 of cycles 2 through 6, both with letrozole 2.

ddSeeker: a tool for processing Bio-Rad ddSEQ single cell RNA-seq data.

Background: New single-cell isolation technologies are facilitating studies on the transcriptomics of individual cells. Bio-Rad ddSEQ is a droplet-based microfluidic system that, when coupled with downstream Illumina library preparation and sequencing, enables the monitoring of thousands of genes per cell. Sequenced reads show unique features that do not permit the use of freely available tools to perform single cell demultiplexing.

Managing advanced HR-positive, HER2-negative breast cancer with CDK4/6 inhibitors in post-menopausal patients: is there a best sequence?

The current therapeutic landscape of luminal human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (mBC) is fundamentally evolving, particularly in the advent of molecularly targeted therapies, such as inhibitors of mammalian target of rapamycin and cyclin-dependent kinase 4/6 (CDK4/6). In the context of CDK4/6 inhibitors, landmark clinical trials for palbociclib (PALOMA-1, PALOMA-2, PALOMA-3), ribociclib (MONALEESA-2, MONALEESA-3, MONALEESA-7) and abemaciclib (MONARCH-1, MONARCH-2, MONARCH-3) have provided solid data regarding progression-free survival and overall response rate, justifying the introduction of this class of drugs into our therapeutic armoury. However, several clinical questions remain open.

Red flags for appropriate referral to the gastroenterologist and the rheumatologist of patients with inflammatory bowel disease and spondyloarthritis.

Collaboration between gastroenterologists and rheumatologists is recommended for the correct management of patients with associated spondyloarthritis (SpA) and inflammatory bowel disease (IBD). We aimed to establish the appropriateness of several red flags for a prompt specialist referral. A systematic review of the literature was performed using the GRADE method to describe the prevalence of co-existing IBD-SpA and the diagnostic accuracy of red flags proposed by a steering committee.

Cyclin E1 and Rb modulation as common events at time of resistance to palbociclib in hormone receptor-positive breast cancer.

CDK4/6 inhibitors represent a new treatment standard for hormone receptor-positive (HR+), HER2-negative advanced breast cancer (BC) patients. Although efficacious, resistance to these agents is universal. Here, we profiled a large panel of HR+ BC cell lines with conditioned resistance to the CDK4/6 inhibitor palbociclib, and analyzed cell cycle-related markers by gene expression profiles (GEP) and western blot (WB).

Personalization of biologic therapy in patients with rheumatoid arthritis: less frequently accounted choice-driving variables.

Objective: To propose appropriate statements that drive the choice of biologic therapies in patients with rheumatoid arthritis (RA), factoring in their impact on the following issues: anti-drug antibody (ADAb) formation, suspicion and management of infections, lupus-like syndrome (LLS), effects on bone mass and sexual sphere, and relationship between RA and periodontal disease (PD).

Methods: An overview of existing evidence was undertaken by an expert panel on behalf of the Italian board for the TAilored BIOlogic therapy (ITABIO). Data were extracted from controlled trials, national registries, national health care databases, post-marketing surveys, and, when required by the paucity of controlled studies, from open-label clinical series.

Adjuvant Letrozole and Tamoxifen Alone or Sequentially for Postmenopausal Women With Hormone Receptor-Positive Breast Cancer: Long-Term Follow-Up of the BIG 1-98 Trial.

Purpose: Luminal breast cancer has a long natural history, with recurrences continuing beyond 10 years after diagnosis. We analyzed long-term follow-up (LTFU) of efficacy outcomes and adverse events in the Breast International Group (BIG) 1-98 study reported after a median follow-up of 12.6 years.

An Italian Delphi study to evaluate consensus on adjuvant endocrine therapy in premenopausal patients with breast cancer: the ERA project.

Background: Several trials evaluated the role of ovarian function suppression for the adjuvant treatment of premenopausal patients with hormone receptor-positive early breast cancer. Based on the results of the SOFT and TEXT trials, international guidelines recommend the addition of ovarian function suppression to standard adjuvant endocrine therapy for patients at higher risk of relapse.

Methods: The ERA project (Evaluation of Risk factors in the Adjuvant treatment of breast cancer in premenopausal patients) was devised with the objective of obtaining a consensus on the identification of risk factors and the use of ovarian function suppression in the adjuvant treatment of these women.