PARP inhibitors in testicular germ cell tumors: what we know and what we are looking for.

Testicular germ cell tumors (TGCTs), the most common malignancies affecting young men, are characterized by high sensitivity to cisplatin-based chemotherapy, which leads to high cure rates even in metastatic disease. However, approximately 30% of patients with metastatic TGCTs relapse after first-line treatment and those who can be defined as platinum-refractory patients face a very dismal prognosis with only limited chemotherapy-based treatment options and an overall survival of few months. Hence, to understand the mechanisms underlying cisplatin resistance is crucial for developing new treatment strategies.

Immune-Based Therapy in Triple-Negative Breast Cancer: From Molecular Biology to Clinical Practice.

Triple-negative breast cancer (TNBC) has been considered for many years an orphan disease in terms of therapeutic options, with conventional chemotherapy (CT) still representing the mainstay of treatment in the majority of patients. Although breast cancer (BC) has been historically considered a "cold tumor", exciting progress in the genomic field leading to the characterization of the molecular portrait and the immune profile of TNBC has opened the door to novel therapeutic strategies, including Immune Checkpoint Inhibitors (ICIs), Poly ADP-Ribose Polymerase (PARP) inhibitors and Antibody Drug Conjugates (ADCs). In particular, compared to standard CT, the immune-based approach has been demonstrated to improve progression-free survival (PFS) and overall survival (OS) in metastatic PD-L1-positive TNBC and the pathological complete response rate in the early setting, regardless of PD-L1 expression.

A Dose-finding Study of Metronomic Oral Vinorelbine in Combination With Oral Cyclophosphamide and Bevacizumab in Patients With Advanced Breast Cancer.

Background: Metronomic chemotherapy can induce disease control in patients with metastatic breast cancer (MBC) and has better safety profiles than conventional chemotherapy. Evidence suggests that cytotoxics can be anti-angiogenic in pre-clinical models and may have synergistic effects when combined with anti-vascular endothelial growth factor therapies.

Patients And Methods: Patients pretreated with ≥ 1 prior line of therapy for MBC received oral cyclophosphamide 50 mg daily in combination with oral vinorelbine at escalating doses of 20 mg (V20), 30 mg (V30), and 40 mg (V40) 3 times per week, and intravenous bevacizumab 15 mg/kg every 3 weeks.

Impact of COVID-19 outbreak on cancer immunotherapy in Italy: a survey of young oncologists.

Background: The coronavirus disease 2019 (COVID-19) pandemic has overwhelmed the health systems worldwide. Data regarding the impact of COVID-19 on cancer patients (CPs) undergoing or candidate for immune checkpoint inhibitors (ICIs) are lacking. We depicted the practice and adaptations in the management of patients with solid tumors eligible or receiving ICIs during the COVID-19 pandemic, with a special focus on Campania region.

Palbociclib added to ongoing endocrine therapy for hormone receptor-positive HER2-negative metastatic breast cancer: A case report series.

Palbociclib is a potent cyclin-dependent kinase (CDK)4/6 inhibitor that disrupts cell cycle progression and has been recently approved in combination with an aromatase inhibitor or fulvestrant as first- and second-line treatment in hormone receptor (HR), human epidermal growth factor receptor (HER)2 metastatic breast cancer. There is evidence that palbociclib may reverse endocrine therapy resistance and that it may also be added to ongoing endocrine therapy beyond progression to obtain clinical benefit. The aim of the present study was to explore this possibility in 5 patients who received palbociclib + fulvestrant following disease progression while under treatment with fulvestrant alone.

Plasma Thymidine Kinase Activity as a Biomarker in Patients with Luminal Metastatic Breast Cancer Treated with Palbociclib within the TREnd Trial.

Purpose: Thymidine kinase 1 (TK1) is downstream to the CDK4/6 pathway, and TK activity (TKa) measured in blood is a dynamic marker of outcome in patients with advanced breast cancer (ABC). This study explores TK1 as a biomarker of palbociclib response, both and in patients with ABC.

Experimental Design: Modulation of TK1 levels and activity by palbociclib were studied in seven estrogen receptor-positive breast cancer cell lines: sensitive (PDS) and with palbociclib acquired resistance (PDR).

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.

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.

Strain-oriented strategy for guiding cardioprotection initiation of breast cancer patients experiencing cardiac dysfunction.

Aims: This study assessed the impact of the strain-guided therapeutic approach on cancer therapy-related cardiac dysfunction (CTRCD) and rate of cancer therapy (CT) interruption in breast cancer.

Methods And Results: We enrolled 116 consecutive female patients with HER2-positive breast cancer undergoing a standard protocol by EC (epirubicine + cyclophosphamide) followed by paclitaxel + trastuzumab (TRZ). Coronary artery, valvular and congenital heart disease, heart failure, primary cardiomyopathies, permanent or persistent atrial fibrillation, and inadequate echo-imaging were exclusion criteria.

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.

CDK 4/6 Inhibitors as Single Agent in Advanced Solid Tumors.

Cyclin-dependent kinases (CDK) 4/6 inhibitors, namely abemaciclib, palbociclib, and ribociclib, interfere with cell cycle progression, induce cell senescence and might promote cancer cell disruption by a cytotoxic T cells-mediated effect. Phase III randomized clinical trials have proven that CDK4/6 inhibitors (CDK4/6i) in combination with several endocrine agents improve treatment efficacy over endocrine agents alone for hormone receptor positive (HR+) HER2 negative (HER2-) metastatic breast cancer (MBC). Based on such results, these combinations have been approved for clinical use.

Fractional microablative CO2 laser in breast cancer survivors affected by iatrogenic vulvovaginal atrophy after failure of nonestrogenic local treatments: a retrospective study.

Objective: Vulvovaginal atrophy (VVA) is a condition frequently observed in menopause. Its symptoms can significantly affect the quality of life of patients. Since VVA is related to estrogen deficiency, chemotherapy and hormone therapy for breast cancer (BC) might cause VVA by inducing menopause.