Targeted agents for HER2-positive breast cancer in older adults: current and future perspectives

ABSTRACT

Introduction: One-third of breast cancer (BC) cases worldwide occur in women aged 65 years and older, with 10 to 15% overexpressing the human epidermal growth factor receptor 2 (HER2). Although several HER2-targeted therapies have been developed, the lack of data regarding their use in older patients hampers evidence-based decision-making for this population.

Areas Covered: We review current evidence on the efficacy and safety of HER2-targeted therapies in older adults with BC, focusing on approved therapies such as trastuzumab, lapatinib, pertuzumab, ado-trastuzumab-emtansine, and neratinib. Additionally, we discuss drugs under development to target the HER2-receptor, and to overcome resistance to existing therapies. Finally, we highlight the cardiotoxicity of HER2-targeted drugs among older adults.

Expert Opinion: Older adults are underrepresented in trials of HER2-targeted therapies in BC. We propose strategies to increase recruitment of older adults in clinical trials in order to increase the evidence base to treat this growing population.     

Melanotic Neuroectodermal Tumor of Infancy: the Use of Immunohistochemical Analysis

The Melanotic Neuroectodermal Tumor of Infancy (MNTI) is an asymptomatic, pigmented neoplasm characterized by a fast and locally aggressive growth along with a rare tissue formation. In the diagnostic process, the use of imaging exams can suggest a local destruction suggestive of malignancy, a sign of bone remodeling and expansion. Therefore, as any early diagnosis minimizes risks and improves the prognosis of treatment for the patient, the aim of this study was, based on a clinical case report, to corroborate the use of histopathological analysis associated with immunohistochemistry. Thus, we conclude that the immunohistochemical exam is of great importance for a better complementation of the MNTI diagnosis process. In addition, it can reveal signs of possible aggressive growth.     

Valorization of Grape Pomace and Berries as a New and Sustainable Dietary Supplement: Development,Characterization, and Antioxidant Activity Testing

Grape pomace and berries represent natural sources of phytochemicals that can increase the quality of life of consumers by contributing to the prevention of chronic diseases; thus, the development of a dietary supplement was necessary. The raw material (r.m.) used for the development of the dietary supplement consisted of dried and powdered bilberries (Vaccinium myrtillus L.), red currants (Ribes rubrum L.), and red fermented pomaces (Vitis vinifera L.) from Feteasca Neagra and Cabernet Sauvignon cultivars. The particle size distribution, powder flow, total phenolic content (TPC), HPLC-DAD phenolic profile assessment, and radical scavenging assay (RSA) were employed for the analysis of the raw material. After encapsulation, the average mass and uniformity of mass, the disintegration, and the uniformity of content for the obtained capsules were performed to obtain a high-quality dietary supplement. All the assays performed complied to the compendial requirements and the TPC was determined at 9.07 ± 0.25 mg gallic acid equivalents/g r.m. and RSA at 48.32 ± 0.74%. The highest quantities of phenolic compounds determined were 333.7 ± 0.50 µg/g r.m. for chlorogenic acid, followed by rutin, ferulic acid, and (+)-catechin with 198.9 ± 1.60 µg/g r.m., 179.8 ± 0.90 µg/g r.m. and 118.7 ± 0.75 µg/g r.m., respectively. The results of this study can be used for the manufacturing and assessing of pilot scale-up capsule batches and thinking of quality assurance, we recommend that the industrial batch extracts should be standardized in polyphenols, and the manufacturing process should be validated.     

Safety and Efficacy of Eucaloric Very Low-Carb Diet (EVLCD) in Type 1 Diabetes: A One-Year Real-Life Retrospective Experience

A eucaloric very low carbohydrate diet (EVLCD) is a diet with a daily caloric intake equal to the total daily energy expenditure (TDEE) with a carbohydrate content of <50 g/day. The literature on very low carbohydrate diets (VLCD) in type 1 diabetes (DM 1) is limited, although recently published scientific studies have highlighted their safety and efficacy in managing DM 1. In this retrospective analysis, we report the clinical data of 33 patients affected by DM 1 carrying out insulin therapy who switched voluntarily from their usual diet (high carb, low fat) to an EVLCD. Our aim is to evaluate the glycemic control, the amount of insulin needed in order to maintain glycemic control and safety of EVLCD. The switch improved glycemic control (mean glycated hemoglobin decreased from 8.3% to 6.8% (p < 0.01). The number of patients who reached a glycated hemoglobin value of <7% increased statistically from 12% to 57% (p < 0.01), and there was a statistically significant decrease (p < 0.01) in the units of daily insulin (from 36.7± 14.9 IU to 28.9 ±9.1 IU) A reduction from 54% to 24% in clinical level 2 hypoglycemia episodes was reported. No cases of severe hypoglycemia or ketoacidosis were observed. The results of the study support that EVLCD in DM 1 seems safe and effective when adopted under tight medical supervision.     

Substandard application of preimplantation genetic screening may interfere with its clinical success

The intent of this study was to evaluate a recent randomized clinical trial evaluating the effect of preimplantation genetic screening (PGS) that reports a negative effect on pregnancy outcome. This article reviews appropriate PGS techniques and how they differ from the trial in question. A closer look at the clinical trial in question reveals significant lack of expertise in biopsy, cell fixation, genetic analysis, and patient selection. At most, this trial demonstrates that in inexperienced hands, PGS can be detrimental. No other conclusions concerning the effect of PGS on pregnancy results can be drawn from the trial.     

Fatigue Analysis and Defect Size Evaluation of Filled NBR including Temperature Influence

The fatigue behavior of a filled non-crystallizing elastomer was investigated on axisymmetric dumbbell specimens. By plotting relevant Wöhler curves, a power law behavior was found. In addition, temperature increases due to heat build-up were monitored. In order to distinguish between initiation and crack growth regimes, hysteresis curves, secant and dynamic moduli, dissipated and stored energies, and normalized minimum and maximum forces were analyzed. Even though indications related to material damaging were observed, a clear trend to recognize the initiation was not evident. Further details were revealed by considering a fracture mechanics. The analysis of the fracture surfaces evidenced the presence of three regions, associated to initiation, fatigue striation, and catastrophic failure. Additional fatigue tests were performed with samples in which a radial notch was introduced. This resulted in a reduction in lifetime by four orders of magnitude; nevertheless, the fracture surfaces revealed similar failure mechanisms. A fracture mechanics approach, which considered the effect of temperature, was adopted to calculate the critical defect size for fatigue, which was found to be approximately 9 μm. This value was then compared with the particle size distribution obtained through X-ray microcomputed tomography (μ-CT) of undamaged samples and it was found that the majority of the initial defects were indeed smaller than the calculated one. Finally, the evaluation of J-integral for both unnotched and notched dumbbells enabled the assessment of a geometry-independent correlation with fatigue life.     

Prevalence of Delirium in End-of-Life Palliative Care Patients: An Observational Study

ObjectivesThe aim of this study was to assess the prevalence of delirium, using the Assessment Test for Delirium and Cognitive Impairment (4AT) in end-of-life palliative care patients.Subjects and MethodsThis retrospective cross-sectional study was conducted on end-of-life patients in a hospice or at home. All patients were evaluated with the 4AT for the presence of delirium.ResultsOf the 461 patients analyzed, 76 (16.5%) were inpatients and 83.5% (385) outpatients. The median age was 79.5 (72–86) years, and 51.0% were female. According to the 4AT score, 126 patients (27.3%) had delirium (A4T ≥4) at admission, 28 (36.8%) were inpatients, and 98 (25.5%) outpatients. Around 33.8% of the cancer inpatients had delirium, while 20.6% of the cancer outpatients had delirium. The prevalence of delirium varied according to the setting, clinical condition, and life expectancy. In addition, 55.0% (11) actively dying inpatients, within 3 days, had delirium, and 56.7% (17) outpatients had delirium; while among those with life expectancy longer than 4 days, 30.4% (17) inpatients and 22.8% (81) outpatients were with delirium.ConclusionsOur study confirms that delirium is common in cancer and noncancer palliative care patients. Further research on delirium in end-of-life palliative care patients should consider the complexity of palliative care of this population as well as of the characteristics of the settings.