the science behind vitamins and natural compounds for breast cancer prevention getting the most prevention out of it

Summary This review highlights the role of vitamins and natural compounds in breast cancer prevention, with a particular focus on Vitamin D. In the last decades, both encouraging and discouraging results about the association between antioxidant supplementation and cancer have been reported to public and scientific community. Their safe and favorable toxicity profile makes them suitable to be investigated in a preventive setting. However, a recent large meta-analysis showed that treatment with beta carotene, vitamin A, and vitamin E may increase mortality, whereas the potential roles of vitamin C and selenium on mortality need further study. Likewise, folate levels were not associated with reduced breast cancer risk in a recent meta-analysis. Several studies have shown that a high proportion of women at-risk for breast cancer or affected by the disease have deficient vitamin D levels, i.e., 250H-

clinical benefit and risk of death with endocrine therapy in ovarian cancer a comprehensive review and meta analysis

Abstract Background Steroid hormones promote epithelial ovarian cancer (EOC) growth and their receptor expression is associated with disease outcome. Hormone therapy is frequently used in pretreated EOC, but the magnitude of activity overall and by specific agents or tumor characteristics is unknown. Methods Clinical Benefit Rates (CBR) and deaths from clinical trials of endocrine agents were meta-analyzed. Summary estimates of CBR (SCBR) and Odd Ratio for death (SOR) were calculated according with type of drug, ER and PgR status, platinum resistance, line of therapy, tumor grade and tamoxifen dose. Results Fifty-three trials in 2490 patients were analyzed. Overall, SCBR was 41% (95%CI, 0.34–0.48) for any endocrine treatment, 43% (95%CI, 0.30–0.56) for tamoxifen, 39% (95%CI, 0.29–0.50) for aromatase inhibitors and 37% (95%CI, 0.26–0.48) for progestins. The SCBR for ER + and/or PgR + tumors was 46% (95%CI, 0.34–0.57) versus 37% (95%CI, 0.27–0.48) in tumors with unknown receptors and 55% in platinum sensitive (95%CI, 0.28–0.80) versus 40% (95%CI, 0.29–0.51) in platinum resistant tumors The SOR for death calculated from 6 out of 9 randomized clinical trials (RCTs) showed a reduced mortality with endocrine therapy (SOR = 0.69, 95%CI, 0.50–0.97), with a possible tendency for a greater effect in first line and low grade tumors. The overall quality of the RCTs was low. Conclusions The activity of endocrine therapy in advanced EOC is worth considering and seems to support large properly designed randomized trials in the first treatment of hormone sensitive EOC

Identification of a prognostic signature based on the expression of genes related to the insulin pathway in early breast cancer

INTRODUCTION: Insulin and the insulin-like growth factor (IGF) family play a key role in breast cancer (BC). OBJECTIVE: In this study, we evaluated on a genomic scale the potential prognostic value of insulin signaling in early BC. METHODS: Candidate genes were selected from the published literature and gene expression profiling experiments. Three publicly available BC datasets, containing gene expression data on 502 cases, were used to test the prognostic ability of the score. The gene signature was developed on GSE1456, containing microarray data from 159 patients, split into a training set (102 breast tumors) and a validation set (n = 57). GSE3494 and GSE2990 (350 patients) were used for external validation. Univariate Mann-Whitney test was used to identify genes differentially expressed between relapsed and nonrelapsed patients. Expression of genes significantly correlated with relapse was combined in a linear score. Patients were classified as low or high risk with respect to the median value. RESULTS: On the training set, 15 genes turned out to be differentially expressed: 8-year disease-free survival (DFS) was 51 and 91% in the high- and low-risk group (p < 0.001), respectively. In the validation set, DFS was 97 and 54% (p = 0.009), respectively. External validation: 8-year DFS was 72 and 61%, respectively, in GSE3494 (p = 0.03) and 74 and 55% in GSE2990 (p = 0.03). By multivariate analyses, the insulin signature was significantly associated with DFS, independently of age, hormone receptor status, nodal status, and grade. CONCLUSIONS: Our findings indicate that the insulin pathway is involved in BC prognosis at a genomic level and provide a window of selectivity for preventive and treatment strategies targeting the insulin/IGF pathway in BC patients

Approval rating and opinion of outpatients and general practitioners toward generic drugs: a questionnaire-based real-world study

Purpose: Generic drugs use in the Liguria region is higher than the Italian average, but lower than in other European countries. No data exist about real-life prescription and level of awareness of generic drugs. In this study, we analyzed demographic, social, economic and cultural factors that may affect the level of awareness of generic drugs and their effective use. Methods: We conducted a population survey using a structured questionnaire, administered to a sample of 8 outpatient clinics of general practitioners located in different districts of Genoa (Liguria, Italy). Multivariate logistic modeling was adopted to study the relationship between awareness/use of generic drugs and characteristics of subjects. Results: Out of 2,000 outpatients surveyed, 95% were aware of generic drugs: these were mostly females (OR =2.2, 95% CI: 1.4\u20133.6), .35 years old (OR .6.0 vs 18\u201335 years), with a high level of education (OR .4.4 vs \u201celementary sch\u201d), living in the west side of the city (OR =1.9 vs center); of these, only 59% declared that they effectively use generic drugs. Users were younger (OR =3.1, 18\u201335 years vs .65 years), with a high level of education (high school/university degree vs no title/elementary/secondary school OR =1.7), and were aware of the lower cost compared with branded drugs, and were mainly informed by pharmacists and physicians. Conclusions: Although subjects were substantially aware of the existence of generic drugs, ~40% still did not use them; doubts about their efficacy seem to be mainly driven by the idea that cheaper drugs lead to lower product quality, in term

ERANET JTC 2011: Submission and Activation of an International Academic Translational Project in Advanced Breast Cancer. Experience From the ET-FES Study

Academic; Radiopharmaceuticals; Regulatory in EuropeAcadèmic; Radiofàrmacs; Regulador a EuropaAcadémico; Radiofármacos; Regulador en EuropaBackground: Academic research is important to face unmet medical needs. The Oncological community encounters many hurdles in setting up multicenter investigator-driven trials mainly due to administrative complexity. The purpose of a network organization at a multinational level is to facilitate clinical trials through standardization, coordination, and education for drug development and regulatory approval. Methods: The application of an European grant foresees the creation of a consortium which aims at facilitating multi-center academic clinical trials. Results: The ERA-NET TRANSCAN Call 2011 on “Validation of biomarkers for personalized cancer medicine” was released on December 2011. This project included Italian, Spanish, French and German centers. The approval process included Consortium constitution, project submission, Clinical Trial Submission, and activation on a national level. The different timescales for submitting study documents in each Country and the misalignment of objections by each Competent Authority CA, generated several requests for changes to the study documents which meant amendments had to be made; as requested by the 2001/20/EC Directive, the alignment of core documents is mandatory. This procedure impacted significantly on study activation timelines. Time to first patient in was 14, 10, 28, and 31 months from the date of submission in Italy, France, Spain, and Germany, respectively. Accrual was stopped on 22nd January 2021 due to an 18F FES shortage as the primary reason but also for having exceeded the project deadlines with consequent exhaustion of the funds allocated for the project. Conclusions: Pharmaceutical companies might be reluctant to fund research projects aimed at treatment individualization if the approval for a wider indication has already been achieved. Academic trials therefore become fundamental for promoting trials which are not attractive to big pharma. It was very difficult and time consuming to activate an academic clinical trial, for this reason, a study may become “old” as new drugs entered into the market. National institutions should promote the development of clinical research infrastructures and network with competence in regulatory, ethical, and legal skills to speed up academic research.This research received grants from ERANET JTC 2011

True prevalence of long COVID in children: a narrative review

Contrary to what is true for adults, little is known about pediatric long COVID (LC). Studies enrolling children are relatively few and extremely heterogeneous. This does not allow to draw definitive conclusions on the frequency and pathogenesis of pediatric LC and limits the development of appropriate and effective measures to contain the clinical, social and economic impact of this condition on the pediatric population. Depending on the methods used to collect and analyze data, studies have found that the incidence rate of pediatric LC may vary from about 25% to less than 5%. However, despite true prevalence of pediatric LC cannot be exactly defined, studies comparing children with previous COVID-19 and uninfected controls have shown that most of the clinical manifestations detected in infected children, mainly mood symptoms, mental health disorders and heart abnormalities could be diagnosed with similar frequency and severity in uninfected subjects also. This seems to indicate that SARS-CoV-2 is the cause of pediatric LC only in a part of children and other factors play a relevant role in this regard. Pandemic itself with the persistent disruption of child lives may have caused persistent stress in all the pediatric population causing mood symptoms, mental health disorders or several organ and body system functional alterations, regardless SARS-CoV-2 infection. These suppositions suggest the need for long-term physical control of all the children after COVID-19 especially when they were already suffering from an underlying disease or have had a severe disease. Moreover, attention should be paid to the assessment of change in children’s emotional and behavioral functioning in order to assure adequate interventions for the best emotional and behavioral well being. However, whatever its origin, it seems highly likely that the prevalence of the pediatric LC is set to decline in the future. Preliminary observations seem to suggest that recently developed SARS-CoV-2 variants are associated with less severe COVID-19. This suggests that, as already seen in adults, a lower number of pediatric virus-associated LC cases should occur. Furthermore, the use of COVID-19 vaccines, reducing incidence and severity of SARS-CoV-2 infection, may reduce risk of LC development. Finally, elimination of restrictive measures should significantly reduce mood symptoms and mental health disorders

Prognostic significance of VEGF after twenty-year follow-up in a randomized trial of fenretinide in non-muscle-invasive bladder cancer

Non-muscle-invasive bladder cancer (NMIBC) may progress to muscle-invasive disease, but no effective preventive treatments are available. In addition, no reliable prognostic biomarkers have been identified. We assessed the long-term effect of the oral retinoid fenretinide and the prognostic value of circulating VEGF levels. We updated through the Tumor Registry the vital status of 99 patients with resected Ta/T1 bladder tumors who were recruited in a randomized trial of 2 years of fenretinide or no treatment in 1993-1994. Serum VEGF levels measured at baseline and 12 months were available in a subgroup of 62 patients. After a median of 20.5 years, 54 subjects died, 35 of any cancer and 14 of bladder cancer. Neither overall survival (OS), nor cancer survival (CS) or bladder cancer survival (BCS) was affected by fenretinide (log-rank P 65 0.2). DNA aneuploidy in bladder washing was associated with shorter OS (P =0.02), CS (P =0.05), and BCS (P = 0.09). Subjects with baseline VEGF levels in the top quintile ( 65350 pg/mL) had a significantly shorter OS (P =0.01), CS (P = 0.02), and BCS (P= 0.008). The trend across quintiles of VEGF was significant for BCS (P =0.007). Multivariate analyses showed that, in addition to smoking status, VEGF level in the top quintile was an independent prognostic factor for OS (HR =2.7; 95% CI, 1.1-6.5), CS (HR = 3.3; 95% CI, 1.1-9.4) and BCS (HR =8.9; 95% CI,1.3-61). Fenretinide did not affect the long-term outcome of patients with NMIBC. High serum VEGF level was a significant predictor of overall and cancer death and may help to identify high-risk subjects who may benefit from a preventive therapy. Cancer Prev Res; 9(6); 437-44

Association of CYP2D6 genotype and tamoxifen metabolites with breast cancer recurrence in a low-dose trial

Low-dose tamoxifen halves recurrence in non-invasive breast cancer without significant adverse events. Some adjuvant trials with tamoxifen 20 mg/day had shown an association between low endoxifen levels (9–16 nM) and recurrence, but no association with CYP2D6 was shown in the NSABP P1 and P2 prevention trials. We studied the association of CYP2D6 genotype and tamoxifen metabolites with tumor biomarkers and recurrence in a randomized phase III trial of low-dose tamoxifen. Median (IQR) endoxifen levels at year 1 were 8.4 (5.3–11.4) in patients who recurred vs 7.5 (5.1–10.2) in those who did not recur (p = 0.60). Tamoxifen and metabolites significantly decreased C-reactive protein (CRP, p < 0.05), and a CRP increase after 3 years was associated with higher risk of recurrence (HR = 4.37, 95% CI, 1.14–16.73, P = 0.03). In conclusion, endoxifen is below 9 nM in most subjects treated with 5 mg/day despite strong efficacy and there is no association with recurrence, suggesting that the reason for tamoxifen failure is not poor drug metabolism.publishedVersio