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-

Hormonal Therapy and Chemoprevention.

Hormone replacement therapy (HRT) can increase the quality as well as the length of life, but a prolonged use can also increase the risk of breast cancer. The combination of HRT and a selective estrogen receptor modulator (SERM) such as tamoxifen may retain the benefits while reducing the risks of either agent. A post hoc analysis of the Italian Tamoxifen Prevention Study showed a borderline significant reduction of breast cancer among women who were on HRT continuously and tamoxifen as compared with continuous HRT users who received placebo. Recent studies suggest that the standard dose of tamoxifen may be reduced to one-quarter (i.e., 10 mg every other day) without loss of its beneficial biological effects. Since the endometrial effect of tamoxifen seems to be both dose and time dependent, a dose reduction could substantially reduce the risk of endometrial cancer while retaining its preventive efficacy. On the other hand, the addition of HRT containing progestins could also minimize the risk of endometrial cancer associated with tamoxifen. Moreover, estrogen should reduce the incidence of vasomotor and urogenital symptoms, which are a major reason for tamoxifen withdrawal in prevention studies. Notably, in the National Surgical Adjuvant Breast Project (NSABP) P-1 trial, women ages 50 or younger had no increased incidence of adverse events, including endometrial cancer and venous thromboembolic events. One possible explanation for the lack of toxicity in premenopause is the presence of adequate circulating estrogen levels which prevent tamoxifen to act as an estrogen agonist at these target tissues. Moreover, data from the current Italian tamoxifen prevention trial indicate that the compliance was substantially higher for de novo and current HRT users as compared to women who never received HRT during the study. The combination of HRT and tamoxifen at low doses could thus reduce the risks and side effects while retaining the benefits of either agent

Cohort study of prevalence and phenomenology of tremor in dementia with Lewy bodies

To study prevalence, specific patterns and response to treatment of tremor in dementia with Lewy bodies (DLB), in comparison with other tremulous disorders prevalence, qualitative and quantitative features of tremor were studied in an incident cohort of 67 dopaminergic treatment naive DLB, 111 Parkinson’s Disease (PD) and 34 Essential Tremor (ET) patients. Tremulous DLB patients (tDLB) were compared with tremulous PD (tPD) and ET patients and followed for 2 years. Double blind placebo-controlled acute drug challenge with l-Dopa and alcohol was performed in all ET, 24 tDLB and 27 tPD. Effects of dopaminergic chronic treatment in all tDLB and tPD patients and primidone in 8 tDLB were also assessed. Tremor occurred in 44.76 % of DLB patients. The tDLB patients presented a complex pattern of mixed tremors, characterized by rest and postural/action tremor, including walking tremor and standing overflow in 50 % tDLB. Standing tremor with overflow was characteristic of tDLB (p \u3c 0.001). Head tremor was more frequent in tDLB than tPD and ET (p = 0.001). The tDLB tremors were reduced by acute and chronic dopaminergic treatments (p \u3c 0.01) but not by alcohol or primidone. Tremor occurs commonly in DLB patients with a complex mixed tremor pattern which shows a significant response to acute and chronic dopaminergic treatments. Recognizing that there is a clinical category of tremulous DLB may help the differential diagnosis of tremors. Electronic supplementary material The online version of this article (doi:10.1007/s00415-013-6853-y) contains supplementary material, which is available to authorized users

Time for a European initiative for research to prevent cancer: A manifesto for Cancer Prevention Europe (CPE)

A landmark resolution on cancer prevention and control was adopted by Member States at the World Health Assembly 2017, noting that “risk reduction has the potential to prevent around half of all cancers” and urging “to promote cancer research to improve the evidence base for cancer prevention and control”. Public health oriented strategies for cancer prevention and their optimal application in effective real-life programmes will be vital to circumvent the dramatic health and economic implications of a strategy and healthcare expenditure based primarily on cancer treatment. The inter-disciplinary nature of cancer prevention stretches from the sub-microscopic study of cancer pathways through to the supra-macroscopic analysis of the “causes of the causes”, encompassing socio-economic and environmental factors. Research is required to provide new evidence-based preventive interventions and to understand the factors that hamper their implementation within health care systems and in the community. Successful implementation of cancer prevention requires long-term vision, a dedicated research agenda and funding, sustainable infrastructure and cooperation between countries and programmes. In order to develop world class prevention research in Europe that translates into effective cancer prevention guidelines and policies, we report on the creation of Cancer Prevention Europe. This international and multidisciplinary consortium of research institutes, organisations and networks of excellence with a common mission of reducing cancer morbidity and mortality in European populations through prevention, brings together different fields of expertise, from laboratory science through to policy research, as well as dissemination of the best evidence, the best quality indicators and the best practices used

Contribution of MUTYH variants to male breast cancer risk: results from a multicenter study in Italy

Inherited mutations in BRCA1, and, mainly, BRCA2 genes are associated with increased risk of male breast cancer (MBC). Mutations in PALB2 and CHEK2 genes may also increase MBC risk. Overall, these genes are functionally linked to DNA repair pathways, highlighting the central role of genome maintenance in MBC genetic predisposition. MUTYH is a DNA repair gene whose biallelic germline variants cause MUTYH-associated polyposis (MAP) syndrome. Monoallelic MUTYH variants have been reported in families with both colorectal and breast cancer and there is some evidence on increased breast cancer risk in women with monoallelic variants. In this study, we aimed to investigate whether MUTYH germline variants may contribute to MBC susceptibility. To this aim, we screened the entire coding region of MUTYH in 503 BRCA1/2 mutation negative MBC cases by multigene panel analysis. Moreover, we genotyped selected variants, including p.Tyr179Cys, p.Gly396Asp, p.Arg245His, p.Gly264Trpfs*7, and p.Gln338His, in a total of 560 MBC cases and 1,540 male controls. Biallelic MUTYH pathogenic variants (p.Tyr179Cys/p.Arg241Trp) were identified in one MBC patient with phenotypic manifestation of adenomatous polyposis. Monoallelic pathogenic variants were identified in 14 (2.5%) MBC patients, in particular, p.Tyr179Cys was detected in seven cases, p.Gly396Asp in five cases, p.Arg245His and p.Gly264Trpfs*7 in one case each. The majority of MBC cases with MUTYH pathogenic variants had family history of cancer including breast, colorectal, and gastric cancers. In the case-control study, an association between the variant p.Tyr179Cys and increased MBC risk emerged by multivariate analysis [odds ratio (OR) = 4.54; 95% confidence interval (CI): 1.17-17.58; p = 0.028]. Overall, our study suggests that MUTYH pathogenic variants may have a role in MBC and, in particular, the p.Tyr179Cys variant may be a low/moderate penetrance risk allele for MBC. Moreover, our results suggest that MBC may be part of the tumor spectrum associated with MAP syndrome, with implication in the clinical management of patients and their relatives. Large-scale collaborative studies are needed to validate these findings

Cancer Prevention Europe

The case for cancer prevention in Europe is the same as for all other parts of the world. The number of cancers is increasing, driven by demographic change and evolution in the exposure to risk factors, while the cost of treating patients is likewise spiralling. Estimations suggest that around 40% of cancers in Europe could be prevented if current understanding of risk and protective factors was translated into effective primary prevention, with further reductions in cancer incidence and mortality by screening, other approaches to early detection, and potentially medical prevention. However, the infrastructure for cancer prevention tends to be fragmented between and within different countries in Europe. This lack of a coordinated approach recently led to the foundation of Cancer Prevention Europe (Forman et al., 2018), a collaborative network with the main aims of strengthening cancer prevention in Europe by increasing awareness of the needs, the associated required resources and reducing inequalities in access to cancer prevention across Europe. This article showcases the need for strengthening cancer prevention and introduces the objectives of Cancer Prevention Europe and its foreseen future role in reducing the European cancer burden.</p

Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II) : an international, double-blind, randomised placebo-controlled trial

This study was funded by Cancer Research UK (C569/A5032), the National Health and Medical Research Council Australia (GNT300755, GNT569213), Sanofi-Aventis, and AstraZeneca. Sanofi-Aventis and AstraZeneca provided anastrozole and matching placebo. The study sponsor was Queen Mary University of London.Peer reviewedPublisher PD

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

Gender differences in outcomes after left atrial appendage closure with Watchman FLX device: insights from the Italian-FLX registry

IntroductionRecent studies have shown gender differences in cardiovascular outcomes after left atrial appendage closure (LAAC), highlighting different complication rates and adverse events, particularly in short-term assessments. As a result, there remains a significant knowledge gap on how these differences directly impact the efficacy and safety of LAAC procedures. The aim of this retrospective study was to investigate the clinical outcomes of LAAC in women and men using the Watchman FLX device.MethodsThis retrospective, multicenter study analyzes gender-specific outcomes in 650 patients who underwent LAAC with the Watchman FLX device between March 2019 and May 2022, drawn from the ITALIAN-FLX registry.ResultsThe results show comparable rates of all-cause mortality, stroke, transient ischemic attack and major bleeding in men and women 12 months after the procedure. Notably, no significant gender differences were found for periprocedural complications.ConclusionIn conclusion, this study shows that LAAC with the Watchman FLX device has comparable clinical outcomes between genders at both short-term and long-term follow-up