Mammographic breast density (MBD) is a strong independent risk factor for breast cancer (BC). We designed a matched case-case study in the EPIC Florence cohort, to evaluate possible associations ...between the pre-diagnostic metabolomic profile and the risk of BC in high- versus low-MBD women who developed BC during the follow-up. A case-case design with 100 low-MBD (MBD ≤ 25%) and 100 high-MDB BC cases (MBD > 50%) was performed. Matching variables included age, year and type of mammographic examination.
H NMR metabolomic spectra were available for 87 complete case-case sets. The conditional logistic analyses showed an inverse association between serum levels of alanine, leucine, tyrosine, valine, lactic acid, pyruvic acid, triglycerides lipid main fraction and 11 VLDL lipid subfractions and high-MBD cases. Acetic acid was directly associated with high-MBD cases. In models adjusted for confounding variables, tyrosine remained inversely associated with high-MBD cases while 3 VLDL subfractions of free cholesterol emerged as directly associated with high-MBD cases. A pathway analysis showed that the "phenylalanine, tyrosine and tryptophan pathway" emerged and persisted after applying the FDR procedure. The supervised OPLS-DA analysis revealed a slight but significant separation between high- and low-MBD cases. This case-case study suggested a possible role for pre-diagnostic levels of tyrosine in modulating the risk of BC in high- versus low-MBD women. Moreover, some differences emerged in the pre-diagnostic concentration of other metabolites as well in the metabolomic fingerprints among the two groups of patients.
Objectives
To report and analyse the characteristics and performance of the first cohort of Italian radiologists completing the national mammography self-evaluation online test established by the ...Italian Society of Medical Radiology (SIRM).
Methods
A specifically-built dataset of 132 mammograms (24 with screen-detected cancers and 108 negative cases) was preliminarily tested on 48 radiologists to define pass thresholds (62% sensitivity and 86% specificity) and subsequently made available online to SIRM members during a 13-month timeframe between 2018 and 2019. Associations between participants’ characteristics, pass rates, and diagnostic accuracy were then investigated with descriptive statistics and univariate and multivariable regression analyses.
Results
A total of 342 radiologists completed the test, 151/342 (44.2%) with success. All individual variables, except gender, showed a significant correlation with pass rates and diagnostic sensitivity, confirmed by univariate logistic regression, while only involvement in organised screening programs and number of mammograms read per year showed a positive association with specificity at univariate logistic regression. In the multivariable regression analysis, fewer variables remained significant: > 3000 mammograms read per year for success rate; female gender, public practice setting, and higher experience self-judgement for sensitivity; no variables were significantly associated with specificity.
Conclusions
This national self-evaluation test effectively differentiated multiple aspects of mammographic reading experience, but specific breast imaging experience was shown not to strictly guarantee good diagnostic accuracy. Due to its easy use and the validity of obtained results, this test could be extended to all Italian breast radiologists, regardless of their experience, also as a Breast Unit accreditation criterion.
Key Points
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This self-evaluation test was found to be able to differentiate various degrees of mammographic interpretation experience.
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Breast cancer screening readers should undergo a self-assessment test, since experience parameters alone do not guarantee diagnostic ability.
Purpose
Mammographic breast density (MBD) is a marker of increased breast cancer (BC) risk, yet much remains to be clarified about the underlying mechanisms. We investigated whether DNA methylation ...patterns differ between high- vs. low-MBD women who developed BC during an 8.9-year median follow-up in the Florence section of the European Prospective Investigation into Cancer and Nutrition.
Methods
We analysed 96 pairs of women with BC arising on high- vs. low-MBD breasts (BI-RADS category III–IV vs. I). DNA methylation was determined on pre-diagnostic blood samples using the Illumina Infinium MethylationEPIC BeadChip assay. The statistical analysis was conducted by performing an epigenome-wide association study (EWAS), by searching differentially methylated regions (DMRs) in gene promoters (followed by functional enrichment and gene annotation analysis); and through a “candidate pathways” approach focusing on pre-defined inflammation-related pathways.
Results
In EWAS, no single CpG site was differentially methylated between high- and low-MBD women after correction for multiple testing. A total of 140 DMRs were identified, of which 131 were hyper- and 9 hypo-methylated amongst high-MBD women. These DMRs encompassed an annotation cluster of 35 genes coding for proteins implicated in transcription regulation and DNA binding. The “apoptosis signalling” was the only inflammation-related candidate pathway differentially methylated between high- and low-MBD women.
Conclusion
Pre-diagnostic methylation patterns differ between high- vs. low-MBD women who subsequently develop BC, particularly, in genes involved in the regulation of DNA transcription and cell apoptosis. Our study provides novel clues about the mechanisms linking MBD and BC.
Purpose
Several studies in recent years have investigated the relationship between alcohol intake and melanoma risk, with conflicting results. To help clarify this issue, we conducted a literature ...review and dose–response meta-analysis of studies published until June 30th, 2017, that examined the association between alcohol intake (overall and by beverage type) and melanoma risk.
Methods
We used random effect models with maximum likelihood estimation to calculate summary relative risk (SRR) and 95% confidence intervals (95%CI).
Results
We included 20 independent studies (encompassing 10,555 melanoma cases and over 1.6 million non-cases/controls) published during 1986–2016, of which six had a prospective cohort study design. Adjustment for phenotypic characteristics and sunlight exposure was performed in 11 and nine studies, respectively. Alcohol intake was moderately associated with melanoma risk: the SRR were 1.29 (95% CI 1.14–1.45) for those in the highest vs. lowest category of current alcohol intake, and 1.96 (95% CI 1.02–3.76,
I
2
= 0%) for cumulative intake. In the dose–response analysis, the increase in risk associated with a 10 g increment in daily alcohol intake was 1.07 (95% CI 1.03–1.11). Risk estimates did not differ by gender, study design and adjustment for confounders; between-studies heterogeneity was acceptable, and there was no evidence of publication bias.
Conclusions
Our findings suggest that alcohol drinking may be moderately associated with increased melanoma risk, although residual confounding and bias cannot be ruled out. Further research is needed to confirm these findings, clarify the role of the different alcohol sources, and investigate the interaction with known melanoma risk factors.
We aimed to provide a comprehensive overview of the link between vitamin D and non-melanoma skin cancer (NMSC). For this purpose, we conducted a systematic literature review (updated to 3 February ...2021) and meta-analysis of the studies reporting on the association between vitamin D intake (from diet and supplements) and blood concentration, polymorphisms of the vitamin D receptor (VDR) and vitamin D binding protein (VDBP) genes, and the risk of NMSC. Random effects meta-analysis models were fitted to merge study-specific risk estimates into summary relative risk (SRR) and corresponding 95% confidence intervals (CI). Twenty-four studies altogether were included. There was a suggestive association between increasing serum/plasma vitamin D concentration and NMSC risk (SRR for highest vs. lowest concentration 1.67, 95%CI 0.61–4.56), although with large heterogeneity across studies (I2 = 91%). NMSC risk was associated with highest vitamin D intake in observational studies but not in clinical trials. Finally, there was no significant association between any polymorphism of the VDR and VDBP genes and NMSC risk. In conclusion, no strong relationship between vitamin D metabolism and NMSC risk appears to exist according to our systematic review and meta-analysis, although some findings are worthy of further investigation.
Distinguishing between epithelioid peritoneal mesothelioma and papillary serous carcinomas involving the peritoneum may be very difficult, owing to overlapping morphologic features. ...Immunohistochemistry may facilitate establishing a correct diagnosis, but, as no single antibody has demonstrated absolute sensitivity and specificity for either mesothelioma or serous carcinoma, the differential diagnosis is based mainly on the combined use of several markers. The purpose of this study was to ascertain the sensitivity and specificity of a series of mesothelial markers including more recently investigated antigens such as h-caldesmon (h-CD) and D2-40 and, using receiver operating characteristic curve analysis, to identify a selected appropriate panel of antibodies for differentiating between epithelioid peritoneal mesothelioma and serous papillary carcinoma of the ovary. Fifteen cases of epithelioid peritoneal mesothelioma and 40 cases of papillary serous carcinoma of the ovary (25 primary and 15 metastatic to the peritoneum) were immunostained for h-CD, D2-40, calretinin, cytokeratin 5/6, thrombomodulin, estrogen and progesterone receptors (ER and PR), Ber-EP4, B72.3, CA19-9, and CD15. h-CD and calretinin showed the highest sensitivity (100%), followed by D2-40 (93.3%) and cytokeratin 5/6 (93.3%); thrombomodulin had the lowest sensitivity (60%). h-CD and thrombomodulin had the best specificity (95%) for mesothelioma, followed by calretinin (87.5%), D2-40 (80%), and cytokeratin 5/6 (72.5%). Among carcinoma markers, ER and Ber-EP4 demonstrated the highest sensitivity (95%) followed by B72.3 (72.5%), PR (65%), CA19.9 (60%), and CD15 (45%). The specificity of the nonmesothelial markers was 100%, except for Ber-EP4 (93.3%). The relationship between the values of sensitivity and specificity of each marker using receiver operating characteristic analysis permitted the identification of h-CD, calretinin, ER, and Ber-EP4 as the markers with the best performance in differentiating epithelioid peritoneal mesothelioma from serous papillary carcinoma of the ovary.
Cigarette smoking has been recognized as a risk factor for breast cancer (BC) also if the biological mechanism remains poorly understood. High mammographic breast density (MBD) is associated with BC ...risk and many BC risk factors, such as genetic, anthropometric, reproductive and lifestyle factors and age, are also able to modulate MBD. The aim of the present study was to prospectively explore, in post-menopausal women, the association between smoking habits and MBD, assessed using an automated software, considering duration and intensity of smoking.
The analysis was carried out in 3,774 women enrolled in the European Prospective Investigation into Cancer and Nutrition (EPIC) Florence cohort in 1993-98, participating in the 2004-06 follow up (FU) and with at least one full-field digital mammography (FFDM) performed after FU. For each woman, detailed information on smoking habits, anthropometry, lifestyle and reproductive history was collected at enrollment and at FU. Smoking information at baseline and at FU was integrated. The fully automated Volpara™ software was used to obtain total breast volume (cm
), absolute breast dense volume (DV, cm
) and volumetric percent density (VPD, %) from the first available FFDM (average 5.3 years from FU). Multivariable linear regression models were applied to evaluate the associations between smoking habits and VPD or DV.
An inverse association between smoking exposure and VPD emerged (Diff% -7.96%, p <0.0001 for current smokers and -3.92%, p 0.01 for former smokers, compared with non-smokers). An inverse dose-response relationship with number of cigarettes/day, years of smoking duration and lifetime smoking exposure (pack-years) and a direct association with time since smoking cessation among former smokers emerged. Similar associations, with an attenuated effect, emerged when DV was considered as the outcome variable.
This longitudinal study confirms the inverse association between active smoking, a known risk factor for BC, and MBD among post-menopausal women. The inclusion of smoking habits in the existing BC risk prediction models could be evaluated in future studies.
The relationship between coffee consumption and coronary heart disease (CHD) has been investigated in several studies with discrepant results. We examined the association between Italian-style ...(espresso and mocha) coffee consumption and CHD risk.
We investigated 12,800 men and 30,449 women without history of cardiovascular disease recruited to the EPICOR prospective cohort study. Coffee consumption was assessed at baseline. In a random sub-cohort of 1472 subjects, plasma triglycerides, and total, LDL and HDL cholesterol were determined to investigate the effect of coffee consumption on plasma lipids.
After a mean follow up of 10.9 years, 804 cases of CHD (500 acute events, 56 fatal events and 248 revascularizations, all first events) were identified. Multivariable adjusted hazard ratios for CHD were: 1.18 (95% CI 0.87-1.60) for drinking 1-2 cups/day, 1.37 (95% CI 1.03-1.82) for >2-4 cups/day and 1.52 (95% CI 1.11-2.07) for over 4 cups/day (P trend <0.001) compared to reference (<1 cup/day). Plasma triglycerides, and total, LDL and HDL cholesterol did not vary significantly (ANOVA) with coffee consumption.
Consumption of over 2 cups/day of Italian-style coffee is associated with increased CHD risk, but coffee consumption was not associated with plasma lipid changes, so the adverse effect of consumption appears unrelated to lipid profile.
Metastatic castration-resistant prostate cancer remains a challenging condition to treat. Among the available therapeutic options, the androgen receptor signaling inhibitors abiraterone acetate plus ...prednisone (AA) and enzalutamide (Enza), are currently the most used first-line therapies in clinical practice. However, validated clinical indicators of prognosis in this setting are still lacking. In this study, we aimed to evaluate a prognostic model based on the time of metastatic disease presentation (after prior local therapy PLT or de-novo DN) and disease burden (low volume LV or high-volume HV) at AA/Enza onset for mCRPC patients receiving either AA or Enza as first-line.
A cohort of consecutive patients who started AA or Enza as first-line treatment for mCRPC between January 1st, 2015, and April 1st, 2019 was identified from the clinical and electronic registries of the 9 American and European participating centers. Patients were classified into 4 cohorts by the time of metastatic disease presentation (PLT or DN) and volume of disease (LV or HV; per the E3805 trial, HV was defined as the presence of visceral metastases and/or at least 4 bone metastases of which at least 1 out the axial/pelvic skeleton) at AA/Enza onset. The endpoint was overall survival defined as the time from AA or Enza initiation, respectively, to death from any cause or censored at the last follow-up visit, whichever occurred first.
Of the 417 eligible patients identified, 157 (37.6%) had LV/PLT, 87 (20.9%) LV/DN, 64 (15.3%) HV/PLT, and 109 (26.1%) HV/DN. LV cohorts showed improved median overall survival (59.0 months; 95% CI, 51.0-66.9 months) vs. HV cohorts (27.5 months; 95% CI, 22.8-32.2 months; P = 0.0001), regardless of the time of metastatic presentation. In multivariate analysis, HV cohorts were confirmed associated with worse prognosis compared to those with LV (HV/PLT, HR = 1.87; p = 0.029; HV/DN, HR = 2.19; P = 0.002).
Our analysis suggests that the volume of disease could be a prognostic factor for patients starting AA or Enza as first-line treatment for metastatic castration-resistant prostate cancer, pending prospective clinical trial validation.
Published evidence suggests that immunonutrition has the potential to decrease postoperative complications and reduce length of stay in patients undergoing surgery for colorectal cancer. However, ...only a few studies have analyzed the effects of immunonutrition on tumor microenvironment and evaluated its prognostic impact.
This is a single center retrospective study enrolling 50 patients undergoing elective surgery for colorectal cancer managed with immunonutrition and 50 patients managed with standard nutrition for comparison. Tumor microenvironment was analyzed before (on the biopsy at the time of diagnosis) and after (on the matched surgical specimen) administration of immunonutrition. Immune function related indicators, including cytotoxic T-lymphocytes, helper T-cells, antigen presenting cells, natural killer cells, T-exhausted lymphocytes, T-regulatory cells, M1 and M2 tumor associated macrophages and PD-L1 expression were assessed by immunohistochemistry. For both groups, clinicopathological data were collected and a 5-year follow-up was available.
We found that immunonutrition significantly activated the T-cell response against cancer, alter tumor microenvironment phenotype towards M2 polarization and inhibits the PD1/PD-L1 axis. A lower rate of postoperative complications and a shorter length of stay (
= 0.04) were observed in the immune nutrition group. Compared to standard nutrition group, patients managed wit immune nutrition showed a higher 5-year overall survival (
= 0.001). Finally, immune nutrition allowed to reduce the hospital care costs.
Immunonutrition modulates tumor microenvironment by improving immune function and could prolong survival in patients undergoing elective surgery for colorectal cancer. Further studies are needed to optimize IN protocols and confirm their prognostic impact.
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