Metabolically defined body size and body shape phenotypes and risk of postmenopausal breast cancer in the European Prospective Investigation into Cancer and Nutrition.

BACKGROUND: Excess body fatness and hyperinsulinemia are both associated with an increased risk of postmenopausal breast cancer. However, whether women with high body fatness but normal insulin levels or those with normal body fatness and high levels of insulin are at elevated risk of breast cancer is not known. We investigated the associations of metabolically defined body size and shape phenotypes with the risk of postmenopausal breast cancer in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition. METHODS: Concentrations of C-peptide-a marker for insulin secretion-were measured at inclusion prior to cancer diagnosis in serum from 610 incident postmenopausal breast cancer cases and 1130 matched controls. C-peptide concentrations among the control participants were used to define metabolically healthy (MH; in first tertile) and metabolically unhealthy (MU; >1st tertile) status. We created four metabolic health/body size phenotype categories by combining the metabolic health definitions with normal weight (NW; BMI < 25 kg/m2 , or WC < 80 cm, or WHR < 0.8) and overweight or obese (OW/OB; BMI ≥ 25 kg/m2 , or WC ≥ 80 cm, or WHR ≥ 0.8) status for each of the three anthropometric measures separately: (1) MHNW, (2) MHOW/OB, (3) MUNW, and (4) MUOW/OB. Conditional logistic regression was used to compute odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Women classified as MUOW/OB were at higher risk of postmenopausal breast cancer compared to MHNW women considering BMI (OR = 1.58, 95% CI = 1.14-2.19) and WC (OR = 1.51, 95% CI = 1.09-2.08) cut points and there was also a suggestive increased risk for the WHR (OR = 1.29, 95% CI = 0.94-1.77) definition. Conversely, women with the MHOW/OB and MUNW were not at statistically significant elevated risk of postmenopausal breast cancer risk compared to MHNW women. CONCLUSION: These findings suggest that being overweight or obese and metabolically unhealthy raises risk of postmenopausal breast cancer while overweight or obese women with normal insulin levels are not at higher risk. Additional research should consider the combined utility of anthropometric measures with metabolic parameters in predicting breast cancer risk.

Antisenescence effect of REAC biomodulation to counteract the evolution of myelodysplastic syndrome.

About 30 percent of patients diagnosed with myelodysplastic syndromes (MDS) progress to acute myeloid leukemia (AML). The senescence of bone marrow?derived mesenchymal stem cells (BMSCs) seems to be one of the determining factors in inducing this drift. Research is continuously looking for new methodologies and technologies that can use bioelectric signals to act on senescence and cell differentiation towards the phenotype of interest. The Radio Electric Asymmetric Conveyer (REAC) technology, aimed at reorganizing the endogenous bioelectric activity, has already shown to be able to determine direct cell reprogramming effects and counteract the senescence mechanisms in stem cells. Aim of the present study was to prove if the anti-senescence results previously obtained in different kind of stem cells with the REAC Tissue optimization - regenerative (TO-RGN) treatment, could also be observed in BMSCs, evaluating cell viability, telomerase activity, p19ARF, P21, P53, and hTERT gene expression. The results show that the REAC TO-RGN treatment may be a useful tool to counteract the BMSCs senescence which can be the basis of AML drift. Nevertheless, further clinical studies on humans are needed to confirm this hypothesis.

Aesthetic results following breast cancer surgery: A prospective study on 6515 cases from ten Italian Senonetwork breast centers.

Breast cancer treatment has deeply changed in the last decades, since clinical and oncological cure cannot be achieved without patient's satisfaction in term of aesthetic outcomes. Several methods have been proposed to objectively assess these results. However, Italian breast centers have not yet agreed on measurable, reproducible and validated aesthetic outcome indicators to monitor their performance. METHODS: The study was designed and conducted by Senonetwork, a not-for-profit association of Italian breast centers. Ten breast centers were selected based on specific eligibility criteria. This multicentre observational prospective study recruited 6515 patients with diagnosis of in situ or invasive breast cancer who underwent breast surgery in the years 2013-2016. Thirteen indicators of aesthetic results and of related quality of care were analyzed. Data collection and analysis were conducted using a common study database. RESULTS: On average, seven out of ten centers were able to collect data on the proposed indicators with a proportion of missing values < 25%. By expert consensus based on study results, some seven indicators have been defined as "mandatory" while the remaining six have been defined as "recommended" because they require further refinement before they can be proposed for monitoring aesthetic outcomes or because there are doubts on the feasibility of data collection. The minimum standard is reached for 5 of 13 indicators. This finding and the wide range between centers reveal that there is ample room for improvement. CONCLUSIONS: From the present study useful measurable aesthetic parameters have emerged, leading to the definition of target objectives that breast centers can use for benchmarking and improvement of quality of care.

Overview on surgical management of papillary thyroid microcarcinoma.

Particular interest is now being given to the best treatment of papillary thyroid microcarcinoma (PTMC) due to its significantly increased incidence. PTMC typically shows indolent organic behavior but, in a low percentage of cases, it can express a relative aggressive behavior. Several risk factors have been shown to negatively influence the rate of regional recurrences and metastases such as tumor diameter, Romaage, sex, multifocality, capsular invasion, extracellular diffusion, lymph node metastases, histological variants, mutated Braf and incidentality. The identification of patients with aggressive PTMCs among the majority with low risk lesions is very important to plan an adequate clinical management, thus the most appropriate surgical treatment. The latter includes thyroid lobectomy and total thyroidectomy with central compartment lymphadenectomy, though several studies did not show statistically significant differences in terms of recurrence and mortality rates between the two techniques. At last, it seems crucial to better define those biological features able to improve selection making process of patients with PTMCs aiming to reserve more radical surgery to those patients carrying more aggressive clinicopathologic features and worse prognosis.

Prevalence of comorbidities in women with and without breast cancer in Soweto, South Africa: Results from the SABC study.

BACKGROUND: Comorbidities occurring concurrently in breast cancer patients can be burdensome, as they may negatively influence time and stage of presentation. OBJECTIVES: To describe the comorbid health conditions among South African (SA) black women with and without breast cancer and to determine factors associated with advanced-stage presentation of breast cancer. METHODS: A population-based case-control study on breast cancer was conducted in black women in Soweto, SA, the SABC (South Africa Breast Cancer) study. Lifestyle information and blood samples were collected from 399 women with histologically confirmed new cases of invasive primary breast cancer, recruited prior to any therapy, and 399 age- and neighbourhood-matched controls without breast cancer. We compared self-reported metabolic diseases, depression, anthropometric measurements, blood pressure, HIV status and point-of-care lipid and glucose levels between patients with breast cancer and the control group. RESULTS: In the whole population, the mean (standard deviation) age was 54.6 (12.9) years, the majority (81.2%) of the participants were overweight or obese, 85.3% had abdominal adiposity, 61.3% were hypertensive, 47.1% had impaired fasting plasma glucose, 8.4% had elevated total cholesterol, 74.8% had low high-density lipoprotein and 10.9% were assessed to be depressed. Ninety-one percent of the whole cohort had at least one metabolic disease. In the breast cancer group, 72.2% had one or more metabolic diseases only (HIV-negative and no evidence of depression), compared with 64.7% of the control group. From a multivariate logistic regression adjusted model, higher household socioeconomic status conferred a 19% reduction in the odds of having advanced-stage breast cancer at diagnosis, while hypertension, dyslipidaemia and HIV were not significantly associated with stage at breast cancer diagnosis in the adjusted model. CONCLUSIONS: A large proportion of women experience several comorbidities, highlighting the need to address the chronic non-communicable disease epidemic in SA and to co-ordinate multidisciplinary primary-, secondary- and tertiary-level care in the country's complex healthcare system for better outcome.

The prognostic and predictive role of hyponatremia in patients with advanced non-small cell lung cancer (NSCLC) with bone metastases.

PURPOSE: Hyponatremia and bone metastasis (BMs) are known as negative prognostic factors in patients affected by metastatic non-small cell lung cancer (NSCLC). Hyponatremia is associated with higher risk of osteoporosis and bone fracture, but no data are available about the relationship between hyponatremia and bone metastasis. This study aims to analyze the prognostic impact of hyponatremia in NSCLC patients with bone metastases. METHODS: We retrospectively collected data about advanced NSCLC patients. Survival curves were estimated using Kaplan-Meier method, and comparisons were made using chi-square test. RESULTS: Six hundred forty-seven patients were enrolled into the study. BMs were present in 264 patients (41%) at diagnosis, while hyponatremia appeared in 237 (37%) patients during the first-line treatment. Patients without BMs had a median overall survival (mOS) of 15.9 months (95% CI 14.1-17.9) versus 11.4 months (95% CI 9.4-13.4) for patients with BMs (p = 0.001). Eunatremic patients had a better outcome (mOS 16.3 months, 95% CI 14.6-18.0 vs 10.3 months, 95% I 7.6-12.8, p = 0.003). Considering the two variables, patients with BMs and hyponatremia had a mOS of 10.1 months (95% CI 4.3-15.9), patients with hyponatremia without BMs 11.9 months (95% CI 11.4-12.4), while mOS was 13.1 months (95% CI 12.0-14.2) for eunatremic patients with BMs versus 17.1 months (95% CI 15.2-19.1) in eunatremic patients without BMs (p = 0.0020). Hyponatremic patients developed metachronous BMs significantly earlier (3.73 vs 5.76 months, p = 0.0187). CONCLUSIONS: Our study showed that hyponatremia is an important prognostic factor and it should be necessarily considered to enhance the management of NSCLC patients with BMs.

A prospective evaluation of plasma phospholipid fatty acids and breast cancer risk in the EPIC study.

BACKGROUND: Intakes of specific fatty acids have been postulated to impact breast cancer risk but epidemiological data based on dietary questionnaires remain conflicting. MATERIALS AND METHODS: We assessed the association between plasma phospholipid fatty acids and breast cancer risk in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition study. Sixty fatty acids were measured by gas chromatography in pre-diagnostic plasma phospholipids from 2982 incident breast cancer cases matched to 2982 controls. Conditional logistic regression models were used to estimate relative risk of breast cancer by fatty acid level. The false discovery rate (q values) was computed to control for multiple comparisons. Subgroup analyses were carried out by estrogen receptor (ER) and progesterone receptor expression in the tumours. RESULTS: A high level of palmitoleic acid [odds ratio (OR) for the highest quartile compared with the lowest OR (Q4-Q1) 1.37; 95% confidence interval (CI), 1.14-1.64; P for trend = 0.0001, q value = 0.004] as well as a high desaturation index (DI16) (16:1n-7/16:0) [OR (Q4-Q1), 1.28; 95% C, 1.07-1.54; P for trend = 0.002, q value = 0.037], as biomarkers of de novo lipogenesis, were significantly associated with increased risk of breast cancer. Levels of industrial trans-fatty acids were positively associated with ER-negative tumours [OR for the highest tertile compared with the lowest (T3-T1)=2.01; 95% CI, 1.03-3.90; P for trend = 0.047], whereas no association was found for ER-positive tumours (P-heterogeneity =0.01). No significant association was found between n-3 polyunsaturated fatty acids and breast cancer risk, overall or by hormonal receptor. CONCLUSION: These findings suggest that increased de novo lipogenesis, acting through increased synthesis of palmitoleic acid, could be a relevant metabolic pathway for breast tumourigenesis. Dietary trans-fatty acids derived from industrial processes may specifically increase ER-negative breast cancer risk.

Circulating leptin and adiponectin, and breast density in premenopausal Mexican women: the Mexican Teachers' Cohort.

PURPOSE: Leptin and adiponectin are produced by the adipose tissue. Mammographic density (MD) is one of the strongest predictors of breast cancer (BC) and is highly influenced by adiposity. How the interplay between MD, obesity, and obesity-related biomarkers influences BC risk, however, is still unknown, especially in premenopausal women, where adiposity seems to be protective for BC. The aim of the present study was to explore the association between circulating leptin, adiponectin, and their ratio, with MD in Mexican premenopausal women who are part of the large Mexican Teachers' Cohort (MTC). METHODS: A subsample of 2,084 women from the MTC participated in a clinical evaluation. Of them, 574 premenopausal women were randomly selected, from four MD strata. Serum leptin and adiponectin concentrations were measured by immunoassays. Multivariate regression analyses were performed to compare means of MD by quartiles of adipokines and their ratio. RESULTS: High leptin and leptin/adiponectin ratio levels were significantly associated with lower percentage MD and higher absolute and non-absolute dense tissue areas. High adiponectin levels were significantly associated with lower absolute dense and non-dense tissue areas, but not with percentage MD. After adjustment for BMI, only the associations between percentage MD and absolute non-dense tissue area with leptin remained statistically significant. CONCLUSIONS: Leptin, adiponectin, and their ratio were associated with MD; however, only the positive association with leptin seemed to be independent from overall obesity.

Plasma concentrations and intakes of amino acids in male meat-eaters, fish-eaters, vegetarians and vegans: a cross-sectional analysis in the EPIC-Oxford cohort.

BACKGROUND/OBJECTIVES: We aimed to investigate the differences in plasma concentrations and in intakes of amino acids between male meat-eaters, fish-eaters, vegetarians and vegans in the Oxford arm of the European Prospective Investigation into Cancer and Nutrition. SUBJECTS/METHODS: This cross-sectional analysis included 392 men, aged 30-49 years. Plasma amino acid concentrations were measured with a targeted metabolomic approach using mass spectrometry, and dietary intake was assessed using a food frequency questionnaire. Differences between diet groups in mean plasma concentrations and intakes of amino acids were examined using analysis of variance, controlling for potential confounding factors and multiple testing. RESULTS: In plasma, concentrations of 6 out of 21 amino acids varied significantly by diet group, with differences of -13% to +16% between meat-eaters and vegans. Concentrations of methionine, tryptophan and tyrosine were highest in fish-eaters and vegetarians, followed by meat-eaters, and lowest in vegans. A broadly similar pattern was seen for lysine, whereas alanine concentration was highest in fish-eaters and lowest in meat-eaters. For glycine, vegans had the highest concentration and meat-eaters the lowest. Intakes of all 18 dietary amino acids differed by diet group; for the majority of these, intake was highest in meat-eaters followed by fish-eaters, then vegetarians and lowest in vegans (up to 47% lower than in meat-eaters). CONCLUSIONS: Men belonging to different habitual diet groups have significantly different plasma concentrations of lysine, methionine, tryptophan, alanine, glycine and tyrosine. However, the differences in plasma concentrations were less marked than and did not necessarily mirror those seen for amino acid intakes.

Hyponatremia is a predictor of hospital length and cost of stay and outcome in cancer patients.

PURPOSE: Hyponatremia is the most common electrolyte disorder in hospitalized patients, and it might be an indicator of poor prognosis and might have negative effects on hospitalization length and quality of life in non-malignant as well as in malignant diseases. The aim of this study is to determine the impact of hyponatremia on the length and on the cost of hospitalization as well as on outcome in cancer patients. METHODS: The present study includes 105 consecutive cancer patients hospitalized at our institution from June 2013 to December 2013. Data regarding age, sex, staging, histology, chemotherapy, and serum sodium levels at admission, during hospitalization, and at discharge were recorded and statistically analyzed. Impact of hyponatremia on length and cost of hospitalization and on outcome was evaluated. RESULTS: A significant difference in overall survival since the date of admission was observed between eunatremic and hyponatremic patients (p = 0.0255). A statistically significant correlation was also found between the length of stay and the detection of hyponatremia. At multivariate analysis, hyponatremia at admission, severity of hyponatremia, and stage of disease resulted independent prognostic factors. Furthermore, a patient with moderate or severe hyponatremia cost, in rate terms, 128 and 299 % more than a normonatremic patient, respectively. CONCLUSIONS: The occurrence of hyponatremia at the admission or during the hospitalization may represent a significant factor influencing the outcome and the length of hospitalization. Acting effective and timely on the normalization of sodium levels might have a positive effect on prognosis in this setting of patients, as well as on the length of stay in hospital, thus potentially resulting in savings.

15-epi-lipoxin A4 reduces the mortality of prematurely born pups in a mouse model of infection-induced preterm birth.

Preterm birth remains the leading cause of neonatal mortality and morbidity worldwide. There are currently few effective therapies and therefore an urgent need for novel treatments. Although there is much focus on trying to alter gestation of delivery, the primary aim of preterm birth prevention therapies should be to reduce prematurity related mortality and morbidity. Given the link between intrauterine infection and inflammation and preterm labour (PTL), we hypothesized that administration of lipoxins, key anti-inflammatory and pro-resolution mediators, could be a useful novel treatment for PTL. Using a mouse model of infection-induced PTL, we investigated whether 15-epi-lipoxin A4 could delay lipopolysaccharide (LPS)-induced PTL and reduce pup mortality. On D17 of gestation mice (n = 9-12) were pretreated with vehicle or 15-epi-lipoxin A4 prior to intrauterine administration of LPS or PBS. Although pretreatment with 15-epi-lipoxin A4 did not delay LPS-induced PTL, there was a significant reduction in the mortality amongst prematurely delivered pups (defined as delivery within 36 h of surgery) in mice treated with 15-epi-lipoxin A4 prior to LPS treatment, compared with those receiving LPS alone (P < 0.05). Quantitative real-time (QRT)-PCR analysis of utero-placental tissues harvested 6 h post-treatment demonstrated that 15-epi-lipoxin A4 treatment increased Ptgs2 expression in the uterus, placenta and fetal membranes (P < 0.05) and decreased 15-Hpgd expression (P < 0.05) in the placenta and uterus, suggesting that 15-epi-lipoxin A4 may regulate the local production and activity of prostaglandins. These data suggest that augmenting lipoxin levels could be a useful novel therapeutic option in the treatment of PTL, protecting the fetus from the adverse effects of infection-induced preterm birth.

Insulin-like growth factor I and risk of epithelial invasive ovarian cancer by tumour characteristics: results from the EPIC cohort.

BACKGROUND: Prospective studies on insulin-like growth factor I (IGF-I) and epithelial ovarian cancer (EOC) risk are inconclusive. Data suggest risk associations vary by tumour characteristics. METHODS: We conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) to evaluate IGF-I concentrations and EOC risk by tumour characteristics (n=565 cases). Multivariable conditional logistic regression models were used to estimate associations. RESULTS: We observed no association between IGF-I and EOC overall or by tumour characteristics. CONCLUSIONS: In the largest prospective study to date was no association between IGF-I and EOC risk. Pre-diagnostic serum IGF-I concentrations may not influence EOC risk.

Hyponatraemia is a predictor of clinical outcome for malignant pleural mesothelioma.

PURPOSE: Hyponatraemia is one of the most common tumour-related electrolyte disorders. Several clinical, histological and serum factors have been found to influence prognosis, but, to date, there are no studies focusing on the prognostic role of hyponatraemia in mesothelioma. The aim of this study was to assess the prognostic role of hyponatraemia in malignant pleural mesothelioma. METHODS: We analysed 62 consecutive patients with histologically or cytologically proven advanced malignant pleural mesothelioma undergoing chemotherapy at our institution between January 2003 and September 2013. RESULTS: All patients received a first-line pemetrexed-based chemotherapy. A second-line chemotherapy was administered to 29 patients. The onset of hyponatraemia (serum sodium <135 mEq/L) during the treatment was significantly related to a worsened median overall survival (7.93 vs 13.48 months; p = 0.0069). The occurrence of hyponatraemia during first-line chemotherapy (cutoff 135 and 130 mEq/L) was significantly associated to a shorter median progression-free survival (p = 0.0214). Results were also similar in the subgroup receiving a second-line treatment. At the multivariate analysis, including haemoglobin and sodium level at the beginning of first-line chemotherapy, age, gender, smoking habit, job exposure and performance status, only hyponatraemia was found to be an independent factor (p = 0.029). Hyponatraemia was also found to be a predictive factor for both first-line chemotherapy, being related to poorer response to pemetrexed-based chemotherapy (p = 0.047) and second-line chemotherapy (p = 0.044). CONCLUSION: Our results show that hyponatraemia might be considered a negative prognostic parameter in malignant pleural mesothelioma patients. To our knowledge, this is the first study to evaluate the association of hyponatraemia with the outcome of malignant pleural mesothelioma patients.

Steroid hormone measurements from different types of assays in relation to body mass index and breast cancer risk in postmenopausal women: Reanalysis of eighteen prospective studies.

Epidemiological studies have examined breast cancer risk in relation to sex hormone concentrations measured by different methods: "extraction" immunoassays (with prior purification by organic solvent extraction, with or without column chromatography), "direct" immunoassays (no prior extraction or column chromatography), and more recently with mass spectrometry-based assays. We describe the associations of estradiol, estrone and testosterone with both body mass index and breast cancer risk in postmenopausal women according to assay method, using data from a collaborative pooled analysis of 18 prospective studies. In general, hormone concentrations were highest in studies that used direct assays and lowest in studies that used mass spectrometry-based assays. Estradiol and estrone were strongly positively associated with body mass index, regardless of the assay method; testosterone was positively associated with body mass index for direct assays, but less clearly for extraction assays, and there were few data for mass spectrometry assays. The correlations of estradiol with body mass index, estrone and testosterone were lower for direct assays than for extraction and mass spectrometry assays, suggesting that the estimates from the direct assays were less precise. For breast cancer risk, all three hormones were strongly positively associated with risk regardless of assay method (except for testosterone by mass spectrometry where there were few data), with no statistically significant differences in the trends, but differences may emerge as new data accumulate. Future epidemiological and clinical research studies should continue to use the most accurate assays that are feasible within the design characteristics of each study.

Increased rates of local complication of central venous catheters in the targeted anticancer therapy era: a 2-year retrospective analysis.

PURPOSE: Totally implantable central venous accesses (port-a-cath) are often used for chemotherapy administration or prolonged intravenous infusions in cancer patients. Local and systemic complications may occur both during and after placement of port-a-cath despite the well-established techniques for its placement and care. Out of other catheter-related local complications, thrombosis and infections represent the most common. Complications related to central venous catheter may be associated with infusion of both conventional chemotherapy and molecularly targeted therapy. Incidence and nature of complications of central venous catheter have been well established for long-term chemotherapy. However, very sparse data exists on the incidence of complications of molecularly targeted therapies administered through a central venous catheter. Hence, we decided to retrospectively analyze the local complications of a central venous catheter in patients receiving molecularly targeted therapy and conventional chemotherapy, respectively. METHODS: Over a 2-year period, 459 devices were placed in two academic Italian institutions. Patients' characteristics, catheter-related complications, and their relationship with targeted therapy administration were retrospectively assessed. RESULTS: Catheter-related complications occurred in 30 out of the 459 analyzed cancer patients (7 %). Local complications occurred in 12 (40 %) and 18 (60 %) patients receiving standard chemotherapy and biological drugs, respectively. Eighteen (72 %) out of 25 patients developing biological complications (BC) were receiving biological drugs. Infusion of a biological drug through a central venous catheter has been shown to increase the risk of central venous catheter complications (p = 0.02). No difference between the incidence of complication between anti-angiogenic and anti-epidermal growth factor receptor (EGFR) agents was observed in our study despite the statistically significant early development of port-a-cath complication in the anti-EGFR group. Treatment with a biological drug and the stage of disease, in univariate analysis, had independent effect on the duration for development of catheter-related complications. CONCLUSIONS: Molecularly targeted therapy may influence the occurrence of BCs, i.e., infection and dehiscence. Onset of BCs occurred earlier in patients receiving biological drugs (more frequently with bevacizumab than with anti-EGFR therapy) than those undergoing traditional chemotherapy. Further studies are needed to ascertain the findings of our study and to elucidate the reason for the higher incidence of catheter-related complications.

Learning from photobiology how to design molecular devices using a computer.

Biological photoreceptors and fluorescent proteins provide striking examples of how non-covalent interactions could be exploited for tuning the photochemistry and photophysics of organic chromophores. In this tutorial review we show how the construction of computer models of such natural supramolecular systems not only provides atomic-level information on the mechanisms of their function, but also principles useful for designing light-responsive components of artificial supramolecular systems. Using a few complementary case studies, the intellectual process leading to the implementation of such an engineering target is followed up to the actual construction of a working prototype of a biomimetic molecular switch.

Circulating prolactin and breast cancer risk among pre- and postmenopausal women in the EPIC cohort.

BACKGROUND: Experimental and epidemiological evidence suggests that prolactin might play a role in the etiology of breast cancer. We analyzed the relationship of prediagnostic circulating prolactin levels with the risk of breast cancer by menopausal status, use of postmenopausal hormone replacement therapy (HRT) at blood donation, and by estrogen and progesterone receptor status of the breast tumors. PATIENTS AND METHODS: Conditional logistic regression was used to analyze the data from a case-control study nested within the prospective European EPIC cohort, including 2250 invasive breast cancer and their matched control subjects. RESULTS: Statistically significant heterogeneity in the association of prolactin levels with breast cancer risk between women who were either pre- or postmenopausal at the time of blood donation was observed (Phet = 0.04). Higher serum levels of prolactin were associated with significant increase in the risk of breast cancer among postmenopausal women [odds ratio (OR)Q4-Q1 = 1.29 (95% confidence interval, CI, 1.05-1.58), Ptrend = 0.09]; however, this increase in risk seemed to be confined to women who used postmenopausal HRT at blood donation [ORQ4-Q1 = 1.45 (95% CI 1.08-1.95), Ptrend = 0.01], whereas no statistically significant association was found for the non-users of HRT [ORQ4-Q1 = 1.11 (95%CI 0.83-1.49), Ptrend = 0.80] (Phet = 0.08). Among premenopausal women, a statistically non-significant inverse association was observed [ORQ4-Q1 = 0.70 (95% CI 0.48-1.03), Ptrend = 0.16]. There was no heterogeneity in the prolactin-breast cancer association by hormone receptor status of the tumor. CONCLUSION: Our study indicates that higher circulating levels of prolactin among the postmenopausal HRT users at baseline may be associated with increased breast cancer risk.

Assessment of carbon footprint and energy performance of the extra virgin olive oil chain in Umbria, Italy.

The cradle to grave carbon footprint (CF) and energy footprint (EF) analysis of extra virgin olive oil (EVOO) produced in the Province of Perugia (Umbria, Italy) is assessed. In this study, olive orchard cultivation, EVOO extraction, bottling, packaging, storage at -18°C and distribution in the main importing countries were studied from a life cycle assessment perspective, with the main objective of identifying the processes with the largest environmental impacts. The selected functional unit was 1L of EVOO, packaged for distribution. Inventory data was gathered mainly through both direct communication using questionnaires and direct measurements. To determine the CF the ISO/TS 14067:2013 was followed while the EF was evaluated according to ISO standards 14040 and 14044. Results showed that the most impacting process is the distribution, mainly due to the choice of employing air transport. The main other hot spots identified were the olive orchard fertilization, EVOO freezing during its storage at the olive mill factory and the manufacture of glass bottles. Suggested improvement opportunities included shifts in the EVOO transportation policy, the introduction of lighter glass bottles in the bottling process, the use of cooling agent with lower global warming potential and the employment of biodiesel in the farming machineries.

Circulating concentrations of insulin-like growth factor-I, insulin-like growth factor-binding protein-3, genetic polymorphisms and mammographic density in premenopausal Mexican women: results from the ESMaestras cohort.

The insulin-like growth factor (IGF) axis plays an essential role in the development of the mammary gland. High circulating levels of IGF-I and of its major binding protein IGFBP3 have been related with increased mammographic density in Caucasian premenopausal women. Some common single nucleotide polymorphisms (SNPs) in genes of the IGF pathway have also been suggested to play a role in mammographic density. We conducted a cross-sectional study nested within the large Mexican ESMaestras cohort to investigate the relation between circulating levels of IGF-I, IGFBP-3, the IGF-I/IGFBP-3 ratio, five common SNPs in the IGF-1, IGFBP-3 and IGF-1R genes and mammographic density in 593 premenopausal Mexican women. Mean age at mammogram was 43.1 (standard deviation, SD = 3.7) years, and average body mass index (BMI) at recruitment was 28.5 kg/m(2). Mean percent mammographic density was 36.5% (SD: 17.1), with mean dense tissue area of 48.3 (SD: 33.3) cm(2) . Mean IGF-I and IGFBP-3 concentrations were 15.33 (SD: 5.52) nmol/l and 114.96 (SD: 21.34) nmol/l, respectively. No significant associations were seen between percent density and biomarker concentrations, but women with higher IGF-I and IGF-I/IGFBP-3 concentrations had lower absolute dense (p(trend) = 0.03 and 0.09, respectively) and nondense tissue areas (p(trend) < 0.001 for both parameters). However, these associations were null after adjustment by BMI. SNPs in specific genes were associated with circulating levels of growth factors, but not with mammographic density features. These results do not support the hypothesis of a strong association between circulating levels of growth hormones and mammographic density in Mexican premenopausal women.

Physical activity, sex steroid, and growth factor concentrations in pre- and post-menopausal women: a cross-sectional study within the EPIC cohort.

PURPOSE: Increased physical activity (PA) is associated with a reduced risk of several cancers. PA may reduce cancer risk by changing endogenous hormones levels, but relatively little research has focused on this topic. The purpose of this study was to elucidate the relation between PA and endogenous hormone concentrations. METHODS: A cross-sectional analysis of 798 pre- and 1,360 post-menopausal women included as controls in case-control studies on endogenous hormones (steroids, progesterone, sex-hormone-binding globulin (SHBG), and growth factors) levels, and cancer risk nested within European Prospective Investigation into Cancer and Nutrition cohort was performed. Multivariate regression analyses were performed to compare geometric mean levels of hormones and SHBG by categories of PA. RESULTS: In pre-menopausal women, active women had 19 % significantly lower concentrations of androstenedione, 14 % lower testosterone, and 20 % lower free testosterone than inactive women, while no differences were observed for estrogens, progesterone, SHBG, and growth factors. In post-menopausal women, active women had 18 % significantly lower estradiol and 20 % lower free estradiol concentrations than inactive women, while no differences were observed for the other hormones and SHBG. More vigorous forms of physical activity were associated with higher insulin-like growth factor-I concentrations. Adjustment for body mass index did not alter the associations. Overall, the percentage of variance in hormone concentrations explained by PA levels was <2 %. CONCLUSIONS: Our results support the hypothesis of an influence, although small in magnitude, of PA on sex hormone levels in blood, independent of body size.