Tamoxifen and Flaxseed Alter Angiogenesis Regulators in Normal Human Breast Tissue In Vivo

The incidence of breast cancer is increasing in the Western world and there is an urgent need for studies of the mechanisms of sex steroids in order to develop novel preventive strategies. Diet modifications may be among the means for breast cancer prevention. Angiogenesis, key in tumor progression, is regulated by the balance between pro- and anti-angiogenic factors, which are controlled in the extracellular space. Sampling of these molecules at their bioactive compartment is therefore needed. The aims of this study were to explore if tamoxifen, one of the most used anti-estrogen treatments for breast cancer affected some of the most important endogenous angiogenesis regulators, vascular endothelial growth factor (VEGF), angiogenin, and endostatin in normal breast tissue in vivo and if a diet supplementation with flaxseed had similar effects as tamoxifen in the breast. Microdialysis was used for in situ sampling of extracellular proteins in normal breast tissue of women before and after six weeks of tamoxifen treatment or before and after addition of 25 g/day of ground flaxseed to the diet or in control women. We show significant correlations between estradiol and levels of VEGF, angiogenin, and endostatin in vivo, which was verified in ex vivo breast tissue culture. Moreover, tamoxifen decreased the levels of VEGF and angiogenin in the breast whereas endostatin increased significantly. Flaxseed did not alter VEGF or angiogenin levels but similar to tamoxifen the levels of endostatin increased significantly. We conclude that one of the mechanisms of tamoxifen in normal breast tissue include tipping of the angiogenic balance into an anti-angiogenic state and that flaxseed has limited effects on the pro-angiogenic factors whereas the anti-angiogenic endostatin may be modified by diet. Further studies of diet modifications for breast cancer prevention are warranted

The burden of breast, cervical, and colon and rectum cancer in the Balkan countries, 1990–2019 and forecast to 2030.

Background Despite effective prevention and control strategies, in countries of the Balkan region, cancers are the second leading cause of mortality, closely following circulatory system diseases. Objective To describe trends in the burden of breast, cervical, and colon and rectum cancer in the Balkan region and per country between 1990 and 2019, including a forecast to 2030. Methods We described the 2019 Global Burden of Disease (GBD) estimates for breast, cervical, and colon and rectum cancers in eleven Balkan countries over the period 1990–2019, including incidence, years lived with disability (YLD), years of life lost (YLL), and disability-adjusted life years (DALYs) rates per 100,000 population and accompanied 95% uncertainty interval. With the Autoregressive Integrated Moving Average, we forecasted these rates per country up to 2030. Results In the Balkan region, the highest incidence and DALYs rates in the study period were for colon and rectum, and breast cancers. Over the study period, the DALYs rates for breast cancer per 100,000 population were the highest in Serbia (reaching 670.84 in 2019) but the lowest in Albania (reaching 271.24 in 2019). In 2019, the highest incidence of breast cancer (85 /100,000) and highest YLD rate (64 /100,000) were observed in Greece. Romania had the highest incidence rates, YLD rates, DALY rates, and YLL rates of cervical cancer, with respective 20.59%, 23.39% 4.00%, and 3.47% increases for the 1990/2019 period, and the highest forecasted burden for cervical cancer in 2030. The highest incidence rates, YLD rates and DALY rates of colon and rectum cancers were continuously recorded in Croatia (an increase of 130.75%, 48.23%, and 63.28%, respectively), while the highest YLL rates were in Bulgaria (an increase of 63.85%). The YLL rates due to colon and rectum cancers are forecasted to progress by 2030 in all Balkan countries. Conclusion As most of the DALYs burden for breast, cervical, and colon and rectum cancer is due to premature mortality, the numerous country-specific barriers to cancer early detection and quality and care continuum should be a public priority of multi-stakeholder collaboration in the Balkan region

Variation in fasting and non-fasting serum enterolactone concentrations in women of the Malmo Diet and Cancer cohort

Objectives:The aim of this study was to examine the variation of enterolactone from fasting and non-fasting blood of middle-aged healthy women eating a normal diet to determine the usefulness of a single sample in epidemiological studies.Subjects and methods:Twenty-six women born between 1940 and 1950 were recruited within the Malmo Diet and Cancer cohort. Three non-fasting and two overnight fasting samples were collected from each individual during a 5-week period. Twenty-one participated in all measurements. Enterolactone concentrations were analyzed by time-resolved fluoroimmunoassay.Results:The within-subject and between-subject variations (coefficient of variations, CV) were estimated to 59 and 89% respectively for fasting samples and 71 and 67% for non-fasting samples. The intraclass correlation coefficients (ICC) were estimated to 0.66 (95% confidence interval (CI) 0.35-0.84) for fasting and 0.48 (95% CI, 0.22-0.72) for non-fasting samples.Conclusions:Although the estimated ICC for blood samples was moderate, it indicates that enterolactone levels of both fasting and non-fasting blood samples should be useful in future projects within the Malmo Diet and Cancer cohort.European Journal of Clinical Nutrition advance online publication, 30 May 2007; doi:10.1038/sj.ejcn.1602811

Estimated enterolignans, lignan-rich foods, and fibre in relation to survival after postmenopausal breast cancer

BACKGROUND: Lignans – oestrogenic substances present in various foods – are associated with postmenopausal breast cancer risk, but not much is known regarding their effects on survival. METHODS: In a follow-up study of 2653 postmenopausal breast cancer patients diagnosed between 2001 and 2005, vital status and causes of death were verified through end of 2009. Hazard ratios (HRs) and 95% confidence intervals (CIs) for estimated enterolignans, lignan-rich foods, and dietary fibre in relation to overall survival (OS) and breast cancer-specific survival (BCSS) were assessed using Cox proportional hazards models stratified by age at diagnosis and adjusted for prognostic/confounding factors. RESULTS: Median follow-up time was 6.4 years, and 321 women died, 235 with breast cancer. High estimated enterolactone and enterodiol levels were associated with significantly lower overall mortality (highest quintile, HR=0.60, 95% CI=0.40–0.89, P(Trend)=0.02 and HR=0.63, 95% CI=0.42–0.95, P(Trend)=0.02, respectively). Fibre intake was also associated with a significantly lower overall mortality. Differentiated by median fibre intake, associations with estimated enterolignans were still evident at low but not high fibre intake. There was no effect modification by oestrogen receptor status and menopausal hormone therapy. CONCLUSION: Postmenopausal breast cancer patients with high estimated enterolignans may have a better survival

Investigation into the cancer protective effect of flaxseed in Tg.NK (MMTV/c-neu) mice, a murine mammary tumor model

The aim of the present study was to investigate whether low flaxseed doses relevant to human dietary exposure can prevent mammary tumors in transgenic Tg.NK mice, a model of breast cancer. Animals were exposed to flaxseed through the diet at human relevant levels. Tumor-related parameters and tumor development were evaluated. Hepatic cytochrome P450 and glutathione S-transferase activities were significantly reduced in animals receiving low flaxseed doses. An incidence of palpable tumors before sacrifice, a number of tumors per mouse, and a number of large tumors (>6 mm diameter) at necropsy were statistically significantly lower in the high flaxseed group compared to controls, suggesting a beneficial effect on tumor progression of small dietary doses of flaxseed. However, the number of tumor-bearing mice and multiplicity of tumors at necropsy were not statistically significantly lower compared to the controls. Thus, the effect of small dietary doses of flaxseed on mammary tumor development in Tg.NK mice remains to be established. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12263-011-0214-1) contains supplementary material, which is available to authorized users