Alleviating Breast Cancer and Cardiovascular Risks - Report Example

Alleviating Breast Cancer and Cardiovascular Risks in Obese Postmenopausal Women Author Deakin University username Name Student number Enrolled campus Table of Contents Table of Contents 2 Discussion 4 Conclusion 8 19. Levitan EB, Liu S, Stampfer MJ, et al. HbA1c measured in stored erythrocytes and mortality rate among middle-aged and older women. Diabetologia 2008;51:267-75 11 Research Translation 12 Abstract Background: Post-menopausal women have evident increases in the rates of cardiovascular diseases (CVD). CVD is a foremost reason of death in women over 49 years and is commonly detected after the onset of menopause. Approximately 500,000 women in America die every year from CVD, this equates to one death per minute (1). Study aim: to assess the efficiency of an intervention measure that encompasses reduction in fat intake to control the risk of CVD, obesity and breast cancer Method: we assessed a sample of 680 women for seven years to monitor the efficiency of the intervention measure. The diet of these women was restricted to assess the effect of reduction of fat intake. Several biomarkers of breast cancer and CVD were monitored for changes upon implementation of the intervention measures. Results: There was a significant reduction in waist circumference of participants. They also experienced significant reduction in the biomarkers for CVD and breast cancer. The control group had no significant changes in waist circumference. For the indicators of breast cancer, IGF, IL-6, CRP, TNF-α, PAI-1, VEGF, Leptin, adiponectin and resistin were reduced to near healthy levels. For CVD risk, OGTT and APOA-1 showed improvement while insulin concentration, CETP activity, free fatty acids, APOB and cortisol declined. Conclusion: our study confirms previous findings that obesity is a risk factor for breast cancer and CVD for postmenopausal women. Deductively, weight gain is a predictor of breast cancer and CVD. Discussion Post-menopausal women have increases in the rates of cardiovascular diseases CVD. Approximately 500,000 women in America die every year from CVD, this equates to one death per minute (1). Heart disease is associated with menopause because the ages of women contribute to the level of risks of heart disease. This is mainly because of the loss of estrogen. Other causes may be the changes in the walls of the blood vessels which increase the susceptibility to plaque and the formation of blood clots. According to Selvin et al (2), higher fibrinogen levels are also related to the cardiovascular disease and stroke. This study concentrated on indicators for CVD to assess the effectiveness of the intervention measure. The overall evidence from the research found that there is an increased risk of CVD with increase in body mass index (BMI). A breakdown of the biomarkers is as discussed below. Oral Glucose Tolerance Test (OGTT) is the test of insulin resistance and potential diabetic case, reactive hypoglycemia and acromegaly. The normal measure of OGTT should be below 6.1 mmol/L. fasting levels are at 6.1 and 7.0 mmol/L which is indicative of impaired glycaemia. Higher levels (above 7.0mmol/L) are indicative of a diabetic case (3). This was an important test for this study to determine the susceptibility of these women to heart diseases such as CVD. Insulin resistance is an impaired resistance to biological control of insulin levels. It may be caused by a pre-receptor, receptor or post receptor abnormality (2). Researches by Hunter & Garvey (3) have shown that insulin resistance is related to diabetes which in turn increases the risk of CVD and breast cancer. Glycated hemoglobin levels are associated with high risks of CVD and heart disease. Glycated hemoglobin is an important indicator of CVD susceptibility with Levels above 6.0 % indicating that the patient is at risk of CVD and diabetes (4, 5). Lower concentration of CETP is concomitant with and amplified risk of CVD. If the level rises the individual has 25% lower risk of heart disease. Inhibition by pharmacological means will reduce the risk of CVD as is evident in the results (6). APoA1 is the major APo in HDL particles which functions in reversal of cholesterol transport (7); it gets the excess cholesterol back to the liver. APoA1 has shown a significant increase in post intervention levels which is indicative of effectiveness of the reduction of lipid intake on achieving lower risk of CVD. APoB reflects the actual amounts of potentially atherogenic particles in the blood (8). It is responsible for the entrapment of lipoproteins on the arterial wall leading to plaque and higher risk of CVD. Even though there is evidence that development of plaque is tantamount to CVD, this aspect still need to be subjected to more research (7). By reducing the level of APoB we have consequently reduced the risk of CVD. Cushing’s syndrome which is associated with cortisol is a major risk factor for CVD. Patients with Cushing’s disease have BMI and waist circumference. The relation of Cushing’s disease to the BMI should be cautiously applied because it lacks anthropogenic data (9). Cortisol also influences the resistance to insulin. Patients treated with cortisol have higher resistance to insulin and experience elevated insulin even 5 years after the cure of Cushing’s disease (10). From the biomarkers of breast cancer, the following inferences can be made: IGF-1(ng/ml) is an important pathway for mammary gland evolution and is necessary for ductal development. However in postmenopausal women the levels drop significantly. This makes them susceptible to breast cancer as deregulated levels of IGF-1are correlated with breast cancer. Researches to reduce the action of IGF-1 are currently being done with the pretrial results indicating that the strategies will be therapeutic option for inhibiting development of both ER positive and ER negative breast cancer. The method of operation will be the blockage of effects of estrogen and progesterone on the tissues (10, 11). IL-6 (pg/ml) is an archetypal cytokine largely produced by cells in the breast tumor environment. However, IL-6 (-174G>C) is not associated with breast cancer (12). It is significantly related to the survival of breast cancer patients (13). According to Chavey (14), ERa-negative breast cancer patients have more IL-6 tumors than the Era-positive. IL-6 serum levels are higher in Era- negative patients than in those who have Era positive (15).Our results indicate concurrently higher levels in pre-intervention status while intervention resulted in significant reduction and deductively lower breast cancer risk. CRP (µg/ml) is a not directly related to any breast cancer risk. In a research by Pepys & Hirschfield (14), the highest vs. lowest multivariate hazard ratio was 0.90 with 95% confidence ratio. The same research noticed that postmenopausal women with normal levels of CRP still developed breast cancer. Our results showed little variance in post and pre intervention measures which indicates little effect of the intervention on CRP. TNF-α increases the proliferation of mammary tumors, promotes development of inflammatory responses and is critical in the pathogenesis of malignant diseases (15). The intervention caused a slight reduction in the levels of TNF-α. PAI-1(ng/ml) promotes cancer progression. Its manifestation in tumors is independent indication of poor prognosis of malignant tissue growth. There is an association between PAI-1 and breast cancer invasion (15). Our results were concurrent with Malo et al (16) and had notably little difference between the post and the pre intervention measures. VEGF (pg/ml) has been implicated in several tests for breast cancer. Higher levels are attributed to cancerous development. VEGF is linked to TNF-α in the increased permeability of endothelium (17). The high levels of VEGF in postmenopausal women are as a result of its role in age related macular degeneration. Leptin (ng/ml) is a mediator for obesity and is usually over expressed in breast cancer. It regulates endothelial cell proliferation and promotes angiogenesis. Leptin is associated with increased glucose resistance in the skeletal muscles (18). This is evidently proven by the effectiveness of reduction of waist circumference on the lower level of leptin in post intervention. Adeponectin is negatively related to insulin resistance and is inversely associated with endometrial cancer. Levitan et al (19) notes that inhibition of insulin resistance should not hinder the effect of systemic estrogen deficiency meaning that menopausal women will still have the signs of menopause. Our results are in line with the conclusions of this research as they indicate a reduction of adeponectin in women susceptible to breast cancer. Resitin is useful in providing the link between obesity and breast cancer risk (21). It has an adiposity independent role in breast cancer. Cases of breast cancer had ominously higher resistin concentration compared to the control. Conclusion CVD and breast cancer risks are high in postmenopausal women in Australia. The situation has instigated an acute need for intervention. This document reports on a research of intervention by fat intake restriction. The results indicate possible positive impact on lowering the biomarkers that indicate susceptibility to breast cancer and CVD. The restriction is intended to reduce the waist circumference and in effect obesity declines. Generally, the intervention had a good performance on its goal of reduction of CVD. As for the second aspect, the breast cancer indicators all had the expected results when the waist circumference was reduced. References 1. The Action to Control Cardiovascular Risk in Diabetes Study Group. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 2008;358:2545-59 2. Selvin E, Bolen S, Yeh HC, et al. Cardiovascular outcomes in trials of oral diabetes medications: a systematic review. Arch Intern Med 2008;168:2070-80 3. Dr Jane Patmore (2009). "Oral Glucose Tolerance Tests: Protocol and Guidance". Hull and East Riding Diabetes Network, Hull NHS teaching hospitals trust. Retrieved 2012-06-20. 4. Davila JA, Morgan RO, Shaib Y, et al. Diabetes increases the risk of hepatocellular carcinoma in the United States: a population based case control study. Gut 2005;54:533-539 5. Pilz S, Scharnagl H, Tiran B, Seelhorst U, Wellnitz B, Boehm BO, Schaefer JR, März W (2006) Free fatty acids are independently associated with all-cause and cardiovascular mortality in subjects with coronary artery disease. J Clin Endocrinol Metab 91:2542–2547 6. Faergeman O. Apolipoproteins and guidelines for prevention of cardiovascular disease. J Intern Med 2006; 259: 434–436 7. Litovkin KV, Domenyuk VP, Bubnov VV, Zaporozhan VN (2007) Interleukin-6 -174G/C polymorphism in breast cancer and uterine leiomyoma patients: a populationbased case control study. Exp Oncol 29:295-298. 8. Lind L. Vasodilation in resistance arteries is related to the apolipoprotein B/A-I ratio in the elderly. The Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Atherosclerosis 2006; March 14: Epub ahead of print. 9. Erez N, Truitt M, Olson P, Arron ST, Hanahan D (2010) Cancer-Associated Fibroblasts Are Activated in Incipient Neoplasia to Orchestrate Tumor-Promoting Inflammation in an NF-kappaB-Dependent Manner. Cancer Cell 17:135-147. 10. Ruan W, Monaco ME, Kleinberg DL. Progesterone stimulates mammary gland ductal morphogenesis by synergizing with and enhancing insulin-like growth factor-1 action. Endocrinology 2005; 146: 1170–1178. 11. Ruan W, Fahlbusch F, Clemmons DR et al. SOM230 inhibits IGF-I action in mammary gland development by pituitary independent mechanism: mediated through somatostatin subtype receptor 3? Mol Endocrinol 2006; 20: 426–436. 12. Yu KD, Di GH, Fan L, Chen AX, Yang C, Shao ZM (2009b) Lack of an association between a functional polymorphism in the interleukin-6 gene promoter and breast cancer risk: a meta-analysis involving 25,703 subjects. Breast Cancer Res Treat 122:483-488 13. Gonzalez-Zuloeta Ladd AM, Arias Vasquez A, Witteman J, Uitterlinden AG, Coebergh JW, Hofman A, et al. (2006) Interleukin 6 G-174 C polymorphism and breast cancer risk. Eur J Epidemiol 21:373-376. 14. Chavey C, Bibeau F, Gourgou-Bourgade S, Burlinchon S, Boissiere F, Laune D, et al. (2007) Oestrogen receptor negative breast cancers exhibit high cytokine content. Breast Cancer Res 9:R15. 15. Kim HJ, Litzenburger BC, Cui X et al. Constitutively active type I insulin-likegrowth factor receptor causes transformation and xenograft growth of immortalized mammary epithelial cells and is accompanied by an epithelial-tomesenchymal transition mediated by NF-kappaB and snail. Mol Cell Biol 2007; 27: 3165–3175. 16. Malo M, Charriere-Bertrand C, Chettaoui C, Fabre-Guillevin E, Maquerlot F, Lackmy A, Vallee B, Delaplace F, Barlovatz-Meimon G: [The PAI-1 swing: microenvironment and cancer cell migration]. C R Biol 2006, 329:919-927 17. Xu J, Zhou JY, Wu GS: Tumor necrosis factor-related apoptosis-inducing ligand is required for tumor necrosis factor alphamediated sensitization of human breast cancer cells to chemotherapy. Cancer Res 2006, 66:10092 18. Stanley WC, Recchia FA, Lopaschuk GD (2005) Myocardial substrate metabolism in the normal and failing heart. Physiology Review 85:1093–1129. 19. Levitan EB, Liu S, Stampfer MJ, et al. HbA1c measured in stored erythrocytes and mortality rate among middle-aged and older women. Diabetologia 2008;51:267-75 20. Ron Walls MD; John J. Ratey MD; Robert I. Simon MD (2009). Rosen's Emergency Medicine: Expert Consult Premium Edition - Enhanced Online Features and Print (Rosen's Emergency Medicine: Concepts & Clinical Practice (2v.)). St. Louis: Mosby. Research Translation Obesity in postmenopausal women is a leading factor in development of health issues such as cardiovascular diseases and breast cancer. This is attributed to the decline in efficiency of inhibitors to malignant growth of cells and the increase in development of plaque in the arterial walls. Plaque leads to hypertension while failure of malignant cell growth inhibition leads to cancers. Postmenopausal women with obesity have generally higher fat and lipid intake which unless controlled leads to their susceptibility to CVD and breast cancer. This research restricted and reduced the intake of fat and checked the biomarkers which are used to detect the development of CVD and breast cancer. The results for CVD indicate that with reduced waist circumference and in turn lower obesity, postmenopausal women have a significant increase in OGTT and APoA1 levels. This shows that with lesser body mass index the women can inhibit diabetes causing risk factors (OGTT) and reverse cholesterol accumulation in the vascular system (APoA1). By lowering the risk factors such as insulin concentration, CETP activity, APoB, Free fatty acids and cortisol, the risk of development of CVD is reduced. This occurs because the cumulative effect of chemicals on increasing susceptibility to CVD is reduced. Glycated hemoglobin remains unchanged as it is not directly related to development of CVD. Intervention measures therefore did not affect any change on its levels. In the tests for breast cancer, the biomarkers were tested for over expression which would be indication of breast cancer. The intervention measures should have a reduction of the over expression as was shown in the results. Biomarkers for breast cancer showed efficiency of the intervention measure as there was a significant difference between the pre intervention and post intervention. Adeponectin and PAI-1 are notably not directly related to development of cancer. Their levels are not dependent on the obesity or BMI. The intervention measures therefore did not have much effect on their level. Adeponectin is in fact inversely related to breast cancer development. The other biomarkers were contrary to the two mentioned above. There was much difference in the levels of IGF-1, IL-6,CRP, TNF-α, VEGF, Leptin and, resistin( p≤0.05 for waist circumference ≥90cm). The biomarkers for the control group remained unchanged. Read More