Fatal myocardial infarction in the Scottish adjuvant tamoxifen trial. The Scottish Breast Cancer Committee.

McDonald, C.; Stewart, Helen

doi:10.1136/bmj.303.6800.435

Cited by 340 publications

(107 citation statements)

References 18 publications

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“…A haemodilutory action may contribute to the cardioprotective effects of tamoxifen in postmenopausal women. Studies in women with breast cancer suggest that tamoxifen may substantially reduce the risk of dying from cardiovascular disease [1,6,7]. This effect is likely to be, in part, attributable to favourable effects on serum lipids and haemostatic factors [3,5,13].…”

Section: Discussionmentioning

confidence: 99%

The anti‐oestrogen tamoxifen produces haemodilution in normal postmenopausal women

Grey

Evans

Kyle

et al. 1997

Journal of Internal Medicine

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Abstract. Grey AB, Evans MC, Kyle C, Reid, IR (University of Auckland, Auckland, New Zealand). The anti-oestrogen tamoxifen produces haemodilution in normal postmenopausal women. J Intern Med 1997; 242: 383-8. Objectives.To report the effects of the anti-oestrogen tamoxifen on biochemical and haematological parameters. Design. Randomized, double-blind comparison of tamoxifen 20 mg per day and placebo, over two years. Setting. A university hospital. Subjects. Forty-six healthy late-postmenopausal women (mean, SD time since menopause; 11, seven years). Main outcome measures. Blood specimens were drawn in the fasting state at baseline, six months and two years for measurement of haemoglobin, haematocrit, erythrocyte mean cell volume, mean erythrocyte haemoglobin, leucocyte count, platelet count, urea, electrolytes, creatinine and albumin.Results. There was a significant decline in the haemoglobin concentration in the tamoxifen group (Ϫ4.4, 1.2 g/L; mean, SE) and its levels were lower in this group than in those receiving placebo (P ϭ 0.004). Similarly, haematocrit, erythrocyte count and total leucocyte count were lower in those on placebo (P ϭ 0.002, P ϭ 0.01 and P ϭ 0.01, respectively) and platelet count showed a similar trend (P ϭ 0.08). In the tamoxifen group, the level of serum albumin fell significantly (Ϫ2.2, 0.4 g/L) and was lower throughout the study than that in the placebo group (P ϭ 0.006). That of serum urea tended to fall (Ϫ0.4, 0.2 mmol L) but the between-groups comparison was not significant (P ϭ 0.18). Conclusions. These data suggest that tamoxifen exerts a haemodilutory effect in normal postmenopausal women. Since a similar effect has been reported in response to postmenopausal oestrogen therapy, it is likely that the observed changes represent another oestrogenic effect of tamoxifen in postmenopausal women. Haemodilution may contribute to the reduced incidence of cardiovascular disease reported in tamoxifen-treated women, and, therefore, its assessment in the new oestrogen agonists/antagonists being developed for cardiovascular disease prevention may be important.

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Section: Discussionmentioning

confidence: 99%

The anti‐oestrogen tamoxifen produces haemodilution in normal postmenopausal women

Grey

Evans

Kyle

et al. 1997

Journal of Internal Medicine

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“…The pattern of response bore a greater similarity to Tamoxifen (the anti-oestrogen drug successfully employed in breast-cancer treatment) than to HRT. This overall similarity between Raloxifene and Tamoxifen may be important, since the changes in risk factors induced by Tamoxifen may be responsible for the observed decrease in CHD mortality in women receiving Tamoxifen (McDonald & Stewart, 1991).…”

Section: Hormone-replacement Therapymentioning

confidence: 89%

Phyto-oestrogens: A potential role in the prevention of CHD?

Cassidy

Griffin

1999

Proc. Nutr. Soc.

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CHD is a major cause of morbidity and mortality in women. The incidence of CHD in premenopausal women is low but increases substantially after the menopause, and this difference suggests that endogenous oestrogens are cardioprotective. Observational prospective studies have consistently shown that exogenous oestrogens also lower CHD risk. The biological mechanisms by which endogenous and exogenous oestrogens exert their protective effect are multifactorial, affecting lipids, carbohydrate metabolism, body fat distribution and blood pressure. The prevention of CHD with oestrogen therapy i s therefore aimed both at correction of the traditional risk factors and at direct control of vessel structure and function. The wide international variation in rates of CHD together with the lower mortality in sub-groups of the population suggests that aconsiderable proportion of CHD may be prevented by dietary modification. Since phytooestrogens are structually similar to oestrogen, they have the potential to mimic its effects in vivo. The hypocholesterolaemic effects of soyabean protein (rich in phyto-oestrogen precursors) are well established, but the underlying mechanism and atherogenic potential of these changes are unknown. One isoflavone, genistein, has been shown in vitro to exert effects which may slow the development of atherosclerotic disease. However, further studies are required to determine the dose-related changes induced by phyto-oestrogens on serum lipoproteins, haemostasis and vascular function. Phyto-oestrogens: Oestrogens: Lignans: Soyabean: CHDAt any given age death rates in the UK for CHD in women are equivalent to the rates observed in men 10 years younger. Nevertheless, CHD is still a major cause of morbidity and mortality in women, and accounts for 23 % of female mortality (Williams, 1997). Women appear to be protected from CHD in the premenopausal years and this pre-v. post-menopausal difference in CHD risk suggests a protective role for endogenous oestrogens. Evidence for the influence of oestrogens on CHD risk factors is derived from two principal sources: (1) from changes in lipoprotein metabolism and other risk variables on progression to themenopause; (2) from the impact of oestrogen administration. Since lifelong use of exogenous oestrogen is required for cardioprotection (Grodstein et al. 1996), the long-term risk-benefit balance is crucial. Cross-cultural trends in the incidence rate of CHD, and the lower mortality observed in vegetarians (Key etal. 1996), suggest that a considerable proportion of CHD may be preventable through diet. Large-scale epidemiological studies have highlighted the potential benefits of increased fruit and vegetable intake, specifically in relation to antioxidant nutrients and phenolic flavonoids (Hertog et al. 1993; Gaziano el al. 1995;Pandey et al. 1995). Plant foods also contain nonsteroidal phyto-oestrogens, and these weakly oestrogenic compounds may harbour considerable potential to act as oestrogen agonists in vivo and may play a vital role in the prevention of CH...

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“…The effects of tamoxifen therapy on HDL cholesterol have varied across previous studies and have mostly been marginal. Retrospective studies have suggested a reduction of cardiac morbidity among tamoxifen users (McDonald and Stewart, 1991;Rutqvist and Mattsson, 1993), which has been related to the cholesterol-lowering effect of antioestrogens. However, a large double-blind, randomised, placebo-controlled NSABP Breast Cancer Prevention Trial (BCPT) reported that prophylactic tamoxifen did not influence cardiovascular risk in 13 388 women (Fisher et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

“…Uniformly, the levels of total cholesterol and LDL cholesterol decrease significantly during tamoxifen treatment, but the effects on HDL cholesterol and triglycerides have varied (Love et al, 1990;Grey et al, 1995;Saarto et al, 1996b;Decensi et al, 1998). Two retrospective, randomised trials suggested that tamoxifen might have a cardioprotective effect in postmenopausal women (McDonald and Stewart, 1991;Rutqvist and Mattsson, 1993). However, a large placebo-controlled randomised study failed to show any effects of tamoxifen on cardiovascular risk (Fisher et al, 1998).…”

mentioning

confidence: 99%

Tamoxifen treatment reverses the adverse effects of chemotherapy-induced ovarian failure on serum lipids

et al. 2004

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In all, 146 premenopausal women with early stage breast cancer were treated with adjuvant chemotherapy. In addition, 5-year tamoxifen treatment was started after chemotherapy to those 112 patients with hormone-receptor-positive tumours while those with hormone-receptor-negative tumours received no further therapy. The serum lipid levels were followed in both groups. The levels of serum total and low-density lipoprotein (LDL) cholesterol increased significantly after chemotherapy only in patients who developed ovarian dysfunction. Total cholesterol increased þ 9.5% and LDL cholesterol þ 16.6% in patients who developed amenorrhoea (Po0.00001 and 0.00001, respectively). The cholesterol levels did not change in patients who preserved regular menstruation after chemotherapy. After 6 months of tamoxifen therapy, the total cholesterol decreased À9.7% and the LDL cholesterol À16.7% from levels after the chemotherapy, while the cholesterol concentrations remained at increased levels in the control group (P ¼ 0.001 and Po0.0001, respectively). The high-density lipoprotein cholesterol levels did not change significantly in either tamoxifen or control group. The effects of tamoxifen treatment on serum lipids after chemotherapy have not been studied before. Our current study suggests that adjuvant tamoxifen therapy reverses the adverse effects of chemotherapy-induced ovarian failure on total and LDL cholesterol and even lowers their serum levels below the baseline.

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Fatal myocardial infarction in the Scottish adjuvant tamoxifen trial. The Scottish Breast Cancer Committee.

Cited by 340 publications

References 18 publications

The anti‐oestrogen tamoxifen produces haemodilution in normal postmenopausal women

The anti‐oestrogen tamoxifen produces haemodilution in normal postmenopausal women

Phyto-oestrogens: A potential role in the prevention of CHD?

Tamoxifen treatment reverses the adverse effects of chemotherapy-induced ovarian failure on serum lipids

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