Effect of tamoxifen and transdermal hormone replacement therapy on cardiovascular risk factors in a prevention trial

DeCensi, Andrea; Robertson, Chris; Rotmensz, Nicole; Severi, Gianluca; Maisonneuve, Patrick; Sacchini, Virgilio; Boyle, P; Costa, Alberto; Veronesi, Umberto

doi:10.1038/bjc.1998.542

Cited by 32 publications

(16 citation statements)

References 44 publications

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“…Our findings confirm and strengthen the interpretation of prior reports of lower fibrinogen and cholesterol with tamoxifen [2][3][4][5][6]32 and its analogue droloxifene 33 and provide new information concerning C-reactive protein. When the population of women eligible for tamoxifen for the prevention of breast cancer is considered, relevant features of the present study compared with prior studies are as follows: exclusion of women with cancer, 2,32 prohibition of postmenopausal hormone use concurrent with study medication, 4,6 sufficient power, 4,34 and a double-blind control group.…”

Section: Discussionsupporting

confidence: 90%

“…We had insufficient blood volume to determine the effects of tamoxifen on lipid subfractions, but other studies have provided information in this regard. [2][3][4]6 For practical purposes, phlebotomy for the present study was not always performed in the morning with the subjects in a fasting state. Even though we adjusted for this, diurnal variation was not controlled and may have influenced our results for fragment 1-2, 39 biasing findings toward the null hypothesis.…”

Section: Discussionmentioning

confidence: 99%

“…1 Similar to postmenopausal hormone therapy, tamoxifen was predicted to reduce cardiovascular risk on the basis of its lipid-lowering properties. [2][3][4][5][6] Indeed, 3 trials of breast cancer patients have reported 15% to 60% reductions in cardiac death in women treated with tamoxifen. [7][8][9] In the P-1 trial, myocardial infarction rates comparing tamoxifen and placebo did not differ.…”

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confidence: 99%

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Tamoxifen and Cardiac Risk Factors in Healthy Women: Suggestion of an Anti-Inflammatory Effect

Cushman¹,

Costantino²,

Tracy³

et al. 2001

Obstetrical and Gynecological Survey

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Abstract-Tamoxifen reduces the incidence of breast cancer in women at risk for that disease. Because heart disease is the leading cause of death in women and because tamoxifen is also associated with venous thrombosis, an improved understanding of the association of tamoxifen with cardiovascular disease risk factors is required. In 111 healthy women at a single center, who were participating in a randomized double-blind breast cancer prevention trial, the 6-month effects of oral tamoxifen (20 mg/d) compared with placebo on factors related to inflammation, hemostasis, and lipids were studied. Tamoxifen was associated with reductions of 26% in median C-reactive protein, 22% in median fibrinogen, and 9% in cholesterol (all PϽ0.01 compared with placebo). There were no differences in treatment effects on factor VII coagulant activity, fragment 1-2, and triglycerides. In secondary analyses, the effect of tamoxifen on C-reactive protein was larger in postmenopausal women and in women with higher waist-to-hip ratios. The effect on fibrinogen was larger in women with higher baseline cholesterol. Tamoxifen demonstrated effects on inflammatory markers that were consistent with reduced cardiovascular risk. These findings are in contrast to recent reports of increased C-reactive protein associated with postmenopausal estrogen.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Tamoxifen and Cardiac Risk Factors in Healthy Women: Suggestion of an Anti-Inflammatory Effect

Cushman¹,

Costantino²,

Tracy³

et al. 2001

Obstetrical and Gynecological Survey

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“…31). In addition, results from the Italian Chemoprevention Group trial showed that after 12 months of tamoxifen (n = 1,117), there was no effect on platelet count (32). The phase II trial (study 223) of neoadjuvant anastrozole alone or with gefitinib (34) acquired information on platelet counts at baseline and after 4 months of anastrozole alone.…”

Section: Discussionmentioning

confidence: 99%

The Effects of Neoadjuvant Anastrozole and Tamoxifen on Circulating Vascular Endothelial Growth Factor and Soluble Vascular Endothelial Growth Factor Receptor 1 in Breast Cancer

Banerjee

Pancholi

A’Hern

et al. 2008

Clinical Cancer Research

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Purpose: Vascular endothelial growth factor (VEGF) is a key angiogenic factor mediating neovascularization. Soluble VEGF receptor 1 (sVEGFR-1) is an intrinsic negative counterpart of VEGF signaling and the ratio of sVEGFR-1 to VEGF has been shown to be a prognostic factor. Estrogen-bound estrogen receptor enhancesVEGF expression, providing a common link between these signaling pathways that may be targeted by endocrine therapy.We investigated the effects of anastrozole and tamoxifen over time on serum VEGF and sVEGFR-1. Experimental Design: The Immediate Preoperative Anastrozole, Tamoxifen, or Combined with Tamoxifen (IMPACT) trial compared the preoperative use of anastrozole with tamoxifen in postmenopausal women with estrogen receptor^positive primary operable breast cancer over 12 weeks. Circulating VEGF and sVEGFR-1were measured by ELISA in 106 patients treated with anastrozole or tamoxifen alone at baseline and after 2 and 12 weeks of treatment. Results: The increase in serum VEGF from baseline to 12 weeks was significantly different between anastrozole and tamoxifen (anastrozole versus tamoxifen, 6% versus 38%; P = 0.047). There was a significant increase in sVEGFR-1levels after 12 weeks of anastrozole (P = 0.037).The sVEGFR-1/VEGF ratio significantly decreased in the tamoxifen arm (P = 0.013) and the change in sVEGFR-1/VEGF ratio from baseline to 12 weeks was significantly different between anastrozole and tamoxifen (anastrozole versus tamoxifen, 24% increase versus 34% decrease; P = 0.013). Conclusions: Treatment with anastrozole and tamoxifen resulted in differential effects on serum angiogenic markers.This may be related to the relative effectiveness of the treatments.These data provide further support for cross talk between estrogen receptor and VEGF.

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“…The effects of tamoxifen on serum lipids have been extensively studied. 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).…”

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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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Effect of tamoxifen and transdermal hormone replacement therapy on cardiovascular risk factors in a prevention trial

Cited by 32 publications

References 44 publications

Tamoxifen and Cardiac Risk Factors in Healthy Women: Suggestion of an Anti-Inflammatory Effect

Tamoxifen and Cardiac Risk Factors in Healthy Women: Suggestion of an Anti-Inflammatory Effect

The Effects of Neoadjuvant Anastrozole and Tamoxifen on Circulating Vascular Endothelial Growth Factor and Soluble Vascular Endothelial Growth Factor Receptor 1 in Breast Cancer

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

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