Effects of Tamoxifen on Cardiovascular Risk Factors in Postmenopausal Women After 5 Years of Treatment

Love, Richard R.; Wiebe, Donald A.; Feyzi, Jan; Newcomb, Polly A.; Chappell, Richard J.

doi:10.1093/jnci/86.20.1534

Cited by 260 publications

(117 citation statements)

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“…Despite evidence that tamoxifen lowers serum lipid levels in postmenopausal women with breast cancer (Love et al, 1994;Thangaraju et al, 1994) and is associated with a pattern of inflammatory markers suggesting reduced cardiovascular disease risk (Cushman et al, 2001), tamoxifen trials have not demonstrated a consistent, statistically significant reduction in morbidity or mortality due to MI. McDonald et al (1995) reported a hazard ratio of 1.92 (95% CI 0.99-3.73) for MI in women randomised to the control arm relative to those randomised to the tamoxifen arm.…”

Section: Discussionmentioning

confidence: 99%

“…Tamoxifen appears to lower serum lipid levels in postmenopausal women with breast cancer (Love et al, 1994;Thangaraju et al, 1994) and has been associated with a pattern of inflammatory markers suggesting reduced cardiovascular disease risk (Cushman et al, 2001). In treatment trials, tamoxifen has been associated with reduced cardiovascular disease events, but these results have been of borderline or no statistical significance when considering only myocardial infarction (MI) (Rutqvist and Mattsson, 1993;McDonald et al, 1995).…”

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Myocardial infarction risk and tamoxifen therapy for breast cancer

2005

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Tamoxifen prevents recurrence after breast cancer and breast cancer among high-risk women, and may prevent myocardial infarction (MI). To assess the impact of tamoxifen on MI risk, we conducted a case -control study of first MI after breast cancer nested among women diagnosed with breast cancer, while enrolled in a health maintenance organisation from 1980 to 2000. We obtained information on breast cancer treatment and MI risk factors through medical record reviews and interviews. Data were analysed using conditional logistic regression. Of 11 045 women with breast cancer, 134 met MI criteria and were matched to two MI-free control subjects on year of birth and breast cancer diagnosis. After adjusting for smoking, hypertension and diabetes, tamoxifen was unassociated with MI (odds ratio (OR) ¼ 1.2, 95% confidence interval (CI) ¼ 0.7 -1.9). Duration, cumulative dose and recency of use were not associated with MI. Radiation therapy was associated with MI (OR ¼ 2.0, 95% CI ¼ 1.1 -3.5), an association that varied slightly but not statistically significantly by tamoxifen use (radiation with tamoxifen, OR ¼ 2.0, 95% CI ¼ 0.9 -4.4; radiation without tamoxifen, OR ¼ 2.9, 95% CI ¼ 1.2 -7.5). Tamoxifen treatment for breast cancer does not appear to increase or decrease MI risk, although radiation therapy appears to increase MI risk.

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Section: Discussionmentioning

confidence: 99%

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Myocardial infarction risk and tamoxifen therapy for breast cancer

2005

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“…1993, Love et al . 1994 a , b ). In addition, tamoxifen and its active metabolite 4-hydroxytamoxifen have marked estrogenic activity in the uterus of ovariectomized rats or mice and are associated with an increased risk of endometrial cancer in the clinic (Martin & Middleton 1978, Davies et al .…”

Section: Serms Vs Serds: Two Separate Classes Of Antiestrogens?mentioning

confidence: 99%

Antiestrogens: structure-activity relationships and use in breast cancer treatment

Traboulsi

Ezzy

Gleason

et al. 2017

Journal of Molecular Endocrinology

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About 70% of breast tumors express estrogen receptor alpha (ERα), which mediates the proliferative effects of estrogens on breast epithelial cells, and are candidates for treatment with antiestrogens, steroidal or non-steroidal molecules designed to compete with estrogens and antagonize ERs. The variable patterns of activity of antiestrogens (AEs) in estrogen target tissues and the lack of systematic cross-resistance between different types of molecules have provided evidence for different mechanisms of action. AEs are typically classified as selective estrogen receptor modulators (SERMs), which display tissue-specific partial agonist activity (e.g. tamoxifen and raloxifene), or as pure AEs (e.g. fulvestrant), which enhance ERα post-translational modification by ubiquitin-like molecules and accelerate its proteasomal degradation. Characterization of second- and third-generation AEs, however, suggests the induction of diverse ERα structural conformations, resulting in variable degrees of receptor downregulation and different patterns of systemic properties in animal models and in the clinic.

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“…Although part of the protective cardiovascular effect of tamoxifen may be associated to the modulation of cholesterol, lipoproteins and fibrinogen levels (Love et al, 1994), a recent uncontrolled study showed that tamoxifen, given at a dose of 30 mg day-', lowered total plasma homocysteine (tHcy) levels in patients with advanced breast cancer (Anker et al, 1995). Homocysteine is a sulphydryl amino acid derived from the metabolic conversion of methionine, which proved to be an independent risk factor for premature occlusive disease of the coronary, cerebral and peripheral arteries in case-control and prospective studies (Boushey et al, 1995;McCully, 1996;Graham et al, 1997).…”

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Tamoxifen reduces plasma homocysteine levels in healthy women

Cattaneo

Baglietto²,

Zighetti³

et al. 1998

Br J Cancer

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Summary Treatment with tamoxifen is associated with reduced incidence of myocardial infarction. As plasma homocysteine is an independent risk factor for cardiovascular disease, we studied the effects of tamoxifen on plasma homocysteine in 66 healthy women participating in the Italian prevention trial of breast cancer who were randomized in a double-blind manner to tamoxifen 20 mg day-' or placebo for 5 years. They were aged between 35 and 70 years, had undergone previous hysterectomy for non-malignant conditions and had no cont(aindications to the use of tamoxifen. Plasma levels of total homocysteine (tHcy) were measured at randomization and after 2 and 6 months. The mean ± s.d. plasma levels of tHcy were 7.59 + 1.71 lmol 1-', 7.25 ± 1.61 and 7.09 + 1.33 in the tamoxifen group and 8.07 ± 2.06, 7.93 ± 1.77 and 8.12 + 2.04 in the placebo group at 0, 2 and 6 months (P= 0.008 for the between-group difference over time). The higher the baseline tHcy level, the greater was the lowering effect of tamoxifen. No statistically significant effect of age, body mass index or smoking habit on baseline tHcy levels and its variation over time was found. In conclusion, tamoxifen (20 mg day-' for 6 months) decreased plasma tHcy levels in healthy women. This effect may contribute to its protective effect on myocardial infarction.

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Effects of Tamoxifen on Cardiovascular Risk Factors in Postmenopausal Women After 5 Years of Treatment

Cited by 260 publications

References 0 publications

Myocardial infarction risk and tamoxifen therapy for breast cancer

Myocardial infarction risk and tamoxifen therapy for breast cancer

Antiestrogens: structure-activity relationships and use in breast cancer treatment

Tamoxifen reduces plasma homocysteine levels in healthy women

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