Cardiac and vascular morbidity in women receiving adjuvant tamoxifen for breast cancer in a randomised trial

McDonald, C.; Alexander, Freda E.; Whyte, Bruce; Forrest, A. P. M.; Stewart, H.J.

doi:10.1136/bmj.311.7011.977

Cited by 267 publications

(133 citation statements)

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“…As hyperhomocysteinaemia is an independent graded risk factor for atherosclerotic vascular disease (Boushey et al, 1995;McCully, 1996;Graham et al, 1997;Nyg'ard et al, 1997), the reduction in tHcy concentration may partly explain the preventive effect of tamoxifen on cardiovascular morbidity observed in trials of adjuvant therapy (Rutqvuist et al, 1993;McDonald et al, 1995). It has been calculated that a decrease of 2 ,tmol 1-' in plasma tHcy concentration of women living in the US would prevent between 6000 and 11 500 coronary deaths annually (Boushey et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

“…In light of the partial agonistic activity, which reflects the complex regulation of oestrogen signalling in the body (Pennisi, 1996), tamoxifen treatment has also been associated with a reduction in coronary heart disease (Rutqvist et al, 1993;McDonald et al, 1995), prevention of bone density loss (Love et al, 1992), sporadic excess of venous thromboembolism (Fisher et al, 1989;McDonald et al, 1995) and endometrial cancer (Rutqvist et al, 1987;Fisher et al, 1994) in adjuvant clinical trials.…”

mentioning

confidence: 99%

“…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). The observed lowering effect of tamoxifen on tHcy could therefore contribute further to explain the reduction in cardiovascular morbidity observed in some trials of adjuvant therapy (Rutqvist et al, 1993;McDonald et al, 1995). Because of the interest in assessing the effect of tamoxifen at the conventional dose of 20 mg day-' in the context of primary prevention, we measured plasma tHcy in a consecutive cohort of 66 healthy women enrolled in a double-blind, placebo-controlled prevention trial.…”

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confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

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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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“…1995. an effect that has been associated with a reduction in coronary heart disease in several adjuvant trials (Rutqvist et al 1993: McDonald et al 1995: Costantino et al 1997. Like oestrogen replacement therapy.…”

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confidence: 99%

“…tamoxifen may sporadically promote endometrial carcinorenesis (Fisher et al 1994. Rutqvist et al 1995 and deep venous thrombosis (Fisher et al 1989: McDonald et al 1995. Finally.…”

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confidence: 99%

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

et al. 1998

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Summary The combination of tamoxifen and transdermal hormone replacement therapy (HRT) may potentially reduce risks and side-effects of either agent, but an adverse interaction could attenuate their beneficial effects. We assessed the effects of their combination on cardiovascular risk factors within a prevention trial of tamoxifen. Baseline and 1 2-month measurements of total, low-density lipoprotein (LDL)-and high-density lipoprotein (HDL)-cholesterol, platelets and white blood cells were obtained in the following four groups: tamoxifen (n = 1117), placebo (n = 1112), tamoxifen and HRT (n = 68), placebo and HRT (n = 87). The analysis was further extended to women who were on HRT at randomization but discontinued it during the 12-month intervention period (n= 33 on tamoxifen and n = 35 on placebo) and to women who were not on HRT but started it during intervention (n = 36 in both arms of the study). Compared with small changes in the placebo group, tamoxifen was associated with changes in total, LDL-and HDL-cholesterol of approximately -90/, -19% and +0.2% in continuous HRT users compared with -9%/6, -14% and -0.8% in never HRT users. Similarly, there was no interaction on platelet count. In contrast, the decrease in total and LDL-cholesterol levels induced by tamoxifen was blunted by two-thirds in women who started HRT while on tamoxifen (P = 0.051 for the interaction term). We conclude that the beneficial effects of tamoxifen on cardiovascular risk factors are unchanged in current HRT users, whereas they may be attenuated in women who start transdermal HRT while on tamoxifen. Whereas a trial of tamoxifen in women already on transdermal HRT is warranted, prescription of HRT during tamoxifen may attenuate its activity.

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Individualizing Therapy to Prevent Long-term Consequences of Estrogen Deficiency in Postmenopausal Women

Col

Pauker²,

Goldberg³

et al. 1999

Arch Intern Med

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Cardiac and vascular morbidity in women receiving adjuvant tamoxifen for breast cancer in a randomised trial

Abstract: Our results provide further evidence that tamoxifen reduces the risk of myocardial infarction. Thromboembolic events should be carefully monitored in trials of tamoxifen, particularly those of prophylactic treatment, in which tamoxifen is given to healthy women.

Cited by 267 publications

References 8 publications

Tamoxifen reduces plasma homocysteine levels in healthy women

Tamoxifen reduces plasma homocysteine levels in healthy women

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

Individualizing Therapy to Prevent Long-term Consequences of Estrogen Deficiency in Postmenopausal Women

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