Endometrial Cancer in Tamoxifen-Treated Breast Cancer Patients: Findings From the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-14 *

Fisher, Bernard; Costantino, J. P.; Ck, Redmond; Er, Fisher; Dl, Wickerham; Wm, Cronin

doi:10.1093/jnci/86.7.527

Cited by 1,189 publications

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“…It is currently being evaluated as a chemopreventive agent in young healthy women at high risk for breast cancer (Powles et al, 1990;Nay®eld et al, 1991). One of the most signi®cant complications of long term tamoxifen use is the development of endometrial cancer with up to a 7.5-fold increase in risk (Barakat, 1996;Fisher et al, 1994;Rutqvist et al, 1995). Tamoxifen treatment has also been implicated in the development of endometrial polyps and endometrial hyperplasia (Gal et al, 1991;Lahti et al, 1993;Kedar et al, 1994).…”

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confidence: 99%

PCR display identifies tamoxifen induction of the novel angiogenic factor adrenomedullin by a non estrogenic mechanism in the human endometrium

et al. 1998

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Tamoxifen is currently the most widely used drug for the treatment of breast cancer, but there now exists considerable evidence that tamoxifen can also induce endometrial hyperplasia in pre menopausal women. We have used PCR di erential display on primary human endometrial isolates in an attempt to identify genes induced by tamoxifen but not estrogen. Eight such di erentially expressed bands were cloned and sequenced, one of which was found to be the peptide adrenomedullin. We have shown that adrenomedullin is a novel growth factor for endothelial cells and is angiogenic in vivo in the chick chorioallantoic membrane assay. Immunohistochemical analysis of endometrial sections have shown that while macrophages in the endometrium express adrenomedullin at a low level, endometrial macrophages of women receiving tamoxifen strongly express adrenomedullin (P=0.008). We postulate that endometrial induction of the angiogenic factor adrenomedullin by tamoxifen is part of the mechanism by which tamoxifen results in endometrial hyperplasia.

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Section: Introductionmentioning

confidence: 99%

PCR display identifies tamoxifen induction of the novel angiogenic factor adrenomedullin by a non estrogenic mechanism in the human endometrium

et al. 1998

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“…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.…”

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confidence: 99%

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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“…Like oestrogen replacement therapy. 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.…”

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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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Endometrial Cancer in Tamoxifen-Treated Breast Cancer Patients: Findings From the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-14 *

Abstract: Tamoxifen treatment for breast cancer should continue. In addition, the relative risk of endometrial cancer observed in B-14 tamoxifen-treated patients is consistent with the twofold relative risk used in the initial risk-benefit computation for the NSABP breast cancer prevention trial.

Cited by 1,189 publications

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PCR display identifies tamoxifen induction of the novel angiogenic factor adrenomedullin by a non estrogenic mechanism in the human endometrium

PCR display identifies tamoxifen induction of the novel angiogenic factor adrenomedullin by a non estrogenic mechanism in the human endometrium

Tamoxifen reduces plasma homocysteine levels in healthy women

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

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