Endometrial disorders in 406 breast cancer patients on tamoxifen: the case for less intensive monitoring

Vosse, Marianne; Renard, Françoise; Coibion, Michel; Neven, P.; Nogaret, Jean-Marie; Hertens, Dina

doi:10.1016/s0301-2115(01)00516-4

Cited by 61 publications

(20 citation statements)

References 25 publications

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“…Despite its high therapeutic index, TAM has been associated with a twofold risk increase in endometrial cancer (Houssami et al 2006) and can stimulate endometrial growth and hyperplasia in postmenopausal women (Kedar et al 1994, Vosse et al 2002. TAM induces uterotrophy in immature and ovariectomized rodents and elicits a gene expression profile similar to estrogen in uterine tissue, albeit with lower efficacy (Hodges et al 2003, Frasor et al 2004, Fong et al 2007, Kwekel et al 2009).…”

Section: Introductionmentioning

confidence: 99%

Effects of tamoxifen and ethynylestradiol cotreatment on uterine gene expression in immature, ovariectomized mice

Fong

Burgoon

Williams³

et al. 2010

Journal of Molecular Endocrinology

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Tamoxifen (TAM), the primary treatment for estrogen receptor (ER)-positive breast cancer, has been associated with an increased incidence of endometrial cancer in postmenopausal, but not premenopausal women. TAM elicits a partial ER-mediated uterotrophic response in immature rodents when compared with ethynylestradiol (EE), a potent ER agonist. However, cotreatment with 1000 mg/kg TAM antagonizes the uterotrophic effect induced by 30 mg/kg EE. To further investigate the anti-uterotrophic activity of TAM, immature, ovariectomized C57BL/6 mice were treated with a single oral dose of EE, TAM, EECTAM, or vehicle, and harvested at 2, 4, 8, 12, 18, and 24 h or after three daily treatments at 72 h. Significant increases in uterine wet weight (UWW) were observed at 18 h for EE, TAM, and the mixture. However, mixture induction of UWW was significantly lower when compared with EE-induced uterotrophy at 72 h. This inhibitory effect is also reflected in decreases in luminal circumference, yet EE-induced luminal epithelial cell height was unaffected by cotreatment with TAM. Gene expression analysis using a 2!2 factorial cDNA microarray study design identified 2518 differentially expressed genes following EE treatment alone. However, only 290 EE-elicited gene expression changes were affected by TAM cotreatment, in a manner consistent with the anti-estrogenic response. These data suggest that TAM antagonism of EE-induced UWW increase involves the selective inhibition of EE-induced genes.

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Section: Introductionmentioning

confidence: 99%

Effects of tamoxifen and ethynylestradiol cotreatment on uterine gene expression in immature, ovariectomized mice

Fong

Burgoon

Williams³

et al. 2010

Journal of Molecular Endocrinology

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“…This is consistent with reports in the literature that polyps occurred more frequently in women with initial lesions prior to tamoxifen treatment. 3,[17][18][19] Therefore, a baseline endometrial assessment prior to tamoxifen is recommended.…”

Section: Discussionmentioning

confidence: 99%

“…[2][3][4] The incidences of endometrial polyps, hyperplasia and endometrial cancer had been reported to be between 5 and 35%, 4.7-16% and 0.8-5%, respectively. [2][3][4] However, only 2% of endometrial pathology and <50% of endometrial cancer presented with symptoms at diagnosis. 4 Therefore, endometrial surveillance is recommended for women receiving tamoxifen.…”

Section: Introductionmentioning

confidence: 99%

A randomised controlled trial of prophylactic levonorgestrel intrauterine system in tamoxifen‐treated women

Chan¹,

Tam²,

Park³

et al. 2007

BJOG

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Objective To study the prophylactic use of levonorgestrel intrauterine system (LNG-IUS) in the prevention of endometrial pathology in women having breast cancer treated with tamoxifen.Design Randomised controlled trial.Setting A tertiary teaching hospital.Population One hundred and thirteen women (66 premenopausal/ 47 postmenopausal) who required adjuvant tamoxifen for breast cancer after the completion of postoperative radiotherapy and chemotherapy.Methods Women were randomised to treatment group (prophylactic LNG-IUS insertion before the commencement of tamoxifen) or control group. Uterine cavity was examined by outpatient hysteroscopy and endometrial biopsy before and at 12 months after commencement of tamoxifen.Main outcome measures De novo endometrial pathology at 1 year of tamoxifen.Results Women in the treatment group had a much lower incidence of endometrial polyp (1.8 versus 15.5%, P = 0.017) (relative risk: 0.12; 95% CI: 0.02-0.91) at 12 months. There was no significant difference in the incidence of submucosal fibroid between the two groups (1.8 versus 3.4%, P = 1.0). LNG-IUS was retained in 95% women in the treatment group at 1 year.Conclusion LNG-IUS reduces the occurrence of de novo endometrial polyp in women treated with tamoxifen for breast cancer.Keywords Breast cancer, endometrial polyps, levonorgestrel intrauterine system, tamoxifen.Please cite this paper as: Chan S, Tam W, Yeo W, Yu M, Ng D, Wong A, Kwan W, Yuen P. A randomised controlled trial of prophylactic levonorgestrel intrauterine system in tamoxifen-treated women. BJOG 2007;114:1510-1515

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“…However, the well-known SERMs, raloxifene and tamoxifen, have been reported to decrease the risk of breast cancer and increase bone mineral density, but they have also been associated with the stimulation of endometrial growth, the occurrence of hot flashes and an increased risk of venous thromboembolism (Barrett-Connor et al, 2006;Cranney and Adachi, 2005;Delmas et al, 1997;MacGregor and Jordan, 1998;Vosse et al, 2002;Zidan et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Bioactivity guided isolation of phytoestrogenic compounds from Cyclopia genistoides by the pER8:GUS reporter system

Roza

Lai

Zupkó

et al. 2017

South African Journal of Botany

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The popular South African herbal tea, honeybush, is made from several Cyclopia species (family: Fabaceae), amongst them Cyclopia genistoides. Phytoestrogenic potential of C. genistoides. has been recently reported, however bioactivity-guided isolation of compounds with estrogenic activity has not yet been performed. A transgenic plant system, Arabidopsis thaliana pER8:GUS, was used to assay the estrogen-like activity of C. genistoides. The quantitative determination of the active compounds in the fermented and non-fermented plant material was performed by HPLC. Subsequent bioactivity-guided fractionation led to the isolation of genistein, naringenin, isoliquiritigenin, luteolin, helichrysin B and 5,7,3′,5′-tetrahydroxyflavanone, four of them first reported in the genus. Helichrysin B, naringenin and 5,7,3′,5′-tetrahydroxyflavanone differed in quantity in the fermented and unfermented herbs, the fermented plant material contained two compounds with substantial estrogenic-like activity in higher concentration (naringenin and 5,7,3′,5′-tetrahydroxyflavanone), whereas the less active helichrysin B was more abundant in the unfermented herb. The fractions as well as compounds inhibited the growth of human cancer cell lines A2780 and T47D. These results underline the phytoestrogenic activity of C. genistoides and support the rationale to the fermentation process.

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Endometrial disorders in 406 breast cancer patients on tamoxifen: the case for less intensive monitoring

Cited by 61 publications

References 25 publications

Effects of tamoxifen and ethynylestradiol cotreatment on uterine gene expression in immature, ovariectomized mice

Effects of tamoxifen and ethynylestradiol cotreatment on uterine gene expression in immature, ovariectomized mice

A randomised controlled trial of prophylactic levonorgestrel intrauterine system in tamoxifen‐treated women

Bioactivity guided isolation of phytoestrogenic compounds from Cyclopia genistoides by the pER8:GUS reporter system

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