Tamoxifen and the Uterus and Endometrium

Neven, Patrick; Muylder, X. De; Belle, Yves Van; Vanderick, G.; Muylder, E. De; Stewart, H.J.; Knight, GillianM.; Cano, Antonio; Matallin, Pilar; Legua, V.; Tortajada, Miguel; Bonilla‐Musoles, Fernando

doi:10.1016/s0140-6736(89)91741-8

Cited by 183 publications

(61 citation statements)

References 8 publications

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“…Endometrial changes One of the main adverse effects that tamoxifen-treated breast cancer patients experience is an increased risk of developing endometrial hyperplasia, polyps, and carcinoma (Fornander et al 1989, Neven et al 1989, Rutqvist & Johansson 2007. Patients treated with tamoxifen have a two-to three-times higher risk of developing endometrial cancer compared with individuals receiving placebo (Fisher et al 1998).…”

Section: New Indicationsmentioning

confidence: 99%

Aromatase inhibitors in the breast cancer clinic: focus on exemestane

Asten¹,

Neven²,

Lintermans³

et al. 2014

Endocrine-Related Cancer

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Breast cancer is the most prevalent type of cancer in women and responsible for significant female cancer-related mortality worldwide. In the Western world, over 80% of breast cancers are hormone-receptor positive for which endocrine therapy is administered. The main anti-estrogen treatments in use consist of selective estrogen-receptor modulators, such as tamoxifen, and third-generation aromatase inhibitors (AIs), such as exemestane, letrozole, and anastrozole. In this review, the focus will lie on exemestane, its clinical use, and its side-effect profile. Exemestane is the only third-generation steroidal AI. Its efficacy as a first-line treatment in metastatic breast cancer has been demonstrated. Therefore, exemestane could be considered a valid first-line therapeutic option, but it also can be used in second-line or further situations. Exemestane is mostly used as part of sequential adjuvant treatment following tamoxifen, but in this setting it is also active in monotherapy. Furthermore, this AI has been studied in the neoadjuvant setting as presurgical treatment, and even as chemoprevention in high-risk healthy postmenopausal women. It may reverse side effects of tamoxifen, such as endometrial changes and thromboembolic disease but may also cause some inconvenient side effects itself. Additionally, there is a lack of total crossresistance between exemestane and nonsteroidal AIs as far as their anti-tumoral efficacy is concerned; moreover the two classes of AIs display a nontotal overlapping toxicity profile. Taking together, exemestane can be considered as a useful treatment option at all stages of breast cancer.

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Section: New Indicationsmentioning

confidence: 99%

Aromatase inhibitors in the breast cancer clinic: focus on exemestane

Asten¹,

Neven²,

Lintermans³

et al. 2014

Endocrine-Related Cancer

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“…In other organs like bone, uterus, pituitary and liver, its interaction with the ER may induce estrogen agonistic effects. After menopause, it increases bone mineral density and endometrial thickness with an increased risk to develop endometrial hyperplasia, polyps and even cancer [3]. Its estrogenic effect on the postmenopausal pituitary and liver, respectively, lowers circulating follicle-stimulating hormone (FSH) and increases sex hormone-binding globulin (SHBG) [4].…”

Section: Introductionmentioning

confidence: 99%

“…Absence of such an effect in a poor metabolizer may be another proof that the drug is not metabolized with the potential for this marker to serve as an early surrogate for poor treatment outcome. It is well known that tamoxifen intake induces uterine abnormalities like endometrial polyps, endometrial thickening and subepithelial cysts in a large proportion of postmenopausal tamoxifen users early in treatment [3,28]. Also, tamoxifen leads to a decrease in serum levels of FSH and increase in serum levels of SHBG in postmenopausal women [4].…”

mentioning

confidence: 99%

Prevalent breast cancer patients with a homozygous mutant status for CYP2D6*4: response and biomarkers in tamoxifen users

Dieudonné

Lambrechts

Claes

et al. 2009

Breast Cancer Res Treat

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Retrospective studies suggest that single nucleotide polymorphisms in the cytochrome P450 2D6 (CYP2D6) gene predict reduced tamoxifen metabolism, better tolerance and worse treatment outcome. We hypothesized that women with this genotype lack tamoxifen-induced endometrial and biochemical changes in follicle-stimulating hormone (FSH) and sex hormone-binding globulin (SHBG). We identified 56 breast cancer patients attending the follow-up clinic with a homozygous mutant (HM) status for the CYP2D6*4 null variant. Here, we report a detailed assessment of tamoxifen activity in 19 CYP2D6 HM women, while they were using tamoxifen either for metastatic (n = 5) or for early disease (n = 14). We assessed response to tamoxifen in metastatic disease. Endometrial appearances and serum levels of FSH and SHBG were assessed from retrospective and prospective testing. Our findings do suggest that the presence of two CYP2D6*4 alleles does not exclude a durable response of tamoxifen in metastatic breast cancer. The transvaginal ultrasonographic appearance of the endometrium in CYP2D6*4/*4 patients on tamoxifen is similar as seen in the normal population of tamoxifen users. The endometrium is increased in thickness with subepithelial cysts and endometrial polyps. Serum levels of FSH and SHBG in CYP2D6*4 HM tamoxifen users were in the range of what would be expected during tamoxifen treatment in the general population. Our findings do show CYP2D6*4/*4 carriers to have activity of tamoxifen on breast cancer, endometrium and serum levels of FSH and SHBG. They support clinical trials prospectively testing the effect of CYP2D6 genetic variability in response to tamoxifen before denying this drug to breast cancer patients only based on their CYP2D6*4 status.

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“…Tamoxifen administration is known to be associated with gynecological side effects such as endometrial hyperplasia, polyps and cancer [1][2][3][4]. Although most of these changes are benign, the wide range of abnormalities induced by tamoxifen has led to a number of gynecological interventions in symptomatic women to exclude malignant disease.…”

Section: Introductionmentioning

confidence: 99%

Prospective assessment of the endometrium in postmenopausal breast cancer patients treated with fulvestrant

Morales

Neven

Timmerman

et al. 2008

Breast Cancer Res Treat

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This prospective study assessed the endometrial effects of fulvestrant, a pure estrogen-receptor antagonist, in postmenopausal women with breast cancer. This singlecenter study enrolled postmenopausal patients who had an intact uterus at baseline with progressive metastatic breast cancer on tamoxifen followed by an oral aromatase inhibitor (AI). Fulvestrant (250 mg) was administered every 28 ± 3 days via IM injection. Transvaginal ultrasonography (TVUS) was performed at baseline and after 3 months of therapy. Primary and secondary endpoints were changes from baseline in double endometrial thickness (DET) and uterine volume (UV), respectively. No interventions were performed on any asymptomatic uterine abnormalities that were detected at baseline. In total, 32 women were enrolled. Five patients had no repeat TVUS because of early progression before 3 months, leaving 27 evaluable patients for final analysis. After 3 months therapy, mean DET had significantly decreased by 23.08% (P = 0.010). Mean UV also decreased by 10.88%, although this change was not significant (P = 0.119). After 3 months of therapy, none reported vaginal bleeding, there were no changes noted in most of the uterine pathologies present at baseline and no new uterine abnormalities were detected. We observed that 3 months of fulvestrant treatment resulted in a significant decrease in endometrial growth and a non-significant decrease in UV in postmenopausal women with metastatic breast cancer previously exposed to tamoxifen and AIs. Furthermore, no new uterine pathologies were detected, indicating that fulvestrant behaves as a pure antiestrogen at the uterine level.

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Tamoxifen and the Uterus and Endometrium

Cited by 183 publications

References 8 publications

Aromatase inhibitors in the breast cancer clinic: focus on exemestane

Aromatase inhibitors in the breast cancer clinic: focus on exemestane

Prevalent breast cancer patients with a homozygous mutant status for CYP2D6*4: response and biomarkers in tamoxifen users

Prospective assessment of the endometrium in postmenopausal breast cancer patients treated with fulvestrant

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