Endometrial lesions in patients undergoing tamoxifen therapy

Muylder, X. De; Neven, Patrick; Somer, M. De; Belle, Yves Van; Vanderick, G.; Muylder, E. De

doi:10.1016/0020-7292(91)90767-y

Cited by 113 publications

(50 citation statements)

References 7 publications

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“…There have been many reports of abnormalities identified in the endometrium in women on tamoxifen including hyperplasia with atypia and polyps, some of which are similar to the changes seen with ERT (Cross and Ismail, 1990;Neven et al, 1990;De Muylder et al, 1991;Cohen et al, 1993;Lahti et al, 1993;Neven, 1993;Ismail, 1994;Aleem and Predanic, 1995).…”

mentioning

confidence: 92%

The effects of norethisterone on endometrial abnormalities identified by transvaginal ultrasound screening of healthy post-menopausal women on tamoxifen or placebo

Powles

Bourne²,

Athanasiou³

et al. 1998

Br J Cancer

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Summary Tamoxifen (tam) is used extensively for treatment of patients with breast cancer and is being evaluated for chemoprevention in healthy women. It has, however, been reported to increase the risk of endometrial cancer in post-menopausal women, probably by an oestrogenic effect on the endometrium. It also causes endometrial cysts and polyps. The aims of this study were to identify the incidence of endometrial thickening, polyps and cysts by transvaginal ultrasound (TVUS) screening of a population of post-menopausal healthy women in the Royal Marsden tamoxifen chemoprevention trial and to evaluate the possible benefit from the use of intermittent norethisterone (NE) in women with persistent changes. Since 1990, we have undertaken regular TVUS, using an endovaginal B mode probe, of the 463 postmenopausal women in the trial randomized to tam (20 mg day-') or placebo (plac), without breaking the randomization code. Endometrial thickening (ET) was defined as .8 mm at the widest point across the myometrial cavity in the longitudinal plane, including any stromal changes. Cystic changes were defined as more than one hypoechogenic area > 1 mm. Polyps were identified using saline hydrosonography. Oral NE (2.5 mg day-1) was used for 21 days out of 28 for three consecutive cycles by women with persistent endometrium . 8 mm, including cystic and polypoid changes. TVUS was repeated after the three courses to evaluate any change caused by NE and endometrial biopsies, including hysteroscopy, was performed on those women with persistent abnormalities. A persistent ET . 8 mm was identified in 56 (24%) of the 235 women on tamoxifen compared with only 5 (2%) of 228 women on placebo (P <0.0005). Stromal changes, including cysts, were detected in 36 (15%) and polyps in 26 (11%) of the women on tamoxifen compared with only two (<1%) of the women on placebo (P << 0.0005). After 3 months of cyclical norethisterone, 39 of 47 women (83%) on tamoxifen had persistent ultrasound changes. However, 45 (96%) had a progesterone withdrawal bleed. Hysteroscopy was performed in 39 women on tamoxifen (28 endometrial biopsy, 15 polypectomy), five of whom had histological evidence of a proliferative endometrium and a further three had an atypical hyperplastic endometrium (one of whom had a focus of invasive carcinoma). The cysts and polyps which were detected in women on tam could not be reversed by NE and were presumably stromal and not of malignant risk. However, 96% of the women had withdrawal NE bleeding, indicating an oestrogenically primed endometrium which could be a mechanism for an increased risk of endometrial cancer. Further studies are required to ascertain whether a progestin would protect against this risk. As in other studies, these results indicate that any increased risk of endometrial cancer caused by tamoxifen is low, and that TVUS screening is probably not justified for asymptomatic women on tamoxifen. Group, 1992). Based on these findings, it is now widely used and many millions of women have had, or are now receiving, such ...

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confidence: 92%

The effects of norethisterone on endometrial abnormalities identified by transvaginal ultrasound screening of healthy post-menopausal women on tamoxifen or placebo

Powles

Bourne²,

Athanasiou³

et al. 1998

Br J Cancer

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“…Nowadays, more than 1 in 20 female cancers in Europe are of the endometrium. [1][2][3][4][5][6][7][8][9][10] Contrary to cervical carcinoma, no screening programs have been organized for the early detection of endometrial adenocarcinoma. The lack of screening programs may be related to the precocious presenting symptoms and to the relative good prognosis of the majority of endometrial adenocarcinomas.…”

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confidence: 99%

Liquid‐based endometrial cytology in the management of sonographically thickened endometrium

Buccoliero

Gheri

Castiglione

et al. 2007

Diagnostic Cytopathology

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Liquid-based cytology represents an opportunity to re-evaluate endometrial cytology. We evaluated the accuracy of liquid-based endometrial cytology as compared to biopsy in 670 women scheduled for histeroscopy because of thickened endometrium (>4 mm), as evaluated by transvaginal sonography. Endometrial biopsy detected pathology in 41 (6%) of cases (21 of which were adenocarcinomas). Cytologic study found pathology in 62 (9%) cases (19 of which were adenocarcinomas). Two hundred ninety-one biopsies (43%) and 28 (4%) cytologies were inadequate. The sensitivity and the specificity were estimated, respectively, at 95% and 98%; the positive and negative predictive values were estimated, respectively, at 83% and 99%. Cytology provided sufficient material more often than biopsy (P < 0.01). We consider endometrial cytology an efficacious diagnostic opportunity. It could be usefully applied in association with transvaginal sonography. The combination of these procedures might reduce more invasive and expensive diagnostic procedures. Diagn. Cytopathol. 2007;35:398-402. ' 2007 Wiley-Liss, Inc.Key Words: thin-layer; liquid-based; endometrial cytology; endometrial adenocarcinoma; endometrial hyperplasia Endometrial adenocarcinoma is the most common malignancy of the female genital tract. A significant increase in its frequency, both absolute and relative, has been observed during the last decades. This increase is considered the consequence of the extended life expectancy of women, the increase in the incidence of risk factors, and of the reduction of invasive cervical carcinomas. Nowadays, more than 1 in 20 female cancers in Europe are of the endometrium. [1][2][3][4][5][6][7][8][9][10] Contrary to cervical carcinoma, no screening programs have been organized for the early detection of endometrial adenocarcinoma. The lack of screening programs may be related to the precocious presenting symptoms and to the relative good prognosis of the majority of endometrial adenocarcinomas. Early abnormal uterine bleeding, the commonest presenting symptom for the 95% of women, allows diagnosis at stage I in 73% of cases. 11 Moreover, there has not been an endometrial test comparable to cervicovaginal cytology for diagnostic reliability, tolerability, and low cost.Several diagnostic procedures are used for investigating the endometrium, but there is no common agreement for the optimum approach in each circumstance (i.e. symptomatic vs. asymptomatic; with risk factors vs. without risk factors).Endometrial cytology has been hampered in its dissemination by the difficulty in its interpretation due to the common presence of excess blood and overlapping cells. Liquid-based cytology represents an opportunity to reexamine endometrial cytology. We conducted the current study to correlate the results of liquid-based endometrial cytology with the results of endometrial biopsy in a group of 670 women scheduled for hysteroscopy because of thick endometrium (>4 mm), as evaluated by transvaginal sonography (TVS). Our purpose was preliminarily to asce...

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“…[2][3][4][5][6][7] In postmenopausal women tamoxifen exerts a proliferative effect on the endometrium, as measured by the hyperdiploid fraction, 8 and clinical studies have reported an increased incidence of endometrial polyps and hyperplastic endometrial changes, mostly interpreted as evidence of the agonistic effect of tamoxifen. [9][10][11][12][13][14] Histology of tamoxifen exposed postmenopausal endometrium in general shows a characteristic picture of a condensated, hypercellular, collagen rich stroma, whereas the glandular epithelium stays thin and atrophic or metaplastic, the flattened epithelium lining cystically dilated glands or polyps. 8 13 15 The incidence of benign, tamoxifen induced changes by far exceeds the incidence of endometrial cancer, 14 suggesting that most of these endometrial changes do not progress to cancer.…”

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confidence: 99%

The effects of tamoxifen on proliferation and steroid receptor expression in postmenopausal endometrium

Mourits¹,

Hoor²,

Zee

et al. 2002

Journal of Clinical Pathology

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Aim: To study the effects of tamoxifen on the proliferation index and oestrogen receptor (ER) and progesterone receptor (PR) expression in postmenopausal endometrium. Methods: A total of 125 endometrial specimens of postmenopausal women, comprising benign endometria from tamoxifen users (n = 35) and non-users (n = 24), and endometrial cancer from tamoxifen users (n = 15) and non-users (n = 51), were immunohistochemically examined using MIB-1, anti-ER, and anti-PR antibodies in endometrial epithelium and stroma. Results: In benign endometrium the mean MIB-1 index in the epithelium was higher in tamoxifen users than in non-users (mean, 13% (SD, 13%) v mean, 2% (SD, 2%); p < 0.05), whereas in endometrial cancer the MIB-1 index was higher, but similar in tamoxifen users and non-users (mean, 32% (SD, 24%) and mean, 35% (SD, 18%)). The expression of ER was comparably high in benign epithelium from tamoxifen users and non-users (97% and 92%, respectively), but in endometrial cancer it was lower in tamoxifen users (60% and 88%; p < 0.05). The expression of PR in stromal cells was higher in tamoxifen users, both in benign (84% v 54%) and in malignant endometrium (33% v 10%; p < 0.05). Conclusion:The proliferation index (as measured by MIB-1) in benign endometrial epithelium is higher in tamoxifen users than in non-users, and this might play a role in the reported higher incidence of endometrial cancer in postmenopausal tamoxifen users. The increased expression of PR in stroma from tamoxifen users with both benign and malignant endometrium demonstrates an additional oestrogenic effect of tamoxifen on the endometrial stroma.

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Endometrial lesions in patients undergoing tamoxifen therapy

Cited by 113 publications

References 7 publications

The effects of norethisterone on endometrial abnormalities identified by transvaginal ultrasound screening of healthy post-menopausal women on tamoxifen or placebo

The effects of norethisterone on endometrial abnormalities identified by transvaginal ultrasound screening of healthy post-menopausal women on tamoxifen or placebo

Liquid‐based endometrial cytology in the management of sonographically thickened endometrium

The effects of tamoxifen on proliferation and steroid receptor expression in postmenopausal endometrium

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