Tamoxifen and the endometrium: findings of pelvic ultrasound examination and endometrial biopsy in asymptomatic breast cancer patients.

Divisione di Oncologia Medica 1, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
Breast Cancer Research and Treatment (Impact Factor: 3.94). 01/1998; 47(1):41-6.
Source: PubMed


The need for endometrial surveillance in breast cancer patients undergoing adjuvant treatment with tamoxifen is still controversial. In this study, 164 asymptomatic breast cancer patients (110 on treatment with tamoxifen, 20 mg/day, and 54 controls) were examined with pelvic ultrasound and endometrial biopsy. No differences in ultrasound and biopsy findings were observed in the pre- and perimenopausal group between patients treated with tamoxifen and controls. Postmenopausal patients on tamoxifen had a significantly thicker endometrium (mean+/-SD, 7.2+/-8.5 vs. 1.5+/-4.3 mm, p=0.00002) and significantly larger uterine volume (mean+/-SD, 63.2+/-39.9 vs. 43.7+/-38.8 cm3, p=0.0001) than controls. Fifty-four percent of patients on tamoxifen had an endometrial thickness > or = 5 mm, often with multiple irregular sonolucencies suggesting the presence of cysts. Ultrasound findings, however, did not correlate with the presence of endometrial abnormalities on biopsy, and no endometrial cancer or atypical hyperplasia were found. This lack of correlation makes questionable the use of routine sonography in asymptomatic breast cancer patients on tamoxifen. Obtaining routine endometrial samples, on the other hand, may be difficult in some patients because of cervical stenosis or refusal. Until the benefits of endometrial surveillance will be proved, asymptomatic patients should not be submitted routinely to ultrasound examination or biopsy, but encouraged to report promptly any abnormal vaginal bleeding.

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    • "Interestingly, our patient had a negative preoperative EMB but surgical pathology revealed endometrial neoplasm (CAH), supporting the hypothesis that the sensitivity of an EMB for detecting neoplasia in asymptomatic women is less than that in women experiencing abnormal vaginal bleeding. Similarly, endometrial screening in asymptomatic breast cancer patients taking tamoxifen with routine transvaginal ultrasound, EMB, or both was not more effective than evaluation at the time of abnormal bleeding (Bertelli et al., 1998; Fung et al., 2003). Given the uncertainty over the efficacy of endometrial cancer screening in asymptomatic women, a cornerstone of preventive gynecologic care for women with CS and LS should be careful patient education on the recognition of abnormal uterine bleeding and the need for prompt evaluation of new symptoms with EMB. "
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    ABSTRACT: Fig. 1. A. Hematoxylin and eosin (H&E) stained section of complex atypical hyperplasia of the endometrium identified incidentally at prophylactic hysterectomy. B. H&E stained section from excisional breast biopsy demonstrating atypical hyperplasia. C–H. Sanger sequencing traces of PTEN at the site of the N48K mutation, c.144C > A, identified with arrow. C. Loss of the wildtype PTEN allele in DNA from microdissected epithelium from complex endometrial hyperplasia. D. Retention of both wildtype and mutant PTEN alleles in normal endometrial epithelium and in normal endometrial stroma (E). F. Loss of the wildtype PTEN allele in DNA from microdissected epithelium atypical breast hyperplasia. G. Retention of both wildtype and mutant PTEN alleles in normal breast epithelium and in normal breast stroma (H).
    02/2015; 12. DOI:10.1016/j.gore.2015.01.008
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    • "In a study of 164 asymptomatic women with previous breast cancer and TAM treatment, Bertelli et al. (1998) reported no correlation between endometrial thickness R5 mm (54% of patients) and endometrial atypia. The authors concluded that in the absence of symptoms, it is not recommended to base routine follow-up on ultrasound and biopsy. "
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    ABSTRACT: Objective:To determine the role, timing and indications for endometrial hysteroscopic investigation in relation to the clinical, ultrasound and histological features of the endometrium during tamoxifen use.Methods:We performed an observational longitudinal cohort study (years 2007-2012) that investigated the endometria of 151 tamoxifen users with hysteroscopy and histology. For all patients, gynaecological history, years of adjuvant treatment, ultrasound endometrial thickness measurement and indications for hysteroscopy were recorded.Results:Hysteroscopic findings showed that 100% of patients referred for simple follow-up had no evidence of endometrial disease. We found a strong correlation between previous history of abnormal uterine bleeding (with or without endometrial thickening) and hysteroscopic suspicion of endometrial atypia that was confirmed by histology.Hysteroscopy had 83.3%-sensitivity, 99%-specificity, 83.3%-PPV and 99%-NPV in detecting endometrial atypia. No significant correlation was found between endometrial thickening to >5mm without bleeding and histological atypia. Similarly, the duration of treatment was not related to endometrial thickening and histological atypia.Endometrial stromal hyperplasia was detected by histology in 70.5% of patients with endometrial thickness measurements ranging from 5-10 mm. In contrast, no atypia was detected when endometrial thickness was <5mm.Ultrasound performed using a 5-mm cut-off threshold for endometrial thickness resulted in 100%-sensitivity, 15%-specificity, 4%-PPV and 100%-NPV in detecting endometrial atypia, while a 10-mm cut-off threshold resulted in 84%-sensitivity, 69%-specificity, 10%-PPV and 99%-NPV.Conclusion:Low-risk tamoxifen users do not require different endometrial surveillance than the general population. Hysteroscopy could play a fundamental role in determining the endometrial status of patients before the initiation of tamoxifen treatment and in assessing the endometrial status of patients when bleeding occurs.
    Endocrine Related Cancer 04/2013; 20(4). DOI:10.1530/ERC-13-0020 · 4.81 Impact Factor
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    • "These SERMs offer additional beneficial effects of oestrogen, for example tamoxifen lowers cholesterol (Love et al., 1994). However novel SERMs are sought due to drawbacks with current SERMs, for example, tamoxifen promotes excessive endometrial growth in the uterus which increases the risk of uterine cancer (Bertelli et al., 1998) and all the three prescribed SERMs have been associated with venous thromboembolism and hot flushes (Morello et al., 2002). On the other hand, both LY362321 (Farr et al., 2008) and LY2120310 (personal communication with Dr. M. O'Neill and Dr. J. Dodge at Eli Lilly) have high affinity to ER␣ and ER␤, are potent antagonists to uterine tissue, prevent ovariectomy-induced bone loss and have physicochemical characteristics of a highly brain penetrable compound and have effective dose ranges of 1–10 mg/kg and 0.3–10 mg/kg, respectively. "
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    ABSTRACT: Cerebrovascular disorders are less common in pre-menopausal than post-menopausal women and in females than males. This protection may be due, in part at least, to direct effects of oestrogens on blood vessels. Oestrogen's vasodilatory mechanisms have been reported to be via the endothelium, vascular smooth muscle and extracellular matrix, depending on the vascular bed studied. Herein we investigated the vasoactive effects of oestrogen, oestrogen receptor (ER) and GPR30 agonists and selective ER modulators (SERMs) in the rat middle cerebral artery(MCA), an artery affected in focal ischaemia. MCAs isolated from male Sprague Dawley rats were mounted on a wire myograph. Concentration response curves were constructed to 17β-oestradiol, ERα agonist-PPT, ERβ agonist-DPN, GPR30 agonist-G1 and novel SERMs (LY362321 and LY2120310) in pre-constricted vessels, in the presence and absence of endothelium, blocking agents for nitric oxide synthase (L-NAME), classic ER antagonist (ICI182,780) or plasma membrane specific ERα (ERα-36) antibody. 17β-oestradiol induced rapid vasorelaxation of the MCA which was not affected by endothelium removal, L-NAME or ICI182,780. Vasorelaxation was mimicked by PPT, DPN and G1 but not by the SERMs. Using ERα-36 antibody, effects of oestrogen were partially blocked. PPT had a greater vasorelaxation, while DPN and G1 had a lesser effect than 17β-oestradiol. These findings indicate that activation of plasma membrane bound ERα, β and GPR30 elicits rapid, endothelial-nitric oxide-independent relaxation of the rat MCA.
    Neuroscience Research 05/2011; 71(1):78-84. DOI:10.1016/j.neures.2011.05.006 · 1.94 Impact Factor
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