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© 2000 American Society for Clinical Oncology
Tamoxifen and Endometrial ScreeningUniversity of Groningen Groningen, The Netherlands To the Editor:In their article in July 1999 issue of the Journal of Clinical Oncology, Love et al1 described an abnormal cystic thickening of the endometrium on transvaginal ultrasound (TVU) in 41% of asymptomatic, tamoxifen-treated patients, of whom 46% were found to have atrophic endometrium at hysteroscopy. In an attempt to give an explanation for the thickened endometrium on TVU, Love et al referred to publications in which it was suggested that endometrial serosa or myometrial edema might cause the sonographic changes. They also state that there is "no exact pathologic correlation for these findings." In his editorial in the same issue, Barakat2 reports on the study of Goldstein,3 who described irregular thickening of the endometrium on TVU in five patients and interpreted the findings at subsequent sonohysterography as subendometrial abnormalities representing adenomyomatous-like changes in the myometrium of the hysterectomy specimens. In a recent study, we reported a histopathologic explanation for the misleading ultrasound appearance of the endometrium in tamoxifen users.4 In 53 asymptomatic, postmenopausal, tamoxifen-treated breast cancer patients, TVU was performed. In 25 patients with an endometrial thickness greater than 5 mm, a hysteroscopy was performed. Endometrial polyps were found in seven patients, while in the other 18, hysteroscopy showed only atrophic endometrium. In concordance with the report of Love et al, despite attempted biopsies and curettages, we were unable to obtain tissue from the atrophic endometrium. In three patients with negative hysteroscopy results, a hysterectomy was performed for other reasons. The histologic characteristics of the endometrium in the hysterectomy specimens resembled those of the endometrial polyps: cystically dilated glands lined with flattened epithelium were surrounded by dense, condensated endometrial stroma, thus resembling Swiss cheese. This characteristic histology, also referred to as glandulocystic atrophy, has also been described by others.5 To distinguish endometrium from myometrium, a desmin staining was performed. The measured thickness of the endometrium at microscopy corresponded well with the thickness at TVU as determined before hysterectomy. On the basis of these data, we conclude that a thickened, cystic endometrium in postmenopausal tamoxifen-treated patients should not be ascribed to myometrial or subendometrial changes, but these changes are located within the endometrium: the dense endometrial stroma causes the enhanced echogenicity, and the fluid-filled, dilated, atrophic glands cause the echolucent areas on ultrasound (Fig 1).
Recommendations regarding endometrium screening in tamoxifen-treated patients are given by both Love et al1 and Barakat.2 Because of the high false-positive rate of endometrial sonographic screening and the low frequency of significant findings at hysteroscopy, Love et al conclude that endometrial screening in asymptomatic patients is not warranted. In his editorial, Barakat affirms this statement. Nevertheless, in the last paragraph of his editorial, Barakat recommends that all women with breast cancer, with or without tamoxifen, should undergo an annual gynecologic evaluation. Unfortunately, this recommendation is in contrast with earlier statements, is confusing, and may feed the anxiety of both doctors and patients. Besides, it remains unclear what should be done or looked for during these assessments. In our opinion, based on presently available data and affirmed by the study of Love et al, the recommendation should be that tamoxifen-treated patients should be instructed and encouraged to report abnormal vaginal discharge or bleeding. Only those who present with symptoms should have a hysteroscopy with endometrial sampling, to exclude or diagnose endometrial cancer. REFERENCES
1.
Love CDB, Muir BB, Scrimgeour JB, et al: Investigation of endometrial abnormalities in asymptomatic women treated with tamoxifen and an evaluation of the role of endometrial cancer screening. J Clin Oncol 17:2050-2054, 1999
2.
Barakat RR: Screening for endometrial cancer in the patient receiving tamoxifen for breast cancer. J Clin Oncol 17:1967-1968, 1999 3. Goldstein SR: Unusual ultrasonographic appearance of the uterus in patients receiving tamoxifen. Am J Obstet Gynecol 170:447-451, 1994[Medline] 4. Mourits MJ, van der Zee AG, Willemse PH, et al: Discrepancy between ultrasonography and hysteroscopy and histology of endometrium in postmenopausal breast cancer patients using tamoxifen. Gynecol Oncol 73:21-26, 1999[Medline]
5.
Decensi A, Fontana V, Bruno S, et al: Effect of tamoxifen on endometrial proliferation. J Clin Oncol 14:434-440, 1996
ResponseEdinburgh Breast Unit Western General Hospital Edinburgh, United Kingdom Reply 1:Mourits et al indicate that based on a study of 53 patients, but with histology results from only three who underwent hysterectomy while on tamoxifen, the thickened endometrium seen in patients on TVU is due to cystically dilated glands and dense endometrial stroma. They conclude that the thickened endometrium in women with normal hysteroscopy results correlates with histologic changes within the endometrium rather than in the subendometrial or myometrial layers. We have also been interested in the histologic changes in the endometrium of women on tamoxifen and have been frustrated by our inability to satisfactorily biopsy endometrium of study patients. Therefore, we identified 134 women in the last 2 years by data linkage from the Information and Statistics Department, Trinity Park House, Edinburgh, who had a diagnosis of breast cancer and had undergone hysterectomy. Thirty-four hysterectomy specimens from women who were taking tamoxifen at the time of hysterectomy and 14 control specimens from women with a diagnosis of breast cancer who had never received tamoxifen were retrieved and assessed. All hysterectomies were performed for noncancer causes. To our knowledge, this is the first study to compare the histologic characteristics of tamoxifen-treated patients with those of an appropriate series of control patients. There were three statistically significant differences between the endometrium of tamoxifen users and controls; tamoxifen-exposed endometrium was more likely to show cystic dilation of endometrial glands, low stromal cellularity, and prominence of collagen within the stroma. This larger series confirms some of the observations of Mourits et al and indicates that the sonographic changes correlate directly with histologic changes in the endometrium. In the Edinburgh Breast Unit, a regional breast cancer unit dealing with 700 new patients diagnosed with breast cancer per year, on the basis of the results of our study and of other studies in the literature, women on tamoxifen do not undergo endometrial screening or have regular gynecologic examinations. Women are encouraged to report any abnormal bleeding or discharge promptly so that they may be appropriately investigated. This policy is consistent with the view expressed by Mourits et al that endometrial screening is not worthwhile.
ResponseMemorial Sloan-Kettering Cancer Center New York, NY Reply 2:In response to Mourits et al’s letter regarding tamoxifen and endometrial screening, it would seem that we are in agreement that there is no benefit to routinely screening the endometrium in a tamoxifen-treated patient. I also agree that tamoxifen-treated patients should be instructed and encouraged to report abnormal vaginal discharge or bleeding and that endometrial sampling should be reserved to these patients. Mourits et al state that they are confused with our recommendation, however, that all women with breast cancer, whether or not they are receiving tamoxifen, should undergo annual gynecologic evaluation. In the United States, in many cases, the gynecologist serves as the primary care physician, which provides an opportunity for women to have their general physical condition evaluated and undergo comprehensive examination, including monitoring of their blood pressure and weight as well as an evaluation of other organ systems. In no way does this statement imply that annual gynecologic evaluation should include any form of endometrial sampling in asymptomatic breast cancer patients whether or not they are taking tamoxifen. I disagree with Mourits et al’s statement that the routine gynecologic evaluation may feed the anxiety of both doctors and patients. On the contrary, an annual examination may provide the patient with reassurance and a sense of well-being.
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Copyright © 2000 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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