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Side Effects of Therapy

CASE 2. Tamoxifen and Uterine Abnormalities

Department of Medical Oncology, Department of Gynecologic Oncology, Department of Pathology, University Hospital of Groningen, the Netherlands

A 58-year-old postmenopausal woman was treated by a modified radical mastectomy for an estrogen and progesterone receptor–positive T1/N0/M0 grade 2 ductal left breast cancer. She received adjuvant tamoxifen 20 mg daily. At the age of 60 years, she was referred with a 15-month history of vaginal bleeding, and a large pelvic mass.

At gynecologic examination, a central pelvic mass was present. Transvaginal ultrasound (TVU) revealed an enlarged uterus with markedly increased endometrial thickness of 7 to 8 cm, with a multicystic appearance. The ovaries seemed to be normal without ascites. Saline infusion sonography showed a large intrauterine polyp, as well as the multicystic pattern (Fig 1, arrow). Hysteroscopy indicated that this large polyp had a smooth surface (Fig 2). A biopsy of the polyp showed cystically dilated glands lined with flattened epithelium surrounded by dense, condensed stroma. The surface of the polyp was also lined with unilayered, atrophic epithelium (Fig 3). Because of persistent bleeding, a total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed (Fig 4).

View larger version (143K): [in this window] [in a new window]   Fig 1.

View larger version (112K): [in this window] [in a new window]   Fig 2.

View larger version (173K): [in this window] [in a new window]   Fig 3.

View larger version (114K): [in this window] [in a new window]   Fig 4.

TVU is a noninvasive method of screening for endometrial cancer; however, in postmenopausal tamoxifen-treated women, TVU can give confounding ultrasound images.³ In as many as 90% of postmenopausal tamoxifen users, TVU shows an increased irregular endometrial thickness suggestive of endometrial pathology.^3,4 These tamoxifen-induced sonographic findings, resembling Swiss cheese, are explained by the dense stroma and fluid-filled, dilated endometrial glands causing echolucent areas on ultrasound, which are mainly responsible for the enhanced endometrial thickness.³ Due to the high false-positive rate of TVU screening and the low incidence of malignancy, TVU screening in asymptomatic tamoxifen users is considered to be unwarranted,⁵ though there still is controversy on this issue.

Tamoxifen-treated patients should be instructed and encouraged to report abnormal vaginal bleeding. Those who present with symptoms should have a hysteroscopy with endometrial sampling to exclude endometrial cancer or sarcoma, irrespective of the ultrasound findings. Physicians should be aware of the confounding effects of tamoxifen on the histological and ultrasonographic appearance of the endometrium. A multicystic endometrium or benign polyps, such as found in our patient, are typical for chronic tamoxifen users, and may confuse the unaware.

Authors' Disclosures of Potential Conflicts of Interest

The authors indicated no potential conflicts of interest.

REFERENCES

1. Bergman L, Beelen ML, Gallee MP: Risk and prognosis of endometrial cancer after tamoxifen for breast cancer: Comprehensive Cancer Centres' ALERT Group—Assessment of Liver and Endometrial Cancer Risk Following Tamoxifen. Lancet 356:881–887, 2000[CrossRef][Medline]

2. Bernstein L, Deapen D, Cerhan JR, et al: Tamoxifen therapy for breast cancer and endometrial cancer risk. J Natl Cancer Inst 91:1654–1662, 1999[Abstract/Free Full Text]

3. 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[CrossRef][Medline]

4. Cohen I, Rosen DJ, Tepper R, et al: Ultrasonographic evaluation of the endometrium and correlation with endometrial sampling in postmenopausal patients treated with tamoxifen. J Ultrasound Med 12:275–280, 1993[Abstract]

5. Love CD, Muir BB, Scrimgeour JB, et al: Investigation of endometrial abnormalities in asymptomatic women treated with tamoxifen and an evaluation of the role of endometrial screening. J Clin Oncol 17:2050–2054, 1999[Abstract/Free Full Text]

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