The effect of tamoxifen on the endometrium _ cancer network

The indications for tamoxifen use have broadened to include long-term adjuvant therapy as well as preventive therapy for selected high-risk women. Biopsy endometrial Consequently, a large number of women, including healthy young patients with no history of cancer, will be subjected to the long-term effects of tamoxifen. Skin biopsy results time This review evaluates the current literature regarding tamoxifen use in breast cancer patients and associated uterine neoplasia, and discusses the role of screening for endometrial cancer in tamoxifen-treated breast cancer patients.


Several preclinical studies have indicated that tamoxifen may indeed exert an estrogenic effect on the endometrium. Pipelle endometrial biopsy Satyaswaroop et al [14] transplanted both ER-positive and ER-negative human endometrial cancer cell lines into nude mice and evaluated the effect of both tamoxifen and 17-beta-estradiol on tumor growth. Endometrial biopsy procedure Although the ER-negative tumor grew rapidly, there was no difference in the rate of tumor growth between tamoxifen- and estrogen-treated animals, compared with controls. Endometrial biopsy side effects In contrast, the rate of growth of the ER-positive cell line was significantly accelerated in the tamoxifen-treated animals, compared with controls, although to a lesser degree than was seen with estrogen treatment. Liver biopsy recovery time In addition, tamoxifen increased the levels of functional progesterone receptors, providing further evidence for the estrogenic potential of tamoxifen.

Gottardis et al [15] demonstrated in athymic mice the contrasting actions of tamoxifen on the growth of ER-positive breast and endometrial cancer cell lines. Abnormal endometrial biopsy results While stimulating the growth of the endometrial tumor, tamoxifen had no effect on breast tumor growth and had an antagonistic action on the estradiol-stimulated growth of breast tumors.

The estrogenic effect of tamoxifen on the female genital tract has also been demonstrated clinically. Endometrial biopsy recovery Boccardo et al [16] investigated the estrogen-like effect of tamoxifen on the vaginal epithelium. Endometrial biopsy video Hormonal evaluation of the female patient can be determined by means of exfoliative vaginal cytology using the karyopyknotic index (KPI), which is the relation of mature superficial cells to intermediate cells. Pain after endometrial biopsy Postmenopausal estrogen replacement therapy generally induces increased cellular maturity and, consequently, increases the KPI. Cervical biopsy recovery After at least 8 weeks of tamoxifen treatment, treated patients had a significantly higher KPI than did untreated patients, suggesting an estrogenic effect of tamoxifen on the vaginal epithelium.

Several recent reports have implicated tamoxifen treatment in the development of endometrial polyps and hyperplasia ( Table 1 ). Endometrial biopsy complications Lahti et al [9] performed transvaginal sonography, hysteroscopy, and endometrial curettage on 103 postmenopausal breast cancer patients; 51 had received tamoxifen at 20 to 40 mg/day for a median of 30 months, while 52 had received no hormonal treatment. Hysteroscopy endometrial biopsy The patients were matched with respect to age, parity, time since menopause, body mass index, and concomitant medical conditions. Breast biopsy recovery time Compared with control subjects, the tamoxifen-treated patients had a significantly thicker mean endometrial width (10.4 mm versus 4.2 mm) and a larger uterine volume, as determined by transvaginal sonography. Endometrial biopsy ivf However, they also had a higher incidence of uterine fibroids.

The percentage of endometrial polyps was significantly higher in the tamoxifen-treated group, compared with controls (36% vs 10%). Endometrial biopsy pain Of the 43 patients in the tamoxifen-treated group who had an endometrial thickness of 5 mm or more, 17 (39.5%) had endometrial polyps; however, 22 (51.2%) had no abnormal pathologic findings. Breast biopsy recovery Two patients in the tamoxifen group had endometrial hyperplasia, and one patient had endometrial cancer at the time of curettage. Endometrial biopsy results time frame Two patients in the control group also had endometrial cancer. Endometrial biopsy results interpretation All significant endometrial pathology was found in asymptomatic patients with an endometrial width greater than 5 mm on transvaginal sonography. Endometrial biopsy results If transvaginal sonography were used as a screening method for endometrial cancer with the abnormal cutoff limit set at 5 mm, approximately 50% of patients would undergo endometrial sampling unnecessarily.

Since endometrial polyps often contain hyperplastic endometrial glands, their etiology is thought to be the presence of endogenous or exogenous estrogenic activity. Bleeding after endometrial biopsy The authors therefore concluded that long-term tamoxifen use is associated with estrogenic side effects manifested by an increased occurrence of polyps. What is endometrial biopsy This study failed to demonstrate any increase in precancerous or cancerous endometrial lesions associated with tamoxifen treatment.

Other Studies—Other authors have also reported a higher incidence of endometrial polyps and hyperplasia in tamoxifen-treated breast cancer patients. Endometrial biopsy results how long Corley et al [17] reported on four tamoxifen-treated patients who developed unusual endometrial polyps characterized by cystically dilated glands and stromal decidualization. What is an endometrial biopsy These findings were not confirmed in the 17 cases of endometrial polyps reported by Lahti et al [9].

Gal et al [18] reported an 18% incidence of endometrial hyperplasia in random endometrial biopsies obtained from 38 breast cancer patients who had received tamoxifen at a dosage of 20 mg/day for at least 12 months. Biopsy endometrial Thirty-two patients (46%) who were initially eligible for study could not participate, as endometrial samples could not be obtained due to atrophic changes. Skin biopsy results time In the second phase of the study, the authors performed endometrial biopsies prospectively on 11 patients at 4- to 6-month intervals. Pipelle endometrial biopsy Three (28%) of these patients developed endometrial hyperplasia following 6, 10, and 12 months of tamoxifen use. Endometrial biopsy procedure Again, 40% of the patients initially eligible for study could not participate due to inability to undergo an endometrial biopsy. Endometrial biopsy side effects The 20% overall incidence of endometrial hyperplasia reported by Gal et al [18] was higher than the 4% incidence noted by Lahti et al [9] in 51 tamoxifen-treated breast cancer patients.

Gibson et al [19] recently reported the results of a retrospective review of endometrial pathology found at dilatation and curettage (D&C) performed in 240 breast cancer patients. Liver biopsy recovery time Seventy-five (31%) of these patients had received tamoxifen, 20 mg/day, for a mean duration of 26 months as therapy for their breast cancer. Abnormal endometrial biopsy results Patients in this study were stratified as symptomatic (abnormal bleeding) or asymptomatic (curettage performed as part of another procedure or due to the presence of a thickened endometrial stripe on ultrasound examination).

Among tamoxifen users who were symptomatic at the time of D&C, the incidence of endometrial polyps was 15%; hyperplasia, 2%; and adenocarcinoma, 11%; compared with an incidence of 13%, 4%, and 11%, respectively, for nonusers. Endometrial biopsy recovery Among asympto- matic patients receiving tamoxifen, the incidence of polyps, hyperplasia, and adenocarcinoma was 9%, 0%, and 0%, while nonusers had an incidence of 5%, 4%, and 0%, respectively. Endometrial biopsy video All of the cases of endometrial carcinoma were associated with abnormal vaginal bleeding. Pain after endometrial biopsy The 11% incidence of endometrial carcinoma in this study was comparable to what has been reported for all patients presenting with postmenopausal bleeding in the general population [20].

The mean duration of tamoxifen use in those patients found to have adenocarcinoma was 44 months, compared with 18 months in those patients with polyps, and 19 months in the patient with hyperplasia. Cervical biopsy recovery This difference was not statistically significant, possibly due to small numbers. Endometrial biopsy complications The authors concluded that short-term tamoxifen use at the 20 mg/day dosage level was not associated with a higher incidence of abnormal pathology, as detected at the time of D&C in breast cancer patients.

Breast Cancer Prevention Trials—Recently, large-scale randomized trials of tamoxifen as a chemopreventive agent have been initiated in England and the United States for women considered to be at high risk for developing breast cancer based on family history. Hysteroscopy endometrial biopsy Kedar et al [21] recruited a randomized cohort of 111 postmenopausal women from the Pilot Breast Cancer Prevention Trial at the Royal Marsden Hospital, to study the effect of tamoxifen on the uterus and ovaries. Breast biopsy recovery time Sixty-one patients had received tamoxifen at 20 mg/day for a median of 22 months, while 50 had received placebo for a median of 24 months. Endometrial biopsy ivf Eight patients in each group were receiving estrogen replacement therapy at the time of study.

All patients underwent endovaginal sonography with color Doppler imaging, after which an endometrial biopsy was performed. Endometrial biopsy pain The tamoxifen group was found to have a significantly larger uterine volume and a lower impedance to blood flow in the uterine arteries. Breast biopsy recovery Patients were not, however, stratified as to the presence of uterine fibroids. Endometrial biopsy results time frame In addition, the tamoxifen-treated group had a significantly thicker mean endometrial diameter (9.1 mm versus 4.8 mm). Endometrial biopsy results interpretation On endometrial biopsy, 10 patients (16%) in the tamoxifen-treated group were found to have atypical endometrial hyperplasia, while five (8%) had endometrial polyps. Endometrial biopsy results None of the patients in the control group had hyperplasia on endometrial biopsy, and only one patient had an endometrial polyp. Bleeding after endometrial biopsy No patient in either group had evidence of endometrial carcinoma. What is endometrial biopsy The predictive value of an endometrial thickness 8 mm or larger for atypical hyperplasia or polyps was 100% (16/16), suggesting a possible screening role for transvaginal sonography in breast cancer patients receiving tamoxifen.