Reproductive tract pathology in asymptomatic women treated with tamoxifen

Purpose: To determine the long-term effects of tamoxifen on the female reproductive tract in patients with breast cancer.

Methods: Forty-nine patients with breast cancer receiving tamoxifen longer than two years were analyzed. All the patients underwent pelvic examination, pap smear, transvaginal ultrasonography, serum CA 125 and dilatation and curettage.

Results: There were 16 patients with genital system pathology. Three of them had atypical Pap smears, one with cervical carcinoma and the other two with chronic cervicitis. Two significant ovarian pathologies were found. These were ovarian fibroma, and unilateral dermoid cyst. There were three patients with endometrial hyperplasia without atypia. Uterine myoma was encountered in seven of the cases. Only one patient had elevated CA 125 levels despite normal genital examination findings.

Conclusion: Since no significant genital pathology attributable to tamoxifen therapy could be detected, the follow-up for gynecologic pathologies in breast cancer patients receiving tamoxifen therapy may be individualized.

Tamoxifen; Breast cancer; Endometrial hyperplasia

[1] Sutherland M. C., Osborne C. K.: "Tamoxifen in premenopausal patients with metastatic breast cancer: a review". J. Clin. Oneal., 1991, 9, 1283.

[2] Goldhirsch A., Gelber R. D., Castiglione M.: "International Breast Cancer Study Group. Adjuvant therapy of breast cancer". Eur. J. Cancer, 1991, 27, 399.

[3] Ziegler L. D., Buzdar A. U.: " Current status of adjuvant therapy of early breast cancer". Am. J. Clin. Oneal., 1991, 14, 101.

[4] Buchanan R. B., Blarney R. W., Durrent K. R. et al.: "A randomized comparison of tamoxifen with surgical oophorectomy in premenopausal patients with advanced breast cancer". J. Clin. Oneal., 1986, 4, 1326.

[5] Early Breast Cancer Trialists'Collaborative Group: "Systemic treatment of early breast cancer by hormonal, cytotoxic, or immune therapy: 133 randomised trials involving 31,000 recurrences and 24,000 deaths among 75,000 women". Lancet, 1992, 339 (1), 71.

[6] Spinelli G., Bardozzi N., Citemessi A., Fontonarosa M., Curiel P.: "Endometrial carcinoma in tamoxifen treated cancer patients". J. Chemother., 1991, 3, 267.

[7] Nuovo M.A., Nuovo G. Y., McCaffrey R. M., Levi R. U., Barron B., Winkler B.: "Endometrial polyps in postmenopausal patients receiving tamoxifen". Jnt. J. Gynecol. Pathol., 1983, 8, 125.

[8] Cross S. S., Ismail S.: "Endometrial hyperplasia in an oophorectomized woman receiving tamoxifen therapy. Case report". Br. J. Obstet. Gynecol., 1990, 97, 551.

[9] Corly D., Rowe J., Curtis M. T., Hogon W. N., Noumoff J. S., Livolsi W. A.: "Postmenopausal bleeding from unusual endometrial polyps in women on chronic tamoxifen therapy". Obstet. Gynecol., 1992, 79, 111.

[10] Gusberg S. B.: "Tamoxifen for breast cancer: associated endometrial cancer". Cancer, 1990, 65, 1463.

[11] Clark J. H., Anderson J. N., Peck S.: "Estrogen receptor-antiestrogen complex: Atypical binding by uterine nuclei and effects on uterine growth". Steroids, 1973, 22, 707.

[12] Ferrazi E., Cartei G., Mattarazoa R., Fiorentino M.: "Oestrogenlike effect of tamoxifen on vaginal epithelium". Br. Med. J., 1977, 1, 1351.

[13] Boccardo F., Bruzzi P., Rubagotti A., Nocolo G., Rosso R.: "Estrogen- like action of tamoxifen vaginal epithelium in breast cancer patients". Oncology, 1981, 38, 281.

[14] Boccardo F., Guarnieri D., Rubagotti A., Casterelli G. L., Bentiroglio G. et al.: "Endocrine effects of tamoxifen in postmenopausal breast cancer patients". Tumor, 1984, 70, 61.

[15] Rayter Z., Gazet J. C., Shepherd J., Trott P.A., Fisher C., Svenson W. E., Ford H. T., Hern R. A.: " Gynecological cytology and pelvicultrasonography in patients with breast cancer taking tamoxifen compared with controls". Eur. J. Surg. Oneal., 1994, 20, 134.

[16] Manni A., Pearson 0. H.: "Antiestrogen-induced remissions in premenopausal women with stage IV breast cancer: Effects on ovarian function". Cancer Treat. Rep., 1980, 64, 779.

[17] Rose D. P., Davis T. E.: "Effects of adjuvant chemohormonal therapy on the ovarian and adrenal function of breast cancer patients". Cancer Res., 1980, 40, 4043.

[18] Sherman B. M., Chapler F. K., Crickard K., Wycoff D.: "Endocnne consequences of continuous antestrogen therapy with tamoxifen in premenopausal women". J. Clin. Invest., 1979, 64, 398.

[19] Lahti E., Blanco G., Kauppila A., Sarkkinen M.A., Taskinen P., Laatikainen T.: "Endometrial changes in postmenopausal breast cancer patients receiving tamoxifen". Obstet. Gynecol., 1993, 81, 660.

[20] Breast Cancer Trials Committee, Scottish Cancer Trials Office(MRC), Edinburgh: "Adjuvant tamoxifen in the management of operable breast cancer: The Scottish Trial". Lancet, 1987, ii, 171.

[21] Malfetano J. H.: "Tamoxifen-associated endometrial carcinoma in postmenopausal breast cancer patients". Gynecol. Oncol., 1990, 39, 82.

[22] Fornander T., Cedermark B., Mattsson A. et al.: "Adjuvant tamoxifen in the management in early breast cancer: Occurrence of new primary cancer". Lancet, 1989, i, 117.

[23] Anderson M., Storm H. H., Mouridsen H. T.: "Incidence of new primary cancers after adjuvant therapy and radiotherapy for early breast cancer". J. Natl. Cancer Inst., 1991, 83, 1013.

[24] Ozsener S., Ozaran A., ltil I., Dikmen Y.: "Endometrial pathology of 104 postmenopausal breast cancer patients treated with tamoxifen". Eur. J. Gynaecol. Oncol., 1998, 19 (6), 580.

[25] Treilleux T., Mignotte H., Clement-Chassagne C., Guastalla P., Bailly C.: "Tamoxifen and malignant epithelial-nonepithelial tumours of the endometrium: report of six cases and review of the literature". Eur. J. Surg. Oncol., 1999, 25 (5), 477.

[26] Bernstein L., Deapen D., Cerhan J. R., Schwartz S. M., Liff L., McGann-Maloney E. et al.: "Tamoxifen therapy for breast cancer and endometrial cancer risk". J. Natl. Cancer Inst., 1999, 6, 91(19), 1654.

[27] Love C. D., Muir B. B., Scrimgeour J.B., Leonard R. C., Dillon P., Dixon J. M.: "Investigation of endometrial abnormalities in asymptomatic women treated with tamoxifen and an evaluation of the role of endometrial screening". J. Clin. Oncol., 1999, 17 (7), 2050.