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Tamoxifen and endometrial cancer. Is screening necessary? A review of the literature

  • F. Machado1,*,
  • J.R. Rodriguez1
  • J.P.H. Leon2
  • J.R. Rodriguez1
  • J.J. Parrilla1
  • L. Abad1

1Gynaecology and Obstetrics Service, Hospital Virgen de la Arrixaca, Spain

2Oncological Pharmacy Unit. Hospital Morales Meseguer,. Murcia, Spain

DOI: 10.12892/ejgo200503257 Vol.26,Issue 3,May 2005 pp.257-265

Published: 10 May 2005

*Corresponding Author(s): F. Machado E-mail:

Abstract

Tamoxifen is a selective oestrogen receptor modulator (SERM) with anti-oestrogenic activity in the breast and oestrogenic effects in various tissues such as the endometrium, bone and cardiovascular territory. As adjuvant hormone therapy, it has a clear beneficial effect in patients with breast cancer, reducing relapses, contralateral breast cancer and mortality. Its most important secondary effect is a greater rate of occurrence of endometrial cancer. Although the risk/benefit ratio is clearly positive, the follow-up on these patients is still an issue. In women with metrorrhagia, it is clear that an endometrial sample must be obtained for histological examination and the best procedure today is hysteroscopic-directed biopsy. Nevertheless, the need to screen asymptomatic patients is not universally accepted. The vaginal ultrasound scan gives a great number of false positives. This entails more aggressive and more expensive procedures such as hysteroscopic-directed biopsy, meaning greater expense and more complications. As a result, the cost/benefit ratio is not very favourable. The rate of occurrence of endometrial cancer in 1026 tamoxifen-treated patients with breast cancer in our hospital between 1999 and 2001 was 1.25%. Two cases were diagnosed in asymptomatic patients. In this article, we analyse the literature on the need to screen patients on tamoxifen and about the most appropriate diagnostic protocol.

Keywords

Tamoxifen; Endometrial cancer; Endometrial effects; Screening

Cite and Share

F. Machado,J.R. Rodriguez,J.P.H. Leon,J.R. Rodriguez,J.J. Parrilla,L. Abad. Tamoxifen and endometrial cancer. Is screening necessary? A review of the literature. European Journal of Gynaecological Oncology. 2005. 26(3);257-265.

References

[1] Beatson G.T.: "On the treatment of inoperable cases of the mamma: suggestions for new method of treatment with illustrative cases". Lancet, 1986, 2, 104.

[2] Schizinger A.: "Uber carcinoma mammae". Verh. Dtsch Ges. Chir, 1889, 18, 28.

[3] Cole M.P., Jones C.T.A., Todd l.D.H.: "A new antiestrogenic agent in late breast cancer: An early clinical appraisal of ICI 46,474". Br. J. Cancer, 1971, 25, 270.

[4] Neven P., Vernaeve H.: "Guidelines for monitoring patients taking tamoxifen treatment". Drug. Safety, 2000, 22.

[5] Powles T.J.: "Efficacy of Tamoxifen as treatment of breast cancer". Semin. Oneal., 1997, 24 (suppl. 1), 48.

[6] Forbes J.P.: "The control of breast cancer: the role of tamoxifen". Semin. Oncol., 1997, 24 (suppl. I), 5.

[7] Fisher B., Constantino J.P., Wickerman D.L., Redmon C.K., Kavanah M., Cronin W.M. et al.: "Tamoxifen for the preventionof breast cancer Report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study". J. Natl. Cancer Inst., 1998, 90, 1371.

[8] Ault A.: "Tamoxifen prevention claim will not be allowed in the USA". Lancet, 1998, 352, 883.

[9] Speroff L., Glass R.H., Kase G.K.: "Biosfntesis, metabolismo y mecanismo de acci6n de las hormonas (capt. 2)". Endocrinologia Ginecol6gica e Infertilidad (I" edition in Spanish).

[10] Sutherland R.L., Green M.D., Hall R.E., Reddel R.R., Taylor l.W: "Tamoxifen induces accumulation of MCF-7 human mammary carcinoma cells in GO/GI phase of the cell cycle". Eur. J. Clin. Oneal., 1983, 19, 615.

[11] Gustall J.P., Catimel G., Blay J.Y. et al.: "Tratamiento del cancer de mama no metastatico: formas hahituales". Enciclopedia Medico-Quirurgica, 871-A-10.

[12] Murphy L.C.: "Antiestrogen action and growth factor regulation". Breast Cancer Res. Treat., 1994, 31, 61.

[13] Neven P., Vergote I.: "Tamoxifen, screening and new oestrogen receptor modulators". Best Prac. Res. Clin. Obstet. Gynaecol., 2001, 15, 365.

[14] Fisher B., Dignam J., Bryan J. et al.: "Five versus more than five years of tamoxifen therapy for breast cancer patients with negative lymph nodes and estrogen receptor-positive tumours". J. Natl. Cancer Inst., 1996, 88, 1529.

[15] Sterwart H.J., Forrest A.P., Everington D. et al.: "Randomized comparison of 5 years of adjuvant tamoxifen with continuous therapy for operable breast cancer". Br. J Cancer, 1996, 74, 297.

[16] Horwitz K.B.: "Hormone-resistant breast cancer or'feeding the hand that bites you'". Prag. Clin. Biol. Res., 1994, 387, 29.

[17] Killackey M.A., Hakes T.B., Pierce V.K.: "Endometrial adenocarcinoma in breast cancer patients receiving antiestrogens". Cancer Treat. Rep., 1985, 69, 237.

[18] Rutqvist L.E., Johanson H., Signomklao T., Johansson U., Fornander T., Wilking N.: "Adjuvant tamoxifen therapy for early stage breast cancer and second primary malignancies". J. Natl. Cancer Inst., 1995, 87, 645.

[19] Fisher B., Constantino J.P., Redmond C.K., Fisher E.R., Wickerham D.L., Cronin W.M.: "Endometrial cancer in tamoxifen treated breast cancer patients: Findings from the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-14". J. Natl. Cancer Inst., 1994, 86, 527.

[20] Curtis R.E., Boice J.D., Shriner D.A., Hnakey B.F., Fraumeni J.P.: "Second cancers after adjuvant therapy for breast cancer". J. Natl. Cancer Inst., 1996, 88, 332.

[21] Early Breast Cancer Trialists'Collaborative Group: "Tamoxifeno para el cancer de mama precoz. En: La Cochrane Library plus en espafiol Oxford: Update Software".

[22] Speroff L., Glass R.H., Kase G.K.: "Las mamas (capt. 16)". Endocrinologia Ginecol6gica e lnfertilidad (I" edition in Spanish).

[23] Mourits M.J.E., De V ries E., Willense P., Ten Hoor K., Hollema H., Van der Zee A.:'Tamoxifen treatment and gynecologic side effects: A review". Obstet. Gynaecol., 2001, 97, 5.

[24] Berstein L., Deapen D., Cerhan J.R., Swartz S., Liff J., McGann-Maloney E., Pearlman J.A., Ford L.: "Tamoxifen therapy for breast cancer and endometrial cancer risk". J. Natl. Cancer Inst., 1999, 91, 1654.

[25] Powles T.J., Bourne T., Athanasious S. et al.: "The effects of norethisterone on endometrial abnormalities identified by transvaginal ultrasound screening of healthy postmenopausal woman on tamoxifen or placebo". Br. J. Cancer, 1998, 78, 272.

[26] Gardner F.J.E., Konje J.C., Abrams K.R. et al.: "Endometrial protection from tamoxifen stimulated changes by a levonorgestrel releasmg intrauterine system: a randomized controlled trial". Lancet, 2000, 356, 1711.

[27] Magriples U., Boice J.D., Shriner D.A., Hankey B.F., Fraumeni J.P. et al.: "High-grade endometrial carcinoma in tamoxifen-treated breast cancer patients". J. Clin. Oneal., 1993.

[28] Barakat R.R., Wong G., Curtin J.P. et al.: "Tamoxifen use in breast-cancer patients who subsequently develop corpus cancer is not associated with a higher incidence of adverse histological features". Gynecol. Oneal., 1994, 55, 164.

[29] Bergman L., Beelen M.L.R., Gelmann E.P.: "Risk and prognosis of endometrial cancer after tamoxifen for breast cancer". Lancet, 2000, 356, 881.

[30] Wickerham D.L., Fisher B., Wolmark N. et al.: "Association of tamoxifen and uterine sarcoma". J. Clin Oneal., 2002, 20, 2758.

[31] O'Regan R., Craig J.: "Tamoxifen and raloxifene and beyond". Semin. Oneal., 2001, 28, 260.

[32] Neven P., De Muylder X., Van Belle Y., Van Hoof V., Vanderick G.: "Longintudinal hysteroscopic follow-up during tamoxifen treatment" Lancet, 1998, 351, 36.

[33] Ascher S.M., Imakoa I., Lage J.M.:'Tamoxifen-induced uterine abnormalities: The role of imaging". Radiology, 2000, 214, 29.

[34] Ismail S.M.: "Pathology of endometrium treated with tamoxifen". J. Clin. Pathol., 1994, 47, 827.

[35] McGonigle K.F., Swaw S.L., Vasilev S.A., Odom-Maryon T., Roy S., Simpson J.P.: "Abnormalities detected on transvaginal ultrasonography in tamoxifen-treated postmenopausal breast cancer patients may represent endometrial cystic atrophy". Am. J. Obstet. Gynecol.. 1998, 178, 1145.

[36] Goldstein S.R.: "Unusual ultrasonic appearance of the uterus in patients receiving tarnoxifen". Am. J. Obstet. Gynecol.,1994, 170, 447.

[37] Vosse M., Renard F., Coibion M., Neven P., Nogaret J.M., Hertens D.: "Endornetrial disorders in 406 breast cancer patients on tarnoxifen: the case for less intensive monitoring". Eur. J. Obstet. Gynecol. Rep rod. Biol., 2002, 101, 58.

[38] Neven P., De Muylder X., Van Belle Y., Vanderick G., De Muylder E.: "Tamoxifen and the uterus and endometriurn". Lancet, 1989, 2, 375.

[39] Lahti E., Blanco G., Kauppila A., Apaja-Sarkiknen M., Taskinen P.J., Laatiniken T.: "Endornetrial changes in postrnenopausal breast cancer patients receiving tamoxifen". Obstet. Gynecol., 1993, 81, 660.

[40] Cohen I.,A zaria R.,B erheim J., Enhapira J.,B eyth T.: "Risk factors of endometrial polyps resected from postmenopausal patients with breast carcinoma treated with tamoxifen". Cancer, 2001, 92, 1151.

[41] Biron-Shental T., Tepper R., Fishman A., Shapira J., Cohen I.: "Recurrent endometrial polyps in postmenopausal breast cancer patients on tamoxifen". Gynecol. Oncol., 2003, 90, 382.

[42] Cohen I.,B ernheim J.,A zaria R.,T epper R.,S harony R.,B eyth Y.: "Malignant endometrial polyps in postmenopausal breast cancer tamoxifentreated patients". Gynecol. Oncol., 1999, 75, 136.

[43] McCluggage W.G., Sumathi M., McManus M.: "Uterine serous carcinoma and endometrial intraepithelial carcinoma arising in endornetrial polyps, report of 5 cases, including 2 associated with tamoxifen therapy". Hum. Pathol., 2003, 34, 939.

[44] Berliere M., Galant C., Donnez J.: "The potential oncogenic effect of tamoxifen on the endometrium". Human Reprod.,1999, 14, 1381.

[45] Varras M.,P olyzos D.,A krivis Ch.: "Effects of tamoxifen on the female's genital tract: review of the literature". Eur. J. Gynaecol. Oncol., 2003, 24, 3.

[46] Kedar R.P., Bourne T.H., Powles T.J. et al.: "Effects of tamoxifen on uterus and ovaries of postmenopausal women in a randomised breast cancer prevention trial". Lancet, 1994, 343, 1318.

[47] Klopper A., Hall M.: "New synthetic agent for the induction of ovulation. Preliminary trial in women". Br. J. Med., 1971, 2, 152.

[48] Kazandi M., Sendag F., Terk M., Ozsaran A., Dikmen Y.: Eur. J. Gynaecol. Oneal., 2002, 23, 257.

[49] Chang J., Powles T.J., Ashley S.E., Iveson T., Gregory R.K., Dowsett M.: "Variation in endometrial thickening in women with amenorrhea on tamoxifen". Breast Cancer Res. Treat., 1998, 48, 81.

[50] Love R.R.,N ewcomb P.A. et al.: "Effects of tamoxifen therapy on lipid and lipoprotein levels in postmenopausal patients with node-negative breast cancer". J. Natl. Cancer Inst., 1990, 82, 3191.

[51] Elisaf M.S.,N akou K.,L iamis G.,P aulidis N.A.: "Tamoxifen-induced severe hypertriglyceridemia and pancreatitis". Ann. Oncol., 2000, 11, 1067.

[52] Love R.R., Mazes R.B., Barden H.S. et al.: "Effects of tamoxifen on bone mineral density in postmenopausal women with breast cancer". N Engl. J. Med., 1992, 326, 852.

[53] Lazzaroni F., Scorolli L. et al.: "Tamoxifen retinopathy: does it really exist?". Graesfes Arch. Clin. Exp. Opththalmol., 1998, 236, 669.

[54] Brown K.: "Breast cancer chemoprevention: risk-benefit effects of the anti-oestrogen tamoxifen". Expert. Opin. Drug Sqf., 2002, 1, 253.

[55] Braithwaite R.S., Rowan T. et al.: "Meta-analysis of vascular and neoplasic events associated with tamoxifen". J. Gen. Intern. Med., 2003, 18, 937.

[56] Mourits M.J.E., Van der Zee A.G.J. et al.: "Discrepancy between ultrasonography and hysteroscopy and histology of endometrium in postmenopausal breast cancer patients using tamoxifen". Gynecol. Oncol., 1999, 73, 21.

[57] Rayter Z., Watt M., Keay S. et al.: "The effect of tamoxifen on endometrial thickness and endometrial histology". Eur. J. Cancer, 2000, 36, S98.

[58] McGonigle K.F., Marx H.F., Morgan R.J. et al.: "Uterine effects of tamoxifen: a prospective study". Gynecol. Oncol., 1999, 74, 324.

[59] Love C.D.B., Dixon J.M.: "Thickened endometrium caused by tamoxifen returns to normal following tamoxifen cessation". The Breast, 2000, 9, 156.

[60] Gerber B., Krause A., Millier H. et al.: "Effects of adjuvant tamoxifen on the endometriurn in postmenopausal women with breast cancer: A prospective long-term study using transvaginal ultrasound". J. Clin. Oncol., 2000, 18, 3464.

[61] Love C.D.P., Muir B.B. et al.: "Investigation of endometrial abnormalities in asymptomatic women treated with tamoxifen and an evaluation of the role of endometrial screening". J. Clin. Oncol., 1999, 17, 2050.

[62] Ciatto S., Cechini S., Gervasi G., Landini A., Zappa M., Crocetti E.: "Surveillance for endometrial cancer with transvaginal ultrasonography of breast cancer patients under tamoxifen treatment". Br. J. Cancer, 2003, 88, 1178.

[63] Renard F., Vosse M., Scagnol I., Verhest A.: "Aggressive endometrial carcinoma in a breast cancer patient treated with tamoxifen with normal transvaginal ultrasonography. Case report". Eur. J. Gynaecol. Oneal., 2002, 23

[64] Seoud M., Shamseddine A., Khalil A. et al.: "Tamoxifen and endometrial pathologies: A prospective study". Gynecol. Oncol., 1999, 75, 15.

[65] Love R.R.: "Tamoxifen prophylaxis in breast cancer". Oncol., 1992, 6, 33.

[66] Fung K., Fung M., Reid A. et al.: "Prospective longitudinal study of ultrasound screening for endometrial abnormalities in women with breast cancer receiving tarnoxifen". Gynecol. Oneal., 2003, 91, 154.

[67] Bourne T.H.,L awton F.,L eather A., Grandberg S.,C ambell S.,C ollins W.P.: "Use of intracavitary saline instillations and transvaginal sonography to detect tamoxifen associated endometrial polyps". Ultrasound Obstet. Gynecol., 1994, 4, 73.

[68] F ong K., Causer P. et al.: "Transvaginal US and hysterosonography in postmenopausal women with breast cancer receiving tamoxifeno: Correlation with hysteroscopy and pathology study". Radiographics, 2003, 23, 137.

[69] Tepper R., Beyth Y., Altaras M.M. et al.: "Value of sonohysterography in asymptomatic post menopausal tamoxifen-treated patients". Gynecol Oncol., 1997, 64, 386.

[70] Hann L., Cathleen M., Gonen M., Barakat R., Choi P., Bach A.: "Sonohysterography compared with endometrial biopsy for evaluation of the endornetrium in tamoxifen-treated women". J. Ultrasound Med., 2003, 22, 1173.

[71] Garuti G., Sambruni I. et al.: "Accuracy of hysteroscopy in predicting histopathology of endometrium in 1500 women". J. Am. Assoc. Gynecol. Laparosc., 2001, 8, 207.

[72] Oronzo C., Betochi S. et al.: "Comparison of hysteroscopic and hysterectomy findings to asses the diagnostic accuracy of office hysteroscopy in tamoxifen-treated patients with breast cancer". J. Am. Assoc. Gynecol. Laparosc., 2003, 10, 392.

[73] Cohen I., Azaria R. et al.: "Comparison of endometrial pathologies collected by hysteroscopy and hysterectomy in postrnenopausal breast cancer tamoxifen-treated patients". Eur. J. Gynecol. Oncol., 2000, 21, 418.

[74] Taponecco F., Curcio C. et al.: "Indication of hysteroscopy in tamoxifen treated breast cancer patients". J. Exp. Clin. Cancer Res., 2002, 21, 1.

[75] Machado F., Moreno J. et al.: "Accuracy of endometrial biopsy with the Cornier pipelle for diagnosis of endometrial cancer and atypical hyperplasia". Eur. J. Gynaec. Oneal., 2003, 24, 279.

[76] Shu-Bergman E.J., Goodman A.: "Surveillance for endometrial cancer in women receiving tamoxifen". Ann. Intern. Med., 1999, 131, 127.

[77] Barakat R.R., Gilewski T.A. et al.: "Effect of adjuvant tamoxifen on the endometrium in women with breast cancer: a prospective study using office endometrial biopsy". J. Clin. Oncol., 2000, 18, 3459.

[78] Labi FL., Meggirione M.P. et al.: "Cytological endometrial surveillance in tamoxifen-treated women". Eur. J. Gynaecol. Oneal., 2002, 23, 537.

[79] Aleem F., Predanic M. et al.: "Trans vaginal color and pulsed Doppler sonography of the endometrium: a possible role in reducing the number of dilatation and curettage procedures". J. Ultrasound Med., 1995, 14, 139.

[80] Achiron R., Lipitz S., Sivan E. et al.: "Changes mimicking endometrial neoplasia in tamoxifen-treated women with breast cancer: a transvaginal Doppler study". Ultrasound in Obstetric and Gynaecol., 1995, 6, 116.

[81] Alcazar J.L., Castillo G. et al.: "Endometrial blood flow mapping using trans vaginal power Doppler sonography in woman with postmenopausal bleeding and thickened endometrium". Ultrasound Obstet. Gynecol., 2003, 21, 583.

[82] Asher S.M., Johnson J.C., Zeman R.K., Patt R.H.: "Uterine changes in women receiving tamoxifen therapy: Prospective comparison of MRI and transvaginal sonography with pathologic correlation". Radiology, 1995, 197, 353.

[82] Goldstein S.R.: "Controversy about uterine effects and safety of SERMs: the saga continues". Menopause, 2002, 9, 381.

[83] Dallenbach-Hellweg G., Schmidt D. et al.: Arch. Gynecol. Obstet., 2000, 263, 170.

[84] Marttunen M.B., Cacciarote B. et al.: "Prospective study on gynaecological effects of two antiestrogens tamoxifen and toremifene in postmenopausal women". Brit. J. Cancer, 2001, 84, 897.

[85] Barakat R.R., Gilewski T. et al.: "The effect of adjuvant tamoxifen on the endometrium in women with breast cancer: A prospective study" Proc. Am. Soc. Clin. Oncol., 1999, 18, 358.

[86] Neven P., Vernaeve H.: Drug Safety, 2000, 22, 1.

[87] Guerrieri J.P.; Elkas J.C., Nash J.D.: "Evaluating the endometrium in women on tamoxifen: a pilot study to compare a'gold standard' with an 'old standard"'. Menopause, 1997, 4, 6.

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