Download PDF
Geburtshilfe Frauenheilkd 2002; 62(8): 743-749
DOI: 10.1055/s-2002-33718
Übersicht

Georg Thieme Verlag Stuttgart · New York

Wirkungen von Tamoxifen auf das Endometrium

Effects of Tamoxifen on the EndometriumA. Schultze-Mosgau, K. Diedrich, O. Ortmann
  • Klinik für Frauenheilkunde und Geburtshilfe, Medizinische Universität Lübeck, Lübeck
Further Information

Publication History

Eingang Manuskript: 5. Juli 2002 Eingang revidiertes Manuskript: 12. Juli 2002

Akzeptiert: 13. Juli 2002

Publication Date:
29 August 2002 (online)

Also available at
    Permissions and Reprints

Zusammenfassung

Das Antiöstrogen Tamoxifen wird seit etwa 20 Jahren erfolgreich in der adjuvanten und palliativen Therapie des hormonrezeptorpositiven Mammakarzinoms eingesetzt.

Im Rahmen von randomisierten Studien wurde ein gehäuftes Auftreten von Endometriumkarzinomen unter der Tamoxifenbehandlung beobachtet, wobei das relative Risiko als zwischen 2 und 8fach erhöht beschrieben wurde. Die östrogene Aktivität am Endometrium kann zu pathologischen Veränderungen, wie z. B. Hyperplasien oder Karzinomen, führen. Der Nutzen einer adjuvanten Therapie mit Tamoxifen überwiegt jedoch gegenüber dem Risiko. Trotzdem verursacht die endometriale Wirkung der Substanz teilweise erhebliche Verunsicherung. In der folgenden Übersicht wird die Wirkungsweise von Tamoxifen auf das Endometrium erläutert. Eine Literaturübersicht stellt den derzeitigen Kenntnisstand zu den klinisch relevanten endometrialen Veränderungen und den praktischen Umgang mit Tamoxifenanwenderinnen dar.

Abstract

For about 20 years the antiestrogen tamoxifen is successfully used in the adjuvant and palliative treatment of estrogen receptor-positive breast cancer. Randomised trials showed an increased risk for the development of endometrial cancer related to tamoxifen. There is an 2 - 8fold increased relative risk. The estrogen-activity results in endometrial changes, like hyperplasia or carcinoma. On the contrary the benefit of tamoxifen in the adjuvant treatment overweighs its risks. Nevertheless the effects of the substance on the endometrium make patients feel uncomfortable. In this review we explain mechanisms of tamoxifens action on the endometrium. A review of literature shows the latest skills of clinical relevant endometrial changes and gives practical advice for the approach to patients using tamoxifen.

Literatur

  • 1 Anderson L F. Cancer act anniversary encourages reflection, new visions [news].  J Natl Cancer Inst. 1991;  83 1795-1796
    PubMedGoogle Scholar
  • 2 Andersson M, Storm H H, Mouridsen H T. Incidence of new primary cancers after adjuvant tamoxifen therapy and radiotherapy for early breast cancer.  J Natl Cancer Inst. 1991;  83 1013-1017
    PubMedGoogle Scholar
  • 3 Andersson M, Storm H H, Mouridsen H T. Carcinogenic effects of adjuvant tamoxifen treatment and radiotherapy for early breast cancer.  Acta Oncol. 1992;  31 271-274
    PubMedGoogle Scholar
  • 4 Bergman U, Beelen M, Gallee M. Risk and prognosis of endometrial cancer after tamoxifen for breast cancer.  Lancet. 2000;  356 881-887
    CrossrefPubMedGoogle Scholar
  • 5 Bernstein L, Deapen D, Cerhan J R, Schwartz S M, Liff J, McGann-Maloney E, Perlman J A, Ford L. Tamoxifen therapy for breast cancer and endometrial cancer risk.  J Natl Cancer Inst. 1999;  91 1654-1662
    CrossrefPubMedGoogle Scholar
  • 6 Boccardo F, Rubagotti A, Bruzzi P. et al . Chemotherapy versus tamoxifen versus chemotherapy plus tamoxifen in node-positive, estrogen receptor-positive breast cancer patients: results of a multicentric Italian study. Breast Cancer Adjuvant Chemo-Hormone Therapy Cooperative Group.  J Clin Oncol. 1990;  8 1310-1320
    PubMedGoogle Scholar
  • 7 Carmichael P L, Ugwumadu A HN, Neven P, Hewer A J, Poon G K, Phillips D H. Lack of genotoxicity of tamoxifen in human endometrium.  Cancer Res. 1996;  56 1475-1479
    PubMedGoogle Scholar
  • 8 Castiglione M, Gelber R D, Goldhirsch A. Adjuvant systemic therapy for breast cancer in the elderly: competing causes of mortality. International Breast Cancer Study Group.  J Clin Oncol. 1990;  8 519-526
    PubMedGoogle Scholar
  • 9 Cecchini S, Ciatto S, Bonardi R, Mazzotta A, Grazzini G, Pacini P, Muraca M G. Screening by ultrasonography for endometrial carcinoma in postmenopausal breast cancer patients under adjuvant tamoxifen.  Gynecol Oncol. 1996;  60 409-411
    CrossrefPubMedGoogle Scholar
  • 10 Cook L S, Weiss N S, Schwartz S M. et al . Population-based study of tamoxifen therapy and subsequent ovarian, endometrial and breast cancers.  J Natl Cancer Inst. 1995;  87 1359-1364
    PubMedGoogle Scholar
  • 11 Cuenca R E, Giachino J, Arredondo M A. et al . Endometrial carcinoma associated with breast carcinoma: Low incidence with tamoxifen use.  Cancer. 1996;  77 2058-2063
    CrossrefPubMedGoogle Scholar
  • 12 Cummings F J, Gray R, Torney D C. et al . Adjuvant tamoxifen versus placebo in elderly women with node-positive breast cancer: long-term follow-up and causes of death.  J Clin Oncol. 1993;  11 29-35
    PubMedGoogle Scholar
  • 13 Curtis R E, Boice J D, Shriner D A. et al . Second cancers after adjuvant tamoxifen therapy for breast cancer.  J Natl Cancer Inst. 1996;  88 832-834
    PubMedGoogle Scholar
  • 14 Early Breast Cancer Trialists Collaborative Group . Tamoxifen for early breast cancer: an overview of the randomised trials.  Lancet. 1998;  351 1451-1467
    CrossrefPubMedGoogle Scholar
  • 15 Fisher B, Costantino 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;  86 527-537
    PubMedGoogle Scholar
  • 16 Fisher B. Commentary on endometrial cancer deaths in tamoxifen-treated breast cancer patients.  J Clin Oncol. 1996;  14 1027-1039
    PubMedGoogle Scholar
  • 17 Fisher B, Dignam J, Bryant J, DeCillis A, Wickerham D L, Wolmark N, Costantino J, Redmond C, Fisher E R, Bowman D M, Deschenes L, Dimitrov N V, Margolese R G, Robidoux A, Shibata H, Terz J, Paterson A H, Feldman M I, Farrar W, Evans J, Lickley H L. Five versus more than five years of tamoxifen therapy for breast cancer patients with negative lymph nodes and estrogen receptor-positive tumors.  J Natl Cancer Inst. 1996;  88 1529-1542
    CrossrefPubMedGoogle Scholar
  • 18 Fisher B, Costantino J P, Wickerham D L, Redmond C K, Kavanah M, Cronin W M, Vogel V, Robidoux A, Dimitrov N, Atkins J, Daly M, Wieand S, Tan-Chiu E, Ford L, Wolmark N. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study.  J Natl Cancer Inst. 1998;  90 1371-1388
    CrossrefPubMedGoogle Scholar
  • 19 Fornander T, Rutqvist L E, Cedermark B, Glas U, Mattsson A, Silfversward C, Skoog L, Somell A, Theve T, Wilking N. et al . Adjuvant tamoxifen in early breast cancer: occurrence of new primary cancers.  Lancet. 1989;  1 117-120
    PubMedGoogle Scholar
  • 20 Fornander T, Hellstrom A C, Moberger B. Descriptive clinicopathologic study of 17 patients with endometrial cancer during or after adjuvant tamoxifen in early breast cancer.  J Natl Cancer Inst. 1993;  85 1850-1855
    PubMedGoogle Scholar
  • 21 Franchi M, Ghezzi F, Donadello N, Zanaboni F, Beretta P, Bolis P. Endometrial thickness in tamoxifen-treated patients: an independent predictor of endometrial disease.  Obstet Gynecol. 1999;  93 1004-1008
    CrossrefPubMedGoogle Scholar
  • 22 Gallo M A, Kaufman D. Antagonistic and agonistic effects of tamoxifen: significance in human cancer.  Semin Oncol. 1997;  24 (Suppl 1) S1-71-S1-80
    PubMedGoogle Scholar
  • 23 Gelmon K. One step forward or one step back with tamoxifen?.  Lancet. 2000;  356 868-869
    CrossrefPubMedGoogle Scholar
  • 24 Hardell L. Pelvic irradiation and tamoxifen as risk factors for carcinoma of corpus uteri.  Lancet. 1988;  2 1432
    PubMedGoogle Scholar
  • 25 Hardell L. Tamoxifen as risk factor for carcinoma of corpus uteri.  Lancet. 1988;  2 563
    PubMedGoogle Scholar
  • 26 Hardell L. Tamoxifen as risk factor for endometrial cancer.  Cancer. 1990;  66 1661
    PubMedGoogle Scholar
  • 27 Hoover R, Fraumeni J F, Everson R, Myers M H. Cancer of the uterine corpus after hormonal treatment for breast cancer.  Lancet. 1976;  1 885-887
    PubMedGoogle Scholar
  • 28 Horn L C, Lax S F, Höckel M, Fischer U, Schmidt D. Präkanzeröse Läsionen des Endometriums: Aspekte der molekularen Pathogenese und Probleme der Nomenklatur.  Geburtsh Frauenheilk. 2001;  61 8-14
    Article in Thieme ConnectPubMedGoogle Scholar
  • 29 Hubay C A, Gordon N H, Pearson O H. et al . Eight-year follow-up of adjuvant therapy for stage II breast cancer.  World J Surg. 1985;  9 738-749
    CrossrefPubMedGoogle Scholar
  • 30 Killackey M A, Hakes T B, Pierce V K. Endometrial adenocarcinoma in breast cancer patients receiving antiestrogens.  Cancer Treat Rep. 1985;  69 237-238
    PubMedGoogle Scholar
  • 31 Van Leeuwen F E, Benraadt J, Coebergh J W. et al . Risk of endometrial cancer after tamoxifen treatment of breast cancer.  Lancet. 1994;  343 448-452
    CrossrefPubMedGoogle Scholar
  • 32 Love R, Muir B B, Scrimgeour J B, Leonard R CF, 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 2050-2054
    PubMedGoogle Scholar
  • 33 Mader U. Tamoxifen beim Mammakarzinom: Risiko eines Endometrium-Karzinoms.  Geburtsh Frauenheilk. 2001;  61 A35-A36
    Article in Thieme ConnectPubMedGoogle Scholar
  • 34 Powles T J, Jones A L, Ashley S E. et al . The Royal Marsden Hospital pilot tamoxifen chemoprevention trial.  Breast Cancer Res Treat. 1994;  31 73-82
    CrossrefPubMedGoogle Scholar
  • 35 Petru E, Kurschel S, Walsberger K. Screening asymptomatischer Frauen auf Endometriumkarzinom mit besonderer Berücksichtigung des Screenings unter Tamoxifen-Behandlung.  Geburtsh Frauenheilk. 2000;  60 297-301
    Article in Thieme ConnectPubMedGoogle Scholar
  • 36 Powles T, Eeles R, Ashley S, Easton D, Chang J, Dowsett M, Tidy A, Viggers J, Davey J. Interim analysis of the incidence of breast cancer in the Royal Marsden Hospital tamoxifen randomised chemoprevention trial.  Lancet. 1998;  352 98-101
    PubMedGoogle Scholar
  • 37 Powles T J, Bourne T, Athanasiou S, Chang J, Grubock K, Ashley S, Oakes L, Tidy A, Davey J, Viggers J, Humphries S, Collins W. The effects of norethisterone on endometrial abnormalities identified by transvaginal ultrasound screening of healthy post-menopausal women on tamoxifen or placebo.  Br J Cancer. 1998;  78 272-275
    PubMedGoogle Scholar
  • 38 Ribeiro G, Swindell R. The Christie Hospital adjuvant tamoxifen trial. Status at 10 years.  Br J Cancer. 1988;  57 601-603
    PubMedGoogle Scholar
  • 39 Ribeiro G, Swindell R. The Christie Hospital adjuvant tamoxifen trial.  Monogr Natl Cancer Inst. 1992;  11 121-125
    PubMedGoogle Scholar
  • 40 Robinson D C, Bloss J D, Schiano M A. A retrospective study of tamoxifen and endometrial cancer in breast cancer patients.  Gynecol Oncol. 1995;  59 186-190
    CrossrefPubMedGoogle Scholar
  • 41 Rutqvist L E, Johansson H, Signomklao T, Johansson U, Fornander T, Wilking N. Adjuvant tamoxifen therapy for early stage breast cancer and second primary malignancies. Stockholm Breast Cancer Study Group.  J Natl Cancer Inst. 1995;  87 645-651
    PubMedGoogle Scholar
  • 42 Ryden S, Ferno M, Moller T, Aspegren K, Bergljung L, Killander D, Landberg T. Long-term effects of adjuvant tamoxifen and/or radiotherapy. The South Sweden Breast Cancer Trial.  Acta Oncol. 1992;  31 271-274
    PubMedGoogle Scholar
  • 43 Sasco A J, Chaplain G, Amoros E. et al . Endometrial cancer following breast cancer: Effect of tamoxifen and castration by radiotherapy.  Epidemiology. 1996;  7 9-13
    PubMedGoogle Scholar
  • 44 Schultze-Mosgau A, Montzka P, Krüger S, Bauer O, Ortmann O, Diedrich K. Zur Prävalenz von hyperplastischen und neoplastischen Veränderungen des Endometriums bei postmenopausalen Patientinnen mit Mammakarzinom vor Tamoxifentherapie.  Geburtsh Frauenheilk. 1999;  59 606-610
    Article in Thieme ConnectPubMedGoogle Scholar
  • 45 Stearns V, Gelmann E P. Does tamoxifen cause cancer in humans?.  J Clin Oncol. 1998;  16 779-792
    PubMedGoogle Scholar
  • 46 Stewart H J. The Sottish trial of adjuvant tamoxifen in node-negative breast cancer. Scottish cancer trials Breast Group.  Monogr Natl Cancer Inst. 1992;  11 117-120
    PubMedGoogle Scholar
  • 47 Touraine P, Driguez P, Castier I. et al . Lack of induction of endometrial hyperplasia with tamoxifen.  Lancet. 1995;  345 254-255
    CrossrefPubMedGoogle Scholar
  • 48 Veronesi U, Maisonneuve P, Costa A, Sacchini V, Maltoni C, Robertson C, Rotmensz N, Boyle P. Prevention of breast cancer with tamoxifen: preliminary findings from the Italian randomised trial among hysterectomised women. Italian Tamoxifen Prevention Study.  Lancet. 1998;  352 93-97
    PubMedGoogle Scholar

Prof. Dr. med. Olaf Ortmann

Klinik für Frauenheilkunde und Geburtshilfe, Medizinische Universität Lübeck

Ratzeburger Allee 160

23538 Lübeck

Email: ortmann@medinf.mu-luebeck.de