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Geburtshilfe Frauenheilkd 2002; 62(11): 1053-1059
DOI: 10.1055/s-2002-35971
Übersicht

Georg Thieme Verlag Stuttgart · New York

Hormonersatztherapie bei Frauen nach Brustkrebserkrankung

Hormone Replacement Therapy in Breast Cancer SurvivorsC. Keck, C. Tempfer
  • Abteilung für Frauenheilkunde und Geburtshilfe, Universitätsklinikum Freiburg
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Publication History

Eingang Manuskript: 7. Februar 2002 Eingang revidiertes Manuskript: 7. Juni 2002

Akzeptiert: 20. August 2002

Publication Date:
05 December 2002 (online)

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Zusammenfassung

Etwa 70 % aller Frauen, die ein invasives Mammakarzinom in einem Frühstadium entwickeln und sich einer adäquaten Therapie unterziehen, werden diese Erkrankung überleben (10-JahresÜberlebensrate). Befragungen von Patientinnen mit Mammakarzinom zeigen, dass 8 % der Frauen nach Abschluss der Brustkrebstherapie eine Estrogenersatz- (ERT) oder eine Estrogen-Gestagenersatztherapie (HRT) eingenommen haben. Allerdings geben 44 % der Frauen an, sie würden gerne eine Hormonersatztherapie einnehmen. Die Ergebnisse der bisher vorliegenden klinischen Studien zeigen keinen negativen Einfluss einer ERT/HRT auf Rezidivrate und Gesamtüberleben bei Frauen nach Brustkrebs. Festzuhalten ist jedoch, dass zu dieser Fragestellung bisher keine prospektiv-randomisierte Studie vorliegt und die onkologische Sicherheit einer ERT/HRT nach Brustkrebs nicht belegt ist. Als Alternativen zu einer ERT/HRT kommen bei Brustkrebsüberlebenden mit klimakterischen Hormonmangelbeschwerden alternative Präparate wie Vitamin E, Clonidin, Megestrolazetat und Antidepressiva infrage. Diese Alternativen erreichen jedoch nicht die Wirksamkeit der HRT. Isoflavone und Traubensilberkerze (Cimicifuga racemosa) zeigten in prospektiv-randomisierten Studien an Brustkrebsüberlebenden keine stärkere Wirksamkeit als Plazebopräparate. Für Tibolon liegen keine Daten bei Brustkrebsüberlebenden vor.

Abstract

In patients with a diagnosis of early breast cancer, the 10-year survival rate can be expected to be 70 %. Approximately 8 % of patients with a history of breast cancer receive an oestrogen replacement therapy (ERT) or a combined replacement therapy (HRT). However, 44 % of the patients would like to take HRT. There is no convincing evidence for negative effects of ERT/HRT for patients with a history of breast cancer in terms of recurrence or survival rates. However, until today there are no prospective data available on long-term effects of ERT/HRT in breast cancer survivors. Thus, the oncological safety of this treatment is not proven and the risk/benefit ratio of HRT for breast cancer patients has not yet been clarified.

Besides ERT/HRT, placebo, vitamin E, clonidine, and megestrol acetate have been shown to significantly diminish vasomotor symptoms in postmenopausal breast cancer survivors, whereas isoflavones and black cohosh did not show a relief of symptoms in prospective randomised studies. There are no controlled data on the use of tibolone in breast cancer survivors.

Literatur

  • 1 Hayward J. The Guy's trial of treatments on “early” breast cancer.  World J Surgery. 1977;  1 314-316
    PubMedGoogle Scholar
  • 2 Brian D D, Melton L J, Goellner J R. Breast cancer incidence, prevalence, mortality, and survivorship in Rochester, Minnesota, 1935 - 1974.  Mayo Clin Proc. 1980;  55 355-359
    PubMedGoogle Scholar
  • 3 Lower E E, Blau R, Gazder P. et al . The risk of premature menopause induced by chemotherapy for early breast cancer.  J Womens Health Gend Based Med. 1999;  8 949-954
    PubMedGoogle Scholar
  • 4 Russo J, Tahin Q, Lareef M H, Hu Y F, Russo I CH. Neoplastic transformation of human breast epithelial cells by estrogens and chemical carcinogens.  Environ Mol Mutagen. 2002;  39 254-263
    CrossrefPubMedGoogle Scholar
  • 5 Russo J, Hu Y F, Tahin Q, Mihaila D, Slater C, Lareef M H, Russo I CH. .  APMIS. 2001;  109 39-52
    PubMed
  • 6 Yager J D, Liehr J G. Molecular mechnisms of estrogen carcinogenesis.  Annu Rev Pharmacol Toxicol. 1996;  36 203-232
    CrossrefPubMedGoogle Scholar
  • 7 Cavalieri E L, Stack D E, Devanesan P D, Todorovic R, Dwivedy I. Molecular origin of cancer-catechol estrogen-3, 4-quinones as endogenous tumor initiators.  Proc Natl Acad Sci USA. 1997;  94 10937-10942
    CrossrefPubMedGoogle Scholar
  • 8 Russo I H, Russo J. Role of hormones in mammary cancer initiation and progression.  J Mammary Gland Biol Neoplasia. 1998;  3 49-61
    CrossrefPubMedGoogle Scholar
  • 9 Noguchi M, Thomas M, Koyasaki N, Ohta N, Taniya T, Kitagawa H, Miyazaki I, Mizukami Y. .  Mol Cell Endocrinol. 1993;  92 69-76
    CrossrefPubMed
  • 10 Soto A M, Sonnenschein C. Mechanism of estrogen action on cellular proliferation: evidence for indirect and negative control on cloned breast tumor cells.  Biochem Biophys Res Commun. 1984;  122 1097-1103
    CrossrefPubMedGoogle Scholar
  • 11 Collaborative Group on hormonal factors in breast cancer . Breast cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiological studies of 52, 705 women with breast cancer and 108, 411 women without breast cancer.  Lancet. 1997;  350 1047-1059
    CrossrefPubMedGoogle Scholar
  • 12 Schairer C, Lubin J, Troisi R, Sturgeon S, Brinton L, Hoover R. Menopausal estrogen and estrogen-progestin replacement therapy and breast cancer risk.  JAMA. 2000;  283 485-491
    CrossrefPubMedGoogle Scholar
  • 13 Bush T L, Whiteman M, Flaws J A. Hormone replacement therapy and breast cancer: a qualitative review.  Obstet Gynecol. 2001;  98 498-508
    CrossrefPubMedGoogle Scholar
  • 14 Writing Group for The Women's Health Initiative Study Group . Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial.  JAMA. 2002;  288 321-333
    CrossrefPubMedGoogle Scholar
  • 15 Gapstur S M, Morrow M, Sellers T A. Hormone replacement therapy and risk of breast cancer with a favorable histology.  JAMA. 1999;  90 1371-1388
    PubMedGoogle Scholar
  • 16 Natrajan P K, Soumakis K, Gambrell R D. Estrogen replacement therapy in women with previous breast cancer.  Am J Obstet Gynecol. 1999;  181 288-295
    CrossrefPubMedGoogle Scholar
  • 17 Miki Y, Swenson J, Shattuck-Eidens D. et al . A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1.  Science. 1994;  66 71
    PubMedGoogle Scholar
  • 18 Wooster R, Bignell D, Lancester J. et al . Identification of the breast cancer susceptibility gene BRCA2.  Nature. 1996;  378 789-792
    PubMedGoogle Scholar
  • 19 Wu A H, Pike M C, Stram D O. Metaanalysis: diatary fat intake serum estrogen levels and risk of breast cancer.  J Natl Institute Health. 1999;  91 529-534
    PubMedGoogle Scholar
  • 20 Toniolo P G, Levitz M, Zeleniuch-Jacquotte A. et al . A prospective study of endogenous estrogens and breast cancer in postmenopausal women.  J Natl Cancer Inst. 1995;  87 190-197
    PubMedGoogle Scholar
  • 21 Cauley J A, Lucas F L, Kuller L H, Stone K, Browner W, Cummings S R. Elevated serum estradiol and testosterone concentrations are associated with a high risk for breast cancer.  Ann Intern Med. 1999;  130 270-277
    PubMedGoogle Scholar
  • 22 Vassilopoulou-Sellin R, Zolinski C. Estrogen replacement therapy in women with breast cancer: a survey of patient attitudes.  Am J Med Sci. 1992;  304 145-149
    PubMedGoogle Scholar
  • 23 Col N F, Hirota L K, Orr R K, Erban J K, Wang J B, Lau J. Hormone replacement therapy after breast cancer: a systematic review and quantitative assessment of risk.  J Clin Oncol. 2001;  19 2357-2363
    PubMedGoogle Scholar
  • 24 O'Meara E S, Rossing M A, Daling J R, Elmore J G, Barlow W E, Weiss N S. Hormone replacement therapy after a diagnosis of breast cancer in relation to recurrence and mortality.  J Nat Cancer Inst. 2001;  93 754-762
    CrossrefPubMedGoogle Scholar
  • 25 Braendle W, Schulz K D. Hormone und Mammakarzinom - Stellungnahme einer Konsensus-Konferenz. http://www.senologie.org/konsensu…hrt/hormone1997stellungnahme.htm. access date: 13 - 08 - 2002. 
    Google Scholar
  • 26 Powles T, Eeles R, Ashely 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
  • 27 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.  Lancet. 1998;  352 93-97
    PubMedGoogle Scholar
  • 28 Goldberg R M, Loprinzi C L, Fallon J R. Transdermal clonidine for ameliorating tamoxifen-induced hot flashes.  J Clin Oncol. 1994;  12 155-158
    PubMedGoogle Scholar
  • 29 Jacobson J S, Troxel A B, Evans J, Klaus L, Vahdat L, Kinne D, Lo K M, Moore A, Rosenman P J, Kaufman E L, Neugut A I, Grann V R. Randomized trial of black cohosh for the treatment of hot flashes among women with a history of breast cancer.  J Clin Oncol. 2001;  19 2739-2745
    PubMedGoogle Scholar
  • 30 Murphy P A, Song T, Buseman G. Isoflavones in retail and institutional soy foods.  J Agric Food Chem. 1999;  47 2697-2704
    CrossrefPubMedGoogle Scholar
  • 31 Markiewicz L, Garey J, Adlercreutz H, Gurpide E. In vitro bioassays of non-steroidal phytoestrogens.  J Steroid Biochem Mol Biol. 1993;  45 399-405
    CrossrefPubMedGoogle Scholar
  • 32 Makela S, Savolainen H, Aavik E, Myllarniemi M, Strauss L, Taskinen E, Gustafsson J A. Hayry P. Differentiation between vasculoprotective and uterotrophic effects of ligands with different binding affinities to estrogen receptors alpha and beta.  Proc Natl Acad Sci USA. 1999;  96 7077-7082
    CrossrefPubMedGoogle Scholar
  • 33 An J, Tzagarakis-Foster C, Scharschmidt T C, Lomri N, Leitman D C. Estrogen recepotor beta-selective transcriptional activity and recruitment of coregulators by phytoestrogens.  J Biol Chem. 2001;  276 17808-17814
    CrossrefPubMedGoogle Scholar
  • 34 Lu L W, Anderson K E, Grady J J, Kohen F, Nagamani M. Decreased ovarian hormones during a soya diet: implications for breast cancer prevention.  Cancer Res. 2000;  60 4112-4121
    PubMedGoogle Scholar
  • 35 Umland E M, Cauffield J S, Kirk J K, Thomason T E. Phytoestrogens as therapeutic alternatives to traditional hormone replacement in postmenopausal women.  Pharmacotherapy. 2000;  20 981-990
    CrossrefPubMedGoogle Scholar
  • 36 Brzezinski A. Menopause.  J N Am Menopausal Soc. 1997;  4 89-94
    PubMedGoogle Scholar
  • 37 Murkies A L. .  Maturitas. 1995;  21 189-195
    CrossrefPubMed
  • 38 Quella S K, Loprinzi C L, Barton D L. et al . Evaluation of soy phytoestrogens for the treatment of hot flashes in breast cancer survivors: a north central cancer treatment group trial.  JCO. 2000;  18(5) 1068-1074
    PubMedGoogle Scholar
  • 39 Barton D L, Loprinzi C L, Quella S K, Sloan J A, Veeder M H, Egner J R, Fidler P, Stella P J, Swan D K, Vaught N L, Novotny P. Prospective evaluation of vitamin E for hot flashes in breast cancer survivors.  J Clin Oncol. 1998;  16 495-500
    PubMedGoogle Scholar
  • 40 Goldberg R M, Loprinzi C L, O'Fallon J R, Veeder M H, Miser A W, Mailliard J A, Michalak J C, Dose A M, Rowland K M, Burnham N L. Transdermal clonidine for ameliorating tamoxifen-induced hot flashes.  J Clin Oncol. 1994;  12 155-158
    PubMedGoogle Scholar
  • 41 Pandya K J, Raubertas R F, Flynn P J, Hynes H E, Rosenbluth R J, Kirshner J J, Pierce H I, Dragalin V, Morrow G R. Oral clonidine in postmenopausal patients with breast cancer experiencing tamoxifen-induced hot flashes: a University of Rochester Cancer Center Community Clinical Oncology Program study.  Ann Intern Med. 2000;  132 788-793
    PubMedGoogle Scholar
  • 42 Charig C R, Rundle J S. Flushing: long-term side effect of orchiectomy in treatment of prostatic carcinoma.  Urology. 1989;  33 175-178
    CrossrefPubMedGoogle Scholar
  • 43 Erlik Y, Meldrum D R, Lagasse L D, Judd H L. Effect of megestrol acetate on flushing and bone metabolism in post-menopausal women.  Maturitas. 1981;  3 167-172
    PubMedGoogle Scholar
  • 44 Bullock J L, Massey F M, Gambrell R D. Use of medroxyprogesterone acetate to prevent menopausal symptoms.  Obstet Gynecol. 1975;  46 165-168
    PubMedGoogle Scholar
  • 45 Loprinzi C L, Michalak J C, Quella S K, O'Fallon J R, Hatfield A K, Nelimark R A, Dose A M, Fischer T, Johnson C, Klatt N E. et al . Megestrol acetate for the prevention of hot flashes.  N Engl J Med. 1994;  331 347-352
    CrossrefPubMedGoogle Scholar
  • 46 Quella S K, Loprinzi C L, Sloan J A, Vaught N L, DeKrey W L, Fischer T, Finck G, Pierson N, Pisansky T. Long term use of megestrol acetate by cancer survivors for the treatment of hot flashes.  Cancer. 1998;  82 1784-1788
    CrossrefPubMedGoogle Scholar
  • 47 Benghiat A, Cassidy S A, Davidson H E, Mancero F S, Pickard J G, Tyrrell C J. Megestrol acetate in the treatment of advanced post-menopausal breast cancer.  Eur J Surg Oncol. 1986;  12 43-45
    PubMedGoogle Scholar
  • 48 Wentz W B. Progestin therapy in lesions of the endometrium.  Semin Oncol. 1985;  12 (Suppl 1) 23-27
    PubMedGoogle Scholar
  • 49 Bonomi P, Pessis D, Bunting N. et al . Megestrol acetate used as primary hormonal therapy in stage D prostatic cancer.  Semin Oncol. 1985;  12 (Suppl 1) 36-39
    PubMedGoogle Scholar
  • 50 Jacobson J S, Troxel A B, Evans J, Klaus L, Vahdat L, Kinne D, Lo K M, Moore A, Rosenman P J, Kaufman E L, Neugut A I, Grann V R. Randomized trial of black cohosh for the treatment of hot flashes among women with a history of breast cancer.  J Clin Oncol. 2001;  19 2739-2745
    PubMedGoogle Scholar
  • 51 Loprinzi C L, Kugler J W, Sloan J A, Mailliard J A, LaVasseur B I, Barton D L, Novotny P J, Dakhil S R, Rodger K, Rummans T A, Christensen B J. Venlafaxine in management of hot flashes in survivors of breast cancer: a randomised controlled trial.  Lancet. 2000;  356 2059-2063
    CrossrefPubMedGoogle Scholar
  • 52 Ross L A, Alder E M. Tibolone and climacteric symptoms.  Maturitas. 1995;  21 127-136
    CrossrefPubMedGoogle Scholar
  • 53 Riggs B L. Tibolone as an alternative to estrogen for the prevention of postmenopausal osteoporosis in selected postmenopausal women.  J Clin Endocrinol Metab. 1996;  81 2417-2418
    CrossrefPubMedGoogle Scholar
  • 54 Chetrite G S, Pasqualini J R. The selective estrogen enzyme modulator (SEEM) in breast cancer.  J Steroid Biochem Mol Biol. 2001;  76 95-104
    CrossrefPubMedGoogle Scholar
  • 55 Chetrite G S, Kloosterboer H J, Philippe J C, Pasqualini J R. Effect of Org OD14 (LIVIAL) and its metabolites on human estrogen sulphotransferase activity in the hormone-dependent MCF-7 and T-47 D, and the hormone-independent MDA-MB-231, breast cancer cell lines.  Anticancer Res. 1999;  19 269-275
    PubMedGoogle Scholar
  • 56 Egarter C, Eppel W, Vogel S, Wolf G. A pilot study of hormone replacement therapy with tibolone in women with mastopathic breasts.  Maturitas. 2001;  40 165-171
    CrossrefPubMedGoogle Scholar

Leitender Oberarzt PD Dr. C. Keck

Universitäts-Frauenklinik

Hugstetter Straße 55

79106 Freiburg

Email: ckeck@frk.ukl.uni-freiburg.de

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