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
- 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
- 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
- 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
- 5
Russo J, Hu Y F, Tahin Q, Mihaila D, Slater C, Lareef M H, Russo I CH.
.
APMIS.
2001;
109
39-52
- 6
Yager J D, Liehr J G.
Molecular mechnisms of estrogen carcinogenesis.
Annu Rev Pharmacol Toxicol.
1996;
36
203-232
- 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
- 8
Russo I H, Russo J.
Role of hormones in mammary cancer initiation and progression.
J Mammary Gland Biol Neoplasia.
1998;
3
49-61
- 9
Noguchi M, Thomas M, Koyasaki N, Ohta N, Taniya T, Kitagawa H, Miyazaki I, Mizukami Y.
.
Mol Cell Endocrinol.
1993;
92
69-76
- 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
- 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
- 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
- 13
Bush T L, Whiteman M, Flaws J A.
Hormone replacement therapy and breast cancer: a qualitative review.
Obstet Gynecol.
2001;
98
498-508
- 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
- 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
- 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
- 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
- 18
Wooster R, Bignell D, Lancester J. et al .
Identification of the breast cancer susceptibility gene BRCA2.
Nature.
1996;
378
789-792
- 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
- 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
- 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
- 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
- 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
- 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
- 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.
- 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
- 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
- 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
- 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
- 30
Murphy P A, Song T, Buseman G.
Isoflavones in retail and institutional soy foods.
J Agric Food Chem.
1999;
47
2697-2704
- 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
- 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
- 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
- 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
- 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
- 36
Brzezinski A.
Menopause.
J N Am Menopausal Soc.
1997;
4
89-94
- 37
Murkies A L.
.
Maturitas.
1995;
21
189-195
- 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
- 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
- 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
- 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
- 42
Charig C R, Rundle J S.
Flushing: long-term side effect of orchiectomy in treatment of prostatic carcinoma.
Urology.
1989;
33
175-178
- 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
- 44
Bullock J L, Massey F M, Gambrell R D.
Use of medroxyprogesterone acetate to prevent menopausal symptoms.
Obstet Gynecol.
1975;
46
165-168
- 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
- 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
- 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
- 48
Wentz W B.
Progestin therapy in lesions of the endometrium.
Semin Oncol.
1985;
12 (Suppl 1)
23-27
- 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
- 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
- 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
- 52
Ross L A, Alder E M.
Tibolone and climacteric symptoms.
Maturitas.
1995;
21
127-136
- 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
- 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
- 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
- 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
Leitender Oberarzt PD Dr. C. Keck
Universitäts-Frauenklinik
Hugstetter Straße 55
79106 Freiburg
Email: ckeck@frk.ukl.uni-freiburg.de
