Zusammenfassung
Die aktuellen Therapieempfehlungen (8th International Conference on Primary Therapy of Early Breast Cancer, March 12-15,
2003 St. Gallen/Switzerland) bestätigen zum einen etablierte Therapien und lassen
gleichzeitig neue endokrine Therapien zu. So stellt der zeitlich begrenzte Hormonentzug
(2 Jahre Goserelin + 5 Jahre Tamoxifen) eine effektive Therapieoption bei prämenopausalen
Patientinnen mit einem hormonsensitiven Mammakarzinom dar und ist einer CMF-Chemotherapie
gleichwertig. Bei „sehr” jungen Frauen ist die adjuvante Chemotherapie allein nicht
ausreichend, sondern sollte durch eine endokrine Therapie ergänzt werden. Ein wesentlicher
Vorteil der endokrinen Therapie ist der nur zeitlich begrenzte Entzug endogener Hormone
und damit Schutz vor einer dauerhaften Ovarialinsuffizienz. In der Postmenopause wurde
Anastrozol (Arimidex™) als Alternative zu Tamoxifen für die adjuvante Behandlung postmenopausaler
Frauen mit hormonsensitivem, invasiven Mammakarzinom, die aufgrund eines erhöhten
Risikos für Thromboembolien oder wegen Veränderungen des Endometriums nicht mit Tamoxifen
behandelt werden können, zugelassen. Die endokrine Therapie sollte erst nach Abschluss
der Chemotherapie gegeben werden, da die simultane Gabe eine geringere Effektivität
zeigt. „Ältere” Patientinnen profitieren wahrscheinlich nicht von einer chemoendokrinen
gegenüber einer alleinigen endokrinen Therapie. Die vorläufigen Empfehlungen erlauben
eine recht große Therapiefreiheit.
Abstract
During the recently held 8th International Conference on Primary Therapy of Early Breast Cancer, (March 12-15,
2003 St. Gallen/Switzerland) established recommendations for adjuvant endocrine treatment
were confirmed, while new options were introduced. Ovarian ablation, limited for 2
years (e. g. Goserelin, combined with 5 years of Tamoxifen), was suggested as an effective
treatment option in premenopausal patients with a hormonsensitive breast cancer. The
efficacy of this endocrine regimen is equivalent to CMF-chemotherapy in these patients.
In “very” young patients with hormonsensitive tumors, chemotherapy alone is not sufficient.
These patients will particularly benefit from endocrine treatment. The reversibility
of endocrine treatment is its main advantage, avoiding long lasting symptoms of hormone
deficiency. In postmenopausal hormonsensitive patients the aromatase inhibitor Anastrozol
(Arimidex™) has been approved as an alternative for patients with contraindications
against Tamoxifen (e. g. increased risk of thromboembolism, varicosis, smokers, endometrium
changes). The initiation of endocrine should be postponed until the completion of
chemotherapy, because combined application reduces the efficacy of adjuvant treatment.
“Older” patients will get only limited advantage of chemoendocrine treatment compared
to endocrine treatment alone. Preliminary treatment recommendations comprise a wide
range of possible treatment options.
Schlüsselwörter
Mammakarzinom - Hormontherapie - Prämenopause - Postmenopause
Key words
Breast cancer - endocrine treatment - premenopause - postmenopause
Literatur
- 1
Aebi S, Gelber S, Castiglione-Gertsch M, Gelber R D, Collins J, Thurlimann B, Rudenstam C M,
Lindtner J, Crivellari D, Cortes-Funes H, Simoncini E, Werner I D, Coates A S, Goldhirsch A.
Is chemotherapy alone adequate for young women with oestrogen-receptor-positive breast
cancer?.
Lancet.
2000;
355
1869-1874
- 2
Albain K S. and for the intergroup study group .
Adjuvant chemohormonal therapy for primary primary breast cancer should be sequential
instead of concurrent: initial results from intergroup trial 0100 (SWOG-8813).
Proc Am Soc Clin Oncol.
2002;
21
144
- 3
Baum M.
Tamoxifen-the treatment of choice. Why look for alternatives?.
Br J Cancer.
1998;
78 (Suppl 4)
1-4
- 4
Baum M, Houghton J, Odling-Smee W, Rutqvist L E, Fornander T, Nordenskjold B, Nicolucci A,
Mark R J.
Adjuvant treatment of premenopausal breast cancer with zoladex and tamoxifen: Results
from randomized trials by the Cancer Research Campaign (CRC) Breast Cancer Trials
Group, The Stockholm Breast Cancer Study Group, The South East Sweden Breast Cancer
Group and Gruppo Interdisciplinare Valutazione Intervention Oncologica (GIVIO).
The Breast.
2001;
10 (Suppl 1)
64
- 5
Beatson G T.
On the treatment of inoperable cases of carcinoma of the mamma. Suggestions for a
new method of treatment with illustrative cases.
Lancet.
1896;
2
104-107
- 6
Ben Ayed F, Abaza S, Khalfallah S, Rais H, Mezline A, Riahi M, Ben Romdhane K.
Breast cancer in patients under 35 years of age.
Proc ASCO.
2002;
21
276
- 7
Bines J, Oleske D M, Cobleigh M A.
Ovarian function in premenopausal women treated with adjuvant chemotherapy for breast
cancer.
J Clin Oncol.
1996;
14
1718-1729
- 8
Blumenfeld Z.
Preservation of fertility and ovarian function and minimalization of chemotherapy
associated gonadotoxicity and premature ovarian failure: the role of inhibin-A and
-B as markers.
Mol Cell Endocrinol.
2002;
187
93-105
- 9
Boccardo F, Rubagotti A, Amoroso D, Mesiti M, Romeo D, Sismondi P, Giai M, Genta F,
Pacini P, Distante V, Bolognesi A, Aldrighetti D, Farris A.
Cyclophosphamide, methotrexate, and fluorouracil versus tamoxifen plus ovarian suppression
as adjuvant treatment of estrogen receptor-positive pre-/perimenopausal breast cancer
patients: results of the Italian Breast Cancer Adjuvant Study Group 02 randomized
trial. boccardo@ hp380.ist.unige.it.
J Clin Oncol.
2000;
18
2718-2727
- 10
Braverman A S, Sawhney H, Tendler A, Patel N, Rao C S.
Pre-menopausal serum estradiol levels may persist after chemotherapy-induced amenorrhea
in breast cancer.
Proc ASCO.
2002;
21
164
- 11
Burstein H J, Winer E P.
Primary care for survivors of breast cancer.
N Engl J Med.
2000;
343
1086-1094
- 12
Buzdar A. on behalf of the ATAC-trialists group .
The ATAC trial in postmenopausal women with early breast cancer - Updated efficacy
results based on a median follow-up of 47 months.
Breast Cancer Res Treat.
2002;
76 (Suppl 1)
32
- 13
Castiglione-Gertsch Mobo.
Is the addition of adjuvant chemotherapy always necessary in node negative pre/perimenopausal
breast cancer patientswho receive goserelin? First result of IBCSG trial VIII.
Proc ASCO.
2002;
21
149
- 14
Castiglione-Gertsch M M. on behalf of IBCSG co-workers .
Chemoendocrine therapy for node-negative breast cancer: IBCSG trial IX.
Breast Cancer Res Treat.
2002;
76 (Suppl 1)
31
- 15
Davidson N E, O'Neill A, Vukov A, Osborne C K, Martino S, White D, Abeloff M D.
Effect of chemohormonal therapy in premenopausal node positive, receptor positive
breast cancer: An Eastern Cooperative Oncology Group Phase III Intergroup trial (E5188,
Int-0101).
J Clin Oncol (Proceedings of ASCO).
1999;
18
67
- 16
Delmas P D, Balena R, Confravreux E, Hardouin C, Hardy P, Bremond A.
Bisphosphonate risedronate prevents bone loss in women with artificial menopause due
to chemotherapy of breast cancer: a double-blind, placebo-controlled study.
J Clin Oncol.
1997;
15
955-962
- 17
Di Leo A, Buyse M.
Equivalence between ovarian suppression and chemotherapy in the adjuvant treatment
of endocrine-responsive breast cancer.
J Clin Oncol.
2002;
20
1954-1955
- 18
EBCTCG .
Tamoxifen for early breast cancer: an overview of the randomised trials. Early Breast
Cancer Trialists' Collaborative Group.
Lancet.
1998;
351
1451-1467
- 19
Ejlertsen B, Dombernowsky P, Mouridsen H T, Kamby C, Kjaer M, Rose C, Knud A, Brit J M,
Olu B N, Bergh J.
Comparable effect of ovarian ablation and CMF chemotherapy on premenopausal hormone
receptor positive breast cancer patients.
Proc Am Soc Clin Oncol.
1999;
18
66
- 20
Fisher B, Jeong J-H, Bryant J, Mamounas E, Dignam J, Wolmark N.
Findings from two decades of NSABP clinical trials involving breast cancer patients
with negative axillary lymph nodes.
Breast Cancer Res Treat.
2002;
76 (Suppl 1)
32
- 21
Fox S B, Leek R D, Bliss J, Mansi J L, Gusterson B, Gatter K C, Harris A L.
Association of tumor angiogenesis with bone marrow micrometastases in breast cancer
patients.
J Natl Cancer Inst.
1997;
89
1044-1049
- 22
Goldhirsch A, Glick J H, Gelber R D, Coates A, Senn H J.
Meeting highlights: International consensus panel on the treatment of primary breast
cancer.
J Clin Oncol.
2001;
19
3817-3827
- 23
Hulley S, Furberg C, Barrett-Connor E, Cauley J, Grady D, Haskell W, Knopp R, Lowery M,
Satterfield S, Schrott H, Vittinghoff E, Hunninghake D.
Noncardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and
Estrogen/progestin Replacement Study follow-up (HERS II).
JAMA.
2002;
288
58-66
- 24
Jakesz R, Hausmaninger H, Kubista E, Gnant M, Menzel C, Bauernhofer T, Seifert M,
Haider K, Mlineritsch B, Steindorfer P, Kwasny W, Fridrik M, Steger G, Wette V, Samonigg H.
Randomized adjuvant trial of tamoxifen and goserelin versus cyclophosphamide, methotrexate,
and fluorouracil: evidence for the superiority of treatment with endocrine blockade
in premenopausal patients with hormone-responsive breast cancer - Austrian Breast
and Colorectal Cancer Study Group Trial 5.
J Clin Oncol.
2002;
20
4621-4627
- 25
Jonat W, Kaufmann M, Sauerbrei W, Blamey R, Cuzick J, Namer M, Fogelman I, de Haes J C,
de Matteis A, Stewart A, Eiermann W, Szakolczai I, Palmer M, Schumacher M, Geberth M,
Lisboa B.
Goserelin versus cyclophosphamide, methotrexate, and fluorouracil as adjuvant therapy
in premenopausal patients with node-positive breast cancer: The Zoladex Early Breast
Cancer Research Association Study.
J Clin Oncol.
2002;
20
4628-4635
- 26
Kauff N D, Satagopan J M, Robson M E, Scheuer L, Hensley M, Hudis C A, Ellis N A,
Boyd J, Borgen P I, Barakat R R, Norton L, Castiel M, Nafa K, Offit K.
Risk-reducing salpingo-oophorectomy in women with a BRCA1 or BRCA2 mutation.
N Engl J Med.
2002;
346
1609-1615
- 27
Klijn J G, Blamey R W, Boccardo F, Tominaga T, Duchâteau L, Sylvester R.
Combined tamoxifen and luteinizing hormone-releasing hormone (LHRH) agonist versus
LHRH agonist alone in premenopausal advanced breast cancer: a meta-analysis of four
randomized trials.
J Clin Oncol.
2001;
19
343-353
- 28
Kroman N, Jensen M B, Wohlfahrt J, Mouridsen H T, Andersen P K, Melbye M.
Factors influencing the effect of age on prognosis in breast cancer: population based
study.
BMJ.
2000;
320
474-478
- 29
Love R R, Duc N B, Allred D C, Binh N C, Dinh N V, Kha N N, Thuan T V, Mohsin S K,
Roanh l D, Khang H X, Tran T L, Quy T T, Thuy N V, The P N, Cau T T, Tung N D, Huong D T,
Quang L M, Hien N N, Thuong L, Shen T Z, Xin Y, Zhang Q, Havighurst T C, Yang Y F,
Hillner B E, DeMets D L.
Oophorectomy and tamoxifen adjuvant therapy in premenopausal Vietnamese and Chinese
women with operable breast cancer.
J Clin Oncol.
2002;
20
2559-2566
- 30
Love R R, Duc N B, Dinh N V, Quy T T, Xin Y, Havighurst T C.
Young age as an adverse prognostic factor in premenopausal women with operable breast
cancer.
Clin Breast Cancer.
2002;
2
294-298
- 31
Minton S E, Munster P N.
Chemotherapy-induced amenorrhea and fertility in women undergoing adjuvant treatment
for breast cancer.
Cancer Control.
2002;
9
466-472
- 32
Nabholtz J, Pienkowski T, Mackey J, Pawlicki M, Guastalla J P, Vogel C, Weaver C,
Walley M.
Phase III trial comparing TAC (docetaxel, doxorubicin, cyclophosphamide) with FAC
(5- fluorouracil, doxorubicin, cyclophosphamide) in the adjuvant treatment of node
poitive breast cancer patients: interim analysis of the BCIRG 001 study.
Proc ASCO.
2002;
21
141
- 33
NIH .
National Institutes of Health Consensus Development Conference statement: adjuvant
therapy for breast cancer, November 1-3, 2000.
J Natl Cancer Inst Monogr.
2001;
1
5-15
- 34
Peto R, Boreham J, Clarke M, Davies C, Beral V.
UK and USA breast cancer deaths down 25 % in year 2000 at ages 20-69 years.
Lancet.
2000;
355
1822
- 35
Poikonen P, Saarto T, Elomaa I, Joensuu H, Blomqvist C.
Prognostic effect of amenorrhoea and elevated serum gonadotropin levels induced by
adjuvant chemotherapy in premenopausal node-positive breast cancer patients.
Eur J Cancer.
2000;
36
43-48
- 36
Powles T J, McCloskey E, Paterson A H, Ashley S, Tidy V A, Nevantaus A, Rosenqvist K,
Kanis J.
Oral clodronate and reduction in loss of bone mineral density in women with operable
primary breast cancer.
J Natl Cancer Inst.
1998;
90
704-708
- 37
Pritchard K I.
Adjuvant therapy for premenopausal women with breast cancer: is it time for another
paradigm shift?.
J Clin Oncol.
2002;
20
4611-4614
- 38
Rebbeck T R, Lynch H T, Neuhausen S L, Narod S A, Van 't Veer L, Garber J E, Evans G,
Isaacs C, Daly M B, Matloff E, Olopade O I, Weber B L.
Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations.
N Engl J Med.
2002;
346
1616-1622
- 39
Recchia F, Sica G, De Filippis S, Saggio G, Rosselli M, Rea S.
Goserelin as ovarian protection in the adjuvant treatment of premenopausal breast
cancer: a phase II pilot study.
Anticancer Drugs.
2002;
13
417-424
- 40
Reid I R, Brown J P, Burckhardt P, Horowitz Z, Richardson P, Trechsel U, Widmer A,
Devogelaer J P, Kaufman J M, Jaeger P, Body J J, Brandi M L, Broell J, Di Micco R,
Genazzani A R, Felsenberg D, Happ J, Hooper M J, Ittner J, Leb G, Mallmin H, Murray T,
Ortolani S, Rubinacci A, Saaf M, Samsioe G, Verbruggen L, Meunier P J.
Intravenous zoledronic acid in postmenopausal women with low bone mineral density.
N Engl J Med.
2002;
346
653-661
- 41
Roche H, Kerbrat P, Bonneterre J, Fargeot P, Fumoleau P, Monnier A, Chappele-Marcillac I,
Bardonnet M.
Complete hormonal blockadeversus chemotherapy in premenopausal early stage breast
cancer patients with positive hormone receptor and 1-3 node-positive tumor, result
of the FASG 06 trial.
Proc Am Soc Clin Oncol.
2000;
19
72
- 42
Saarto T, Blomqvist C, Valimaki M, Makela P, Sarna S, Elomaa I.
Chemical castration induced by adjuvant cyclophosphamide, methotrexate, and fluorouracil
chemotherapy causes rapid bone loss that is reduced by clodronate: a randomized study
in premenopausal breast cancer patients.
J Clin Oncol.
1997;
15
1341-1347
- 43
Schimmer A D, Quatermain M, Imrie K, Ali V, McCrae J, Stewart A K, Crump M, Derzko C,
Keating A.
Ovarian function after autologous bone marrow transplantation.
J Clin Oncol.
1998;
16
2359-2363
- 44
Schinzinger K.
Über Carcinoma mammae.
Zbl Chirurgie.
1889;
16
55
- 45
Aaaa A.
Scottish Cancer Trials Breast Group and ICRF Breast Unit GH: Adjuvant ovarian ablation
versus CMF chemotherapy in premenopausal women with pathological stage II breast carcinoma:
the Scottish trial. Scottish Cancer Trials Breast Group and ICRF Breast Unit, Guy
's Hospital, London.
Lancet.
1993;
341
1293-1298
- 46
Shapiro C L, Manola J, Leboff M.
Ovarian failure after adjuvant chemotherapy is associated with rapid bone loss in
women with early-stage breast cancer.
J Clin Oncol.
2001;
19
3306-3311
- 47
Vehmanen L, Saarto T, Elomaa I, Makela P, Valimaki M, Blomqvist C.
Long-term impact of chemotherapy-induced ovarian failure on bone mineral density (BMD)
in premenopausal breast cancer patients. The effect of adjuvant clodronate treatment.
Eur J Cancer.
2001;
37
2373-2378
Prof. Dr. med. B. Gerber
I. Frauenklinik der LMU München
Maistraße 11
80337 München
eMail: bernd.gerber@fk-i.med.uni-muenchen.de
