RSS-Feed abonnieren
DOI: 10.1055/s-2002-25170
Systemtherapie beim Mammakarzinom -
Adjuvante und neoadjuvante Therapie:
Aktueller Stand, aktuelle Studien
Systemic therapy in breast cancer - adjuvant and neo-adjuvant treatment: Update situation and update studies
Publikationsverlauf
Publikationsdatum:
18. April 2002 (online)
Zusammenfassung
Der Einsatz adjuvanter systemischer Therapien geht beim Mammakarzinom mit einer klaren Senkung der Rezidivwahrscheinlichkeit und einer Verlängerung des Gesamtüberlebens einher. Die adjuvante Behandlung sollte sich an den Konsensusempfehlungen von St. Gallen 2001 orientieren. Entscheidende prognostische und prädiktive Parameter für die Therapiewahl sind die Tumorgröße, das Ausmaß des axillären Lymphknotenbefalls, der Menopausenstatus, der Hormonrezeptorstatus und das Grading. Bei der Mehrzahl der Patientinnen, insbesondere bei Frauen mit hormonunempfindlichen Tumoren, ist eine adjuvante Chemotherapie indiziert. Anthrazyklinhaltige Therapien weisen einen kleinen, aber statistisch signifikanten Überlebensvorteil gegenüber nicht-anthrazyklinhaltigen Therapieprotokollen auf. Neuere Daten weisen der adjuvanten Hormontherapie einen hohen Stellenwert zu. Mit Ausnahme einer kleinen Gruppe von Patientinnen mit minimaler Rückfallwahrscheinlichkeit sollten alle Frauen mit hormonempfindlichen Tumoren eine antihormonelle Therapie erhalten. Grundlage ist eine Tamoxifen-Behandlung über 5 Jahre. Für prämenopausale Frauen stellt die Ausschaltung der Ovarialfunktion eine zusätzliche Option dar. Nicht abschließend geklärt ist derzeit die Frage der kombinierten Hormontherapie bzw. chemoendokriner Therapien bei Patientinnen mit hormonempfindlichen Tumoren. Der Stellenwert von Trastuzumab bzw. der Aromatasehemmer und der Bisphosphonate ist derzeit unklar. Präoperative medikamentöse Therapien sind beim inflammatorischen Mammakarzinom die Behandlungsform der Wahl. Multimodale Therapiekonzepte ermöglichen dabei eine Verlängerung der Überlebenszeit. Bei nicht-inflammatorischen Mammakarzinomen sind durch den Einsatz primärer systemischer Therapien organerhaltende Operationen häufiger möglich. Zudem ermöglichen sie eine Verbesserung prognostischer Aussagen und eine rasche Evaluierung neuer Therapieverfahren. Ein Überlebensvorteil ließ sich bei nicht-inflammatorischen Tumoren nicht nachweisen. Patientinnen mit einer pathologisch kompletten Remission nach der präoperativen Behandlung scheinen jedoch eine bessere Prognose aufzuweisen. Ausgenommen lokal fortgeschrittene Tumore, sollten präoperative medikamentöse Therapien klinischen Studien vorbehalten sein.
Abstract
Adjuvant systemic treatment has made a major impact on relapse-free and overall survival of patients with early-stage breast cancer. Recommendations for adjuvant treatment have been proposed by an international consensus panel in St. Gallen 2001. Treatment strategies are based on prognostic and predictive factors including tumour size, nodal status, menopausal status, hormone receptor status and grading. Adjuvant polychemotherapy is indicated in the majority of patients, especially in women with hormone-insensitive disease. Anthracycline-based regimens have been associated with a small but statistically significant advantage in overall survival compared to CMF-based regimens. Recent developments enhance the role of endocrine treatments. With the exception of patients with minimal-risk disease, all women with hormone-sensitive disease should be considered for hormonal therapy. Tamoxifen for 5 years is the most established adjuvant hormonal treatment. Ovarian ablation or suppression of the ovarian function are further promising options for premenopausal women. The role of combined hormonal or chemoendocrine treatment is currently unclear. The role of adjuvant treatment with trastuzumab, aromatase inhibitors or bisphosphonates has yet to be defined. Primary systemic therapy has become the treatment of choice for inflammatory breast cancer since combined modality approaches resulted in an improved survival. In non-inflammatory breast cancer, primary systemic treatment has generally failed to show an impact on survival. Only pathological complete response to primary treatment seems to be associated with a better prognosis. The use of primary systemic therapy can result in more frequent usage of breast conserving modalities. However, outside clinical trials, the use of preoperative systemic therapy should be restricted to locally-advanced disease.
Schlüsselwörter
Mammakarzinom - Adjuvante Therapie - Neoadjuvante Therapie - Tamoxifen - GURH-Analoga
Key words
Primary breast cancer - adjuvant treatment - primary systemic therapy - tamoxifen - ovarian ablation
Literatur
- 1 Hutchins L, Green S, Ravdin P. et al . CMF Versus CAF With And Without Tamoxifen In High-Risk Node-Negative Breast Cancer Patients And A Natural History Follow-Up Study In Low-Risk Node-Negative Patients: First Results Of Intergroup Trial Int 0102. Proc Am Soc Clin Oncol. 1998; 17 1
- 2 Early Breast Cancer Trialists' Collaborative Group . Effects of adjuvant tamoxifen and of cytotoxic therapy on mortality in early breast cancer: An overview of 61 randomized trials among 28,896 women. N Engl J Med. 1998; 319 1681-1692
- 3 Early Breast Cancer Trialists' Collaborative Group . Polychemotherapy for early breast cancer: an overview of the randomised trials. Lancet. 1998; 352 930-942
- 4 Bonadonna G, Valagussa P. Dose-response effect of adjuvant chemotherapy in breast cancer. N Engl K Med. 1981; 304 (1) 10-15
- 5 Budman D R, Berry D A, Cirrincione C T. et al . Dose and dose intensity as determinants of outcome in the adjuvant treatment of breast cancer. The Cancer and Leukemia Group B. J Natl Cancer Inst.. 1998; 90 (16) 1205-1211
- 6 Fisher B, Anderson S, Wickerham D L. et al . Increased intensification and total dose of cyclophosphamide in a doxorubicin-cyclophosphamide regimen for the treatment of primary breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-22. J Clin Oncol.. 1997; 15 (5) 1858-1869
- 7 French Epirubicin Study Group . A prospective randomized trial comparing epirubicin monochemotherapy to two fluorouracil, cyclophosphamide, and epirubicin regimens differing in epirubicin dose in advanced breast cancer patients. J Clin Oncol. 1991; 9 305-312
- 8 Bonneterre J, Roche H, Bremond A. A randomized trial of adjuvant chemotherapy with FEC 50 vs. FEC 100 for node-positive operable breast cancer early report. Proc Am Soc Clin Oncol. 1996; 15 104
- 9 Bastholt L, Dalmark M, Gjedde S. et al . Dose-response relationship of epirubicin in the treatment of postmenopausal patients with metastatic breast cancer: A randomized study of epirubicin at four different dose levels performed by the Danish Breast Cancer Cooperative Group. J Clin Oncol. 1996; 14 1146-1155
- 10 Marschner N, Kreienberg R, Souchon R. et al . Evaluation of the importance and relevance of dose intensity using epirubicin and cyclophosphamide in metastatic breast cancer: Interim analysis of a prospective randomized trial. Semin Oncol. 1994; 21 10-16
- 11 Focan C, Andrien J M, Closon M T. et al . Dose-response relationship of epirubicin-based first-line chemotherapy for advanced breast cancer: A prospective randomized trial. J Clin Oncol. 1993; 11 1253-1263
- 12 Brufman G, Colajori E, Ghilezan N. et al . Doubling epirubicin dose intensity (100 mg/m2 versus 50 mg/m2) in the FEC regimen significantly increases response rates: An international randomized phase III study in metastatic breast cancer. Ann Oncol. 1997; 8 155-162
- 13 French Epirubicin Study Group . Epirubicin-based chemotherapy in metastatic breast cancer patients: role of dose-intensity and duration of treatment. J Clin Oncol. 2000; 18 3115-3124
- 14 Hortobagyi G N, Buzdar A U, Theriault R L. et al . Randomized trial of high-dose chemotherapy and blood cell autografts for high-risk primary breast carcinoma. J Natl Cancer Inst. 2000; 92 225-233
- 15 Bergh J, Wiklund T, Erikstein B. et al . Tailored fluorouracil, epirubicin, and cyclophosphamide compared with marrow-supported high-dose chemotherapy as adjuvant treatment for high-risk breast cancer: a randomised trial. Lancet. 2000; 356 1384-1391
- 16 Rodenhuis S, Richel D, van der Wall E. et al . Randomised trial of high-dose chemotherapy and haemopoietic progenitor-cell support in operable breast cancer with extensive axillary lymph-node involvement. Lancet. 1998; 352 515-521
- 17 Tokuda Y, Tajima T, Narabayashi M. et al . Randomized phase III study of high-dose chemotherapy (hdc) with autologous stem cell support as consolidation in high-risk postoperative breast cancer: japan clinical oncology group (JCOG9208). Proc Am Soc Clin Oncol. 2001; 148
- 18 Roche H H, Pouillart P, Meyer N. et al . Adjuvant High Dose Chemotherapy (HDC) Improves Early Outcome for High Risk (N > 7) Breast Cancer Patients: The Pegase 01 Trial. Proc. Am. Soc. Clin Oncol. 2001; 102
- 19 Peters W P, Rosner G, Vredenburgh J, Shpall E J. et al . Updated Results Of A Prospective, Randomized Comparison Of Two Doses Of Combination Alkylating Agents (Aa) As Consolidation After Caf In High-Risk Primary Breast Cancer Involving Ten Or More Axillary Lymph Nodes (Ln): CALGB 9082/SWOG 9114/NCIC Ma-13. Proc Am Soc Clin Oncol. 2001; 81
- 20 Rodenhuis S, Bontenbal M, Beex L VAM. et al . Randomized Phase III Study of High-Dose Chemotherapy with Cyclophosphamide, Thiotepa and Carboplatin in Operable Breast Cancer with 4 or More Axillary Lymph Nodes. Proc Am Soc Clin Oncol. 2000; 286
- 21 Gianni A, Bonadonna G. Five-Year Results Of The Randomized Clinical Trial Comparing Standard Versus High-Dose Myeloablative Chemotherapy In The Adjuvant Treatment Of Breast Cancer With > 3 Positive Nodes (LN+). Proc Am Soc Clin Oncol. 2001; 80
- 22 Early Breast Cancer Trialists' Collaborative Group . Ovarian ablation in early breast cancer: Overview of the randomized trials. Lancet. 1996; 348 1189-1196
- 23 Scottish Cancer Trials Breast Group and ICRF Breast Unit, Guy's Hospital, London . Adjuvant ovarian ablation versus CMF chemotherapy in premenopausal women with pathological stage II breast carcinoma: The Scottish trial. Lancet. 1993; 341 1293-1298
- 24 Namer M. Zoladex (Goserelin) vs CMF as adjuvant therapy in pre-/perimenopausal node-positive breast cancer. Preliminary efficacy results from the ZEBRA Study (ZEBRA - Zoladex Early Breast Cancer Research Association - Trialists Group). Ann Oncol. 2000; 11 (4) 16
- 25 Wallwiener D, Possinger K, Bondar G. et al . Leuprorelin acetate vs CMF in the adjuvant treatment of premenopausal women with ER/PR-positive node-positive breast cancer: interim results of the TABLE-study. Proc Am Soc Clin Oncol. 2001; 132
- 26 Ejlertsen B, Dombernowsky P, Mouridsen H T. et al . Comparable Effect of Ovarian Ablation (OA) and CMF Chemotherapy in Premenopausal Hormone Receptor Positive Breast Cancer Patients (PRP). Proc Am Soc Clin Oncol. 1999; 18 67a
- 27 Boccardo F, Rubagotti A, Amoroso D. et al . Sequential Tamoxifen and Aminoglutethimide versus Tamoxifen alone in the adjuvant treatment of postmenopausal breast cancer patients: Results of an Italian Cooperative Study. J Clin Oncol. 2001; 19 4209-4215
- 28 Baum M. The ATAC (Arimidex, Tamoxifen, Alone or in Combination) adjuvant breast cancer trial in post-menopausal women. 24th Annual San Antonio Breast Cancer Symposium. 2001; 8
- 29 Jakesz R, Hausmaninger H, Samonigg H. et al . Comparison of adjuvant therapy with tamoxifen and goserelin vs. CMF in premenopausal stage I and II hormone-responsive breast cancer patients: Four-year results of Austrian Breast Cancer Study Group (ABCSG) Trial 5. Proc Ann Meet Soc Clin Oncol.. 1999; 18 67a
- 30 Roche H H, Kerbrat P, Bonneterre J. et al . Complete Hormonal, Blockade Versus Chemotherapy in Premenopausal Early-Stage Breast Cancer Patients (Pts) with Positive Hormone-Receptor (HR+) and 1-3 Node-Positive (N+) Tumor: Results of the FASG 06 Trial. Proc Ann Meet Soc Clin Oncol. 2000; 19 279
- 31 Davidson N, O'Neill A, Vukov A. et al . Effect of chemohormonal therapy in premenopausal, node (+), receptor (+) breast cancer: An Eastern Cooperative Oncology Group phase III intergroup trial (E5188, INT-0101). Proc Ann Meet Soc Clin Oncol. 1999; 18 67a
- 32 Fisher B, Dignam J, Wolmark N. et al . Tamoxifen and chemotherapy for lymph node-negative, estrogen receptor-positive breast cancer. J Natl Cancer Inst. 1997; 89 1673-1682
- 33 Diel I J, Solomayer E F, Costa S D. et al . Reduction in new metastases in breast cancer with adjuvant clodronate treatment. N Engl J Med. 1998; 339 357-363
- 34 Diel I J, Solomayer E F, Gollan C. et al . Bisphosphonates in the Reduction of metastases in breast cancer - Results of the extended follow-up of the first study population. Proc Am Soc Clin Oncol. 2000; 19 314
- 35 Powles T J, Paterson A HG. et al . Adjuvant clodronate reduces the incidence of bone metastases in patients with primary operable breast cancer. J Clin Oncol. 1998; 14 468
- 36 Powles T J, Paterson A H, McCloskey E, Ashley S, Tidy V A, Kania J A, Pylkkänen L. A randomised placebo controlled trial to evaluate the effect of the bisphosphonate, clodronate, on the incidence of metastases and mortality in patients with primary operable breast cancer.. Breast Cancer Res Treat. 2001; 68 (1) 1
- 37 Saarto T, Blomqvist C, Virkkunen P, Elomaa I I. Adjuvant Clodronate Treatment Does Not Reduce the Frequency of Skeletal Metastases in Node-Positive Breast Cancer Patients: 5-Year Results of a Randomized Controlled Trial. J Clin Oncol. 2001; 19 10-17
- 38 Sliwkowski M X, Lofgren J A, Lewis G D. et al . Nonclinical studies addressing the mechanism of action of trastuzumab (Herceptin). Semin Oncol. 1999; 26 60-70
- 39 Goldhirsch A, Glick J H, Gelber R D, Coates A S, Senn H J. Meeting Highlights: International Consensus Panel on the Treatment of Primary Breast Cancer. J Clin Oncol. 2001; 19 3817-3827
- 40 Eichler F, Keiling R. Survival results after 10 years of 39 patients with inflammatory breast cancer treated by two different neoadjuvant chemotherapy protocols. Bull Cancer Paris.. 1996; 83 234-238
- 41 Palangie T, Mosseri V, Mihura J. et al . Prognostic factors in inflammatory breast cancer and therapeutic implications. Eur J Cancer. 1994; 30A 921-927
-
42 Buzdar A U. et al .Proc Ann Meet. Soc Clin Oncol 1995
- 43 Cristofanilli M, Buzdar A U, Wasaff B. et al . Evaluation of paclitaxel (P) in the multimodality treatment approach of inflammatory breast cancer (IBC). The MD Andersen experience. Proc Annu Meet Soc Clin Oncol. 1998; 17 452
- 44 Antman K H. Dose-Intensive Therapy in Breast Cancer: High-Dose Cancer Therapy, Pharmacology, Hematopoietins, Stem Cells. eds: Armitage J, Antman K. Williams & Wilkins Baltimore. 1992; 42 701-713
- 45 Fisher B, Gunduz N, Saffer E. Influence of the interval between primary tumor removal and chemotherapy on kinetics and growth of metastases. Cancer Res. 1983; 43 1488
- 46 Gunduz N, Fisher B, Saffer E. Effect of surgical removal on the growth and kinetics of residual tumor. Cancer Res. 1979; 39 3861
- 47 Fisher B, Saffer E, Rudock C, Coyle J, Gunduz N. Effect of local or systemic treatment prior to primary tumor removal on the production and response to a serum growth stimulating factor in mice. Cancer Res. 1989; 49 2002
- 48 Pollak M. Growth factors and breast cancer: transformation, proliferation and metastases. 5th International Conference on Adjuvant Therapy of Primary Breast Cancer, St. Gallen 1-4.March.1995 S5
- 49 Pinedo H M, Verheul H M, D'Amato R J, Folkman J. Involvement of platelets in tumour angiogenesis?. Lancet. 1998; 352 1775-1777
- 50 Morelli D, Lazzerini D, Cazzaniga S. et al . Evaluation of the balance between angiogenic and antiangiogenic circulating factors in patients with breast and gastrointestinal cancers. Clin Cancer Res. 1998; 4 1221-1225
- 51 Goldie J H, Coldman A J. A mathematic model for relating the drug sensitivity of tumors to their spontaneous mutation rate. Cancer Treat Rep. 1979; 63 1727-1733
- 52 Sinn H P, Schmid H, Junkermann H. et al . Histologic regression of breast cancer after primary (neoadjuvant) chemotherapy. Geburtshilfe Frauenheilkd.. 1994; 54 552-558
- 53 Sinn H P. et al . Histologic regression of breast cancer after primary (neoadjuvant) chemotherapy. Geburtshilfe Frauenheilkd.. 1994; 54 552-558
- 54 Bonadonna G, Veronesi U, Brambilla C. et al . Primary chemotherapy to avoid mastectomy in tumors with diameters of three centimeters or more. J Natl Cancer Inst. 1990; 82 1539-1544
- 55 Bonadonna G, Valagussa P, Brambilla C. et al . Primary chemotherapy in operable breast cancer: eight-year experience at the Milan Cancer Institute. J Clin Oncol. 1998; 16 93-100
- 56 Fisher B, Bryant J, Wolmark N. et al . Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol. 1998; 16 2672-2685
- 57 Mauriac L, Durand M, Avril A, Dilhuydy J M. Effects of primary chemotherapy in conservative treatment of breast cancer patients with operable tumors larger than 3 cm. Results of a randomized trial in a single centre. Ann Oncol. 1991; 2 347-354
- 58 Mauriac L, MacGrogan G, Avril A. et al . Neoadjuvant chemotherapy for operable breast carcinoma larger than 3 cm: a unicentre randomized trial with a 124-month median follow-up. Institut Bergonie Bordeaux Groupe Sein (IBBGS). Ann Oncol. 1999; 10 47-52
- 59 Scholl S M, Fourquet A, Asselain B. et al . Neoadjuvant versus adjuvant chemotherapy in premenopausal patients with tumours considered too large for breast conserving surgery: preliminary results of a randomised trial: S6. Eur J Cancer. 1994; 30A (5) 645-652
- 60 Broet P, Scholl S M, de la Rochefordiere A. et al . Short and long-term effects on survival in breast cancer patients treated by primary chemotherapy: an updated analysis of a randomized trial. Breast Cancer Res Treat. 1999; 58 151-156
- 61 Semiglazov V F, Topuzov E E, Bavli J L. et al . Primary (neoadjuvant) chemotherapy and radiotherapy compared with primary radiotherapy alone in stage IIb-IIIa breast cancer. Ann Oncol. 1994; 5 591-595
- 62 Jakesz R. Comparison of pre- vs. postoperative chemotherapy in Breast Cancer Patients: Four-year results of Austrian Breast & Colorectal Cancer Study Group (ABCSD) Trial 7. Proc Ann Meet Soc Clin Oncol. 2000; 19 125
- 63 Kuerer H M, Newman L A, Ames F C. et al . Clinical course of breast cancer patients with complete pathologic primary tumor and axillary lymph node response (PCR) to doxorubicin based neoadjuvant chemotherapy. Proc Ann Meet Soc Clin Oncol. 1998; 17 451
- 64 Makris A, Powles T J, Ashley S E, Chang J, Hickish T, Tidy V A, Nash A G, Ford H T. A reduction in the requirements for mastectomy in a randomized trial of neoadjuvant chemoendocrine therapy in primary breast cancer. Ann Oncol. 1998; 9 1179-1184
- 65 Skipper H E. Kinetics of mammary tumor cell growth and implications for therapy. Cancer. 1971; 28 (6) 1479-1499
- 66 Fisher B, Brown A M, Mamounas E. et al . Effect of preoperative chemotherapy on local-regional disease in women with operable breast cancer: Findings from national surgical adjuvant breast and bowel project B18. J Clin Oncol. 1997; 15 (7) 2483-2493
- 67 Buzdar A U, Hortobagyi G N, Theriault R L. et al . Prospective randomized trial of taxol (Tax) alone versus Fluorouracil, Doxorubicin, Cyclophosphamide (FAC) as an induction therapy in patients with operable breast cancer (Br Ca). Proc Ann Meet Soc Clin Oncol. 1999; 18 273
- 68 Pouillart P, Fumoleau P, Romieu G. et al . Final results of a phase I randomized, parallel study of doxorubicin/cyclophosphamide (AC) and doxorubicin/taxol (paclitaxel) (AT) as neoadjuvant treatment of local-regional breast cancer. Proc Ann Meet Soc Clin Oncol. 1999; 18 275
- 69 Zambetti M, Mariani G, Demicheli R. et al . High Incidence of pathological complete remissions following sequential primary chemotherapy in unfavorable locally advanced breast cancer. Proc Ann Meet Soc Clin Oncol. 1999; 18 289
- 70 Hutcheon A W, Ogston K N, Heys S D. et al . Primary chemotherapy in the treatment of breast cancer: significantly enhanced clinical and pathological response with docetaxel. Proc Ann Meet Soc Clin Oncol. 2000; 19 317
- 71 Smith I E, A'Hern R P, Howell A. et al . Preoperative continuous infusional EcisF (Epirubicin, Cisplatin and infusional 5-FU) vs. conventional AC chemotherapy for early breast cancer. Proc Ann Meet Soc Clin Oncol. 2000; 19 320
- 72 Mauriac L, MacGrogan G, Avril A. et al . Neoadjuvant chemotherapy for operable breast carcinoma larger than 3 cm: a unicentre randomized trial with a 124-month median follow-up. Institut Bergonie Bordeaux Groupe Sein (IBBGS). Ann Oncol. 1999; 10 47-52
- 73 Chollet P, Bougnoux P, Amat S. et al . Induction chemotherapy in operable breast cancer: high pathological response rate induced by docetaxel. Proc Ann Meet Soc Clin Oncol. 1999; 18 297
- 74 Zambetti M, Mariani G, Demicheli R. et al . High incidence of pathological complete remissions following sequential primary chemotherapy (PC) in unfavorable locally advanced breast cancer (LABC). Proc Ann Meet Soc Clin Oncol. 1999; 18 289
- 75 Gazet J C, Ford H T, Coombes R C. et al . Prospective randomized trial of tamoxifen vs. surgery in elderly patients with breast cancer. Eur J Surg Oncol. 1994; 20 (3) 207-214
- 76 Robertson J F, Ellis I O, Elston C W. et al . Mastectomy or tamoxifen as initial therapy for operable breast cancer in elderly patients: Five-year follow-up. Eur J Cancer. 1992; 28 908-910
- 77 Mustacchi G, Milani S, Pluchinotta A. et al . Tamoxifen or surgery plus tamoxifen as primary treatment for elderly patients with operable breast cancer: The G.R.E.T.A. Trial. Group for Research on Endocrine Therapy in the Elderly. Anti-cancer Res. 1994; 14 2197-2200
- 78 Kenny F S, Robertson J FR, Ellis I O. et al . Long-term follow-up of elderly patients randomized to tamoxifen or wedge mastectomy as initial therapy for operable breast carcinoma. Breast. 1998; 7 335-339
- 79 Bates T, Riley D L, Houghton J. et al . Breast cancer in elderly women: A Cancer Research Campaign trial comparing treatment with tamoxifen and optimal surgery with tamoxifen alone. Br J Surg. 1991; 78 591-594
- 80 Mustacchi G, Latteier J, Baum M. et al . Tamoxifen alone vs. surgery plus tamoxifen for breast cancer of the elderly: Meta analysis of long-term results of the GRETA and CRC trials. Breast Cancer Res Treat. 1998; 50 227-346
- 81 Dixon J M, Love C DB, Tucker S. et al . Letrozole as primary medical therapy for locally advanced and large breast cancer. Proc Ann Meet Soc Clin Oncol. 1998; 17 400
- 82 Eiermann W, Paepke S, Appfelstaedt . et al . Preoperative treatment of postmenopausal breast cancer patients with letrozole: A randomized double-blind multicenter study. Ann Oncol. 2001; 12 1527-1532
- 83 Ellis M J, Coop A, Singh B. et al . Letrozole is more effective neoadjuvant endocrine therapy than tamoxifen for ErbB-1- and/or ErbB-2-Positive, estrogen receptor-positive primary breast cancer: Evidence from a Phase III randomised Trial. J Clin Oncol. 2001; 19 3808-3816
- 84 Ellis M J, Jaenicke F, Llombart , Cussac A. et al .Letrozole (Femara) is a more effective anti-proliferative agent than tamoxifen irrespective of ErbB1 and/or ErbB2 positive status: evidence from a phase III randomised trial of neoadjuvant endocrine therapy for postmenopausal women with estrogen receptor positive primary breast cancer. 24th Ann San Antonio Breast cancer Symposium 2001 10
- 85 Benz C C, Scott G K, Sarup J C. et al . Estrogen-dependent, tamoxifen-resistant tumorigenic growth of MCF-7 cells transfected with HER2/neu. Breast Cancer Res Treat. 1993; 24 85-95
- 86 Lee H, Jiang F, Wang Q. et al . MEKK1 activation of human estrogen receptor alpha and stimulation of the agonistic activity of 4-hydroxytamoxifen in endometrial and ovarian cells. Mol Endocrinol. 2000; 14 1882-1896
- 87 DoValle J C, Gaui M F, Salgado R. et al . Primary chemotherapy, conservative surgery & radiotherapy in breast cancer. Randomization to adjuvant chemotherapy or control in women less than 50 years. Proc Ann Meet Soc Clin Oncol. 2000; 19 485
- 88 Rodenhuis S, Richel D J, van der Wall E. et al .Randomised trial of high-dose chemotherapy and haemopoietic progenitor-cell support in operable breast cancer with extensive axillary lymph-node involvement. Lancet 1998: 515-521
- 89 Hortobagyi G N, Buzdar A U, Champlin R. et al . Proc. Lack of efficacy of adjuvant high-dose (HD) tandem chemotherapy (CT) for high-risk primary breast cancer (HRPBC) - a randomized trial. Ann Meet Soc Clin Oncol. 1998; 17 471
Dr. Peter Schmid
Medizinische Klinik mit Schwerpunkt Onkologie und Hämatologie, Charité Campus Mitte, Humboldt-Universität Berlin
Schumannstr. 20/21
10117 Berlin
Telefon: 030 450 513005
Fax: 030 450 513952
eMail: peter.schmid@charite.de