Geburtshilfe Frauenheilkd 2010; 70(3): 177-183
DOI: 10.1055/s-0029-1240912
Übersicht

© Georg Thieme Verlag KG Stuttgart · New York

Kongressbericht vom 32. Annual San Antonio Breast Cancer Symposium vom 10.–13.12.2009

„Ein internationales wissenschaftliches Symposium mit dem Ziel der Interaktion und des Gedankenaustausches zu Fragen des Brustkrebses zwischen Forschern und Klinikern“Report of the 32nd Annual San Antonio Breast Cancer Symposium, December 10–13, 2009“An International Scientific Symposium for Interaction and Exchange Among Basic Scientists and Clinicians in Breast Cancer”E. Ruckhäberle1 , A. Rody1 , M. Kaufmann1
  • 1Klinik für Gynäkologie und Geburtshilfe der J. W. Goethe-Universität, Frankfurt
Further Information

Publication History

eingereicht 28.1.2010

akzeptiert 29.1.2010

Publication Date:
04 March 2010 (online)

Zusammenfassung

Das letztjährige San Antonio Breast Cancer Symposium wurde dominiert von den molekularen Grundlagen des Mammakarzinoms und den sich daraus ergebenden diagnostischen und v. a. therapeutischen Möglichkeiten. Während in der endokrinen Therapie keine wegweisend neuen Resultate vorgestellt wurden, dominierte die zielgerichtete Therapie in ihren vielseitigen Facetten deutlich das Kongressgeschehen. Wie auch in den vergangenen Jahren wurden zu gleichen Teilen Ergebnisse aus der Grundlagenforschung und Präklinik sowie von klinischen Studien vorgestellt und diskutiert. Im Bereich der antihormonellen Therapie der postmenopausalen Patientin zeigte sich in der 5-Jahres-Analyse der TEAM-Studie eine Äquieffektivität für die sequenzielle Therapie und die Upfront-Therapie mit Exemestan. Auch im Langzeit-Follow-up der IES-Studie bleibt die Überlegenheit des Switch auf Exemestan nach 2–3 Jahren Tamoxifen hinsichtlich der Prognose erhalten. Die erweiterte adjuvante Therapie ist für Frauen, die bei Erstdiagnose noch prämenopausal waren, von besonderer prognostischer Bedeutung. Dieser Effekt bleibt auch bei einem Beginn der erweiterten adjuvanten Therapie bis zu 6 Jahre nach Ende der Tamoxifeneinnahme erhalten. In der metastasierten Situation lässt sich durch die dauerhafte Einnahme von 500 mg Fulvestrant nur ein marginaler Benefit erreichen, die Kombination aus Fulvestrant und Anastrozol ist der Anastrozolmonotherapie nicht überlegen. Im Bereich der Knochengesundheit stand die Frage der prognostischen Bedeutung einer Bisphosphonattherapie im Vordergrund. Ein 2. Schwerpunkt war Denosumab, welches als monoklonaler Antikörper gegen RANK-Ligand eine höhere Wirksamkeit gegen Knochenmetastasen aufweist als die klassische Zoledronsäure. Im Bereich der zielgerichteten Therapien konnte der Wert einer Trastuzumabtherapie in der Adjuvanz unterstrichen werden. Dabei zeigte die gleichzeitige Verabreichung von Trastuzumab mit der taxanhaltigen Chemotherapie die besten Ergebnisse. Bei metastasierten Patienten unterstrichen neue Studienergebnisse den Wert einer Kombination aus Trastuzumab und Lapatinib und erhärteten die positiven Resultate der anfänglich bereits im vergangenen Jahr vorgestellten neuen Substanzen wie Neratinib und T‐DM1. Bei Her-2/neu-negativen Karzinomen etabliert sich Bevacizumab weiter als Kombinationspartner in vielfältigen Kombinationen. Neue Multityrosinkinasehemmer konnten im Falle von Motesanib und Sunitinib noch nicht überzeugen, während Sorafenib in Kombination mit Chemotherapie eine gute Effektivität besitzt. Alle diese neuen Tyrosinkinasehemmer haben gemein, dass sie ein frühes, gezieltes und konsequentes Nebenwirkungsmanagement unerlässlich machen.

Abstract

The molecular basics of breast cancer and the resulting diagnostic and therapeutic opportunities dominated last year's annual San Antonio Breast Cancer meeting. Even though no breakthroughs in endocrine therapy were presented, the many facets of targeted therapies took center stage in the conference program. As in previous years, basic research, preclinical and clinical studies were presented. In the field of endocrine therapy the 5-year follow-up analysis of the TEAM trial demonstrated equal efficacy of exemestane upfront or as a sequential therapy after 2 years of tamoxifen. Moreover, a switch to exemestane was confirmed to be superior according to the DFS and for overall survival in the long-term follow-up of the IES study compared to 5 years of tamoxifen. The results of the MA 27 trial demonstrated the high prognostic impact of extended adjuvant therapy, especially in premenopausal woman (at the time of primary diagnosis). This effect remains constant even if therapy is initiated up to 6 years after primary adjuvant therapy. In metastatic breast cancer 500 mg fulvestrant was found to provide a marginal prognostic benefit to women. A combination of fulvestrant and anastrozole just missed showing a higher efficacy than anastrozole monotherapy. With regard to bone health, priority was given to the prognostic impact of bisphosphonates and denosumab. The latter is a monoclonal antibody against RANK ligand and shows a superior efficacy to zoledronate in terms of pain relief and treatment of bone metastases. The value of adjuvant trastuzumab treatment was underlined by means of targeted therapies and concurrent treatment with taxane chemotherapy demonstrated the highest efficacy. In metastatic breast cancer a combination of trastuzumab and lapatinib was superior to monotherapy. Recent promising results of new EGF-receptor targeting drugs such as neratinib and T-DM1 confirmed the interesting data presented at an earlier meeting last year. In Her 2neu negative breast cancer, bevacizumab was demonstrated to be a good combination partner not only for taxanes but for capecitabine and gemcitabine as well. While some of the new multityrosine kinase inhibitors did not provide convincing results, others like sorafenib did demonstrate a good efficacy in combination with paclitaxel and capecitabine. All these tyrosine kinase inhibitors demand early and consequent prevention or treatment of associated side effects.

Literatur

  • 1 Regan M M, Colleoni M, Giobbie-Hurder A et al. Adjusting for selective crossover in analyses of letrozole (Let) versus tamoxifen (Tam) in the BIG 1-98 trial.  Cancer Res. 2009;  69 (Suppl.) 2-Abstract 12
  • 2 Jones S E, Seynaeve C, Hasenburg A et al. Results of the first planned analysis of the TEAM (tamoxifen exemestane adjuvant multinational) prospective randomized phase III trial in hormone sensitive postmenopausal early breast cancer.  Cancer Res. 2009;  69 (Suppl.) 2-Abstract 15
  • 3 Rea D, Hasenburg A, Seynaeve C et al. Five years of exemestane as initial therapy compared to 5 years of tamoxifen followed by exemestane: The TEAM trial, a prospective, randomized, phase III trial in postmenopausal women with hormone-sensitive early breast cancer.  Cancer Res. 2009;  69 (S3) Abstract 11
  • 4 Bliss J M, Kilburn L S, Coleman R E IES Steering Committee et al., on behalf of the . Disease related outcome with long term follow-up: An updated analysis of the Intergroup Exemestane Study (IES).  Cancer Res. 2009;  69 (S3) Abstract 12
  • 5 Goetz M P, Berry D A, Klein T E. International Tamoxifen Pharmacogenomics Consortium . Adjuvant tamoxifen treatment outcome according to cytochrome P450 2D6 (CYP2D6) phenotype in early stage breast cancer: findings from the International Tamoxifen Pharmacogenomics Consortium.  Cancer Res. 2009;  69 (S3) Abstract 33
  • 6 Goss P E, Ingle J N, Martino S et al. Outcomes of women who were premenopausal at diagnosis of early stage breast cancer in the NCIC CTG MA17 trial.  Cancer Res. 2009;  69 (S3) Abstract 13
  • 7 Cuzick J, Sestak I, Pinder S E et al. Beneficial effect of tamoxifen for women with DCIS: long-term results from the UK/ANZ DCIS trial in women with locally excised DCIS.  Cancer Res. 2009;  69 (S3) Abstract 34
  • 8 Bergh J, Jönsson P E, Lidbrink E et al. First results from FACT – an open-label, randomized phase III study investigating loading dose of fulvestrant combined with anastrozole versus anastrozole at first relapse in hormone receptor positive breast cancer.  Cancer Res. 2009;  69 (S3) Abstract 23
  • 9 Stopeck A, de Boer R, Fujiwara Y et al. A comparison of denosumab versus zoledronic acid for the prevention of skeletal-related events in breast cancer patients with bone metastases.  Cancer Res. 2009;  69 (S3) Abstract 22
  • 10 Brufsky A, Harker G, Beck J T et al. The effect of zoledronic acid on aromatase inhibitor-associated bone loss in postmenopausal women with early breast cancer receiving adjuvant letrozole: The Z-FAST study 5-year final follow-up.  Cancer Res. 2009;  69 (S3) Abstract 4083
  • 11 Coleman R, Bundred N, De Boer R et al. Impact of zoledronic acid in postmenopausal women with early breast cancer receiving adjuvant letrozole: Z-FAST, ZO-FAST, and E-ZO-FAST.  Cancer Res. 2009;  69 (S3) Abstract 4082
  • 12 Chlebowski R T, Chen Z, Cauley J A et al. Oral bisphosphonate and breast cancer: prospective results from the Women's Health Initiative (WHI).  Cancer Res. 2009;  69 (S3) Abstract 21
  • 13 Rennert G, Pinchev M, Rennert H S. Use of bisphosphonates and risk of postmenopausal breast cancer.  Cancer Res. 2009;  69 (S3) Abstract 27
  • 14 Bundred N J, Cramer A, Morris J et al. Randomised placebo controlled trial studying short term biological effects of the combination of letrozole and zoledronic acid on invasive breast cancer.  Cancer Res. 2009;  69 (S3) Abstract 2009
  • 15 Perez E A, Suman V J, Davidson N E et al. Results of chemotherapy alone, with sequential or concurrent addition of 52 weeks of trastuzumab in the NCCTG N9831 HER2-positive adjuvant breast cancer trial.  Cancer Res. 2009;  69 (S3) Abstract 80
  • 16 Slamon D, Eiermann W, Robert N BCIRG006 Investigators et al., on behalf of . Phase III randomized trial comparing doxorubicin and cyclophosphamide followed by docetaxel (AC→T) with doxorubicin and cyclophosphamide followed by docetaxel and trastuzumab (AC→TH) with docetaxel, carboplatin and trastuzumab (TCH) in Her2neu positive early breast cancer patients: BCIRG 006 study.  Cancer Res. 2009;  69 (S3) Abstract 62
  • 17 von Minckwitz G, Bauerfeind I, Gerber B et al. Geparquinto: First planned safety analysis on 60 patients with HER2 negative primary breast cancer receiving neoadjuvant chemotherapy ± bevacizumab or ± RAD001 (GBG 44).  Cancer Res. 2009;  69 (S3) Abstract 1096
  • 18 Sellers W. The development of PI3K pathway modulators for cancer.  Cancer Res. 2009;  69 (S3) Abstract P-2-1
  • 19 Weinberg R A. Breast cancer stem cells and the epithelial-mesenchymal transition.  Cancer Res. 2009;  69 (S3) Abstract A 1-1
  • 20 Blackwell K L, Burstein H J, Sledge G W et al. Updated survival analysis of a randomized study of lapatinib alone or in combination with trastuzumab in women with HER2-positive metastatic breast cancer progressing on trastuzumab therapy.  Cancer Res. 2009;  69 (S3) Abstract 61
  • 21 Huober J, Fasching P, Paepke S et al. Letrozole in combination with trastuzumab is superior to letrozole monotherapy as first line treatment in patients with hormone-receptor-positive, HER2-positive metastatic breast cancer (MBC) – results of the eLEcTRA trial.  Cancer Res. 2009;  69 (S3) Abstract 4094
  • 22 Vukelja S, Rugo H, Vogel C et al. A phase II study of trastuzumab-DM1, a first-in-class HER2 antibody-drug conjugate, in patients with HER2+ metastatic breast cancer.  Cancer Res. 2009;  69 (Suppl.) 2-Abstr. Nr. 33
  • 23 Krop I, LoRusso P, Miller K D et al. A phase II study of trastuzumab-DM1 (T-DM1), a novel HER2 antibody-drug conjugate, in patients previously treated with lapatinib, trastuzumab, and chemotherapy.  Cancer Res. 2009;  69 (S3) Abstract 710
  • 24 Burstein H J, Sun Y, Tan A R et al. Neratinib (HKI-272), an irreversible pan erbB receptor tyrosine kinase inhibitor: phase 2 results in patients with advanced HER2+ breast cancer.  Cancer Res. 2009;  69 (Suppl. 2) Abstract 37
  • 25 Burstein H J, Sun Y, Dirix L et al. Gastrointestinal and cardiovascular safety profiles of neratinib monotherapy in patients with advanced ErbB2-positive breast cancer.  Cancer Res. 2009;  69 (S3) Abstract 5096
  • 26 Chow L, Gupta S, Hershman D et al. Safety and efficacy of neratinib (HKI-272) in combination with paclitaxel in ErbB2+ metastatic breast cancer.  Cancer Res. 2009;  69 (S3) Abstract 5081
  • 27 Saura C, Martin M, Moroose R et al. Safety of neratinib (HKI-272) in combination with capecitabine in patients with solid tumors: a phase 1/2 study.  Cancer Res. 2009;  69 (S3) Abstract 5108
  • 28 Miles D W, Chan A, Romieu G The BO17708 Study Group et al. Final overall survival (OS) results from the randomised, double-blind, placebo-controlled, phase III AVADO study of bevacizumab (BV) plus docetaxel (D) compared with placebo (PL) plus D for the first-line treatment of locally recurrent (LR) or metastatic breast cancer (mBC).  Cancer Res. 2009;  69 (S3) Abstract 41
  • 29 Brufsky A, Bondarenko I N, Smirnov V et al. RIBBON-2: A randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of HER2-negative metastatic breast cancer.  Cancer Res. 2009;  69 (S3) Abstract 42
  • 30 Geberth M, Foerster F, Klare P et al. Efficacy and safety of first-line bevacizumab (BEV) combined with paclitaxel (PAC) according to age: subpopulation analysis of a large, multicenter, non-interventional study in patients (Pts) with HER2-negative metastatic breast cancer (MBC).  Cancer Res. 2009;  69 (S3) Abstract 6085
  • 31 Guarneri V, Miles D, Robert N J et al. Analysis of bevacizumab (Bev) therapy, bisphosphonate use and osteonecrosis of the jaw (ONJ) in > 1900 patients treated in two randomized, controlled trials.  Cancer Res. 2009;  69 (S3) Abstract 208
  • 32 Barrios C, Liu M-C, Lee S C et al. Phase III randomized trial of sunitinib (SU) vs. capecitabine (C) in patients (Pts) with previously treated HER2-negative advanced breast cancer (ABC).  Cancer Res. 2009;  69 (S3) Abstract 46
  • 33 Mackey J, Hurvitz S, Crown J et al. CIRG/TORI 010: 10-month analysis of a randomized phase II trial of motesanib plus weekly paclitaxel as first line therapy in HER2-negative metastatic breast cancer (MBC).  Cancer Res. 2009;  69 (S3) Abstract 47
  • 34 Baselga J, Roché H, Costa F Grupo Español de Estudio Tratamiento y Otras Estrategias Experimentales en Tumores Só lidos et al. SOLTI-0701: A multinational double-blind, randomized phase 2b study evaluating the efficacy and safety of sorafenib compared to placebo when administered in combination with capecitabine in patients with locally advanced or metastatic breast cancer (BC).  Cancer Res. 2009;  69 (S3) Abstract 45
  • 35 Gradishar W J, Kaklamani V, Prasad Sahoo T et al. A double-blind, randomized, placebo-controlled, phase 2b study evaluating the efficacy and safety of sorafenib (SOR) in combination with paclitaxel (PAC) as a first-line therapy in patients (pts) with locally recurrent or metastatic breast cancer (BC).  Cancer Res. 2009;  69 (S3) Abstract 44
  • 36 Isaacs C, Wilkinson M, Liu M C et al. Phase II study of sorafenib with anastrozole to overcome resistance to aromatase inhibitors (AIs) in patients with hormone receptor positive (ER/PR+) AI resistant metastatic breast cancer (MBC).  Cancer Res. 2009;  69 (S3) Abstract 3090
  • 37 O'Shaughnessy J, Osborne C, Pippen J et al. Final results of a randomized phase II study demonstrating efficacy and safety of BSI-201, a poly (ADP-ribose) polymerase (PARP) inhibitor, in combination with gemcitabine/carboplatin (G/C) in metastatic triple negative breast cancer (TNBC).  Cancer Res. 2009;  69 (S3) Abstract 3122
  • 38 O'Shaughnessy J, Osborne C, Pippen J et al. Efficacy of BSI-201, a poly (ADP-ribose) polymerase-1 (PARP1) inhibitor, in combination with gemcitabine/carboplatin in patients with metastatic triple-negative breast cancer: results of a randomized phase II-trial.  J Clin Oncol. 2009;  27 18s-(Suppl.; abstract 3)

Dr. Eugen Ruckhäberle

Klinik für Gynäkologie und Geburtshilfe
J. W. Goethe-Universität

Theodor-Stern-Kai 7

60590 Frankfurt

Email: eugen.ruckhaeberle@med.uni-frankfurt.de

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