Deutsch-Schweizer Experten-Forum San Antonio, 12. Dezember 2008

Zusammenfassung

Im Rahmen des San Antonio Breast Cancer Symposiums (SABCS) haben 22 Experten aus Deutschland und der Schweiz die neuesten Studienergebnisse zur endokrinen adjuvanten Therapie des Mammakarzinoms diskutiert. Kern der Diskus­sion waren die neuen Ergebnisse der Aromatasehemmer-Studien BIG 1-98, ABCSG-8 und TEAM sowie eine Metaanalyse der klinischen Studien zur Upfront-Therapie und zur Sequenztherapie mit Aromatasehemmern. Die in San Antonio vorgestellten neuen Ergebnisse zeigen: Im Bezug auf das fernmetastasenfreie Überleben haben alle Aromatasehemmer gegenüber Tamoxifen einen eindeutigen Vorteil, der in allen vorgestellten Studien nachweislich dokumentiert ist. Jedoch gibt es möglicherweise Patientinnen, bei denen aufgrund von Komorbiditäten eine Entscheidung für Tamoxifen zu überlegen wäre. Zusammen mit der inversen Sequenz (Beginn mit Aromatasehemmer) stehen nunmehr vier Therapieoptionen zur Verfügung. Die in San Antonio 2008 vorgestellten Daten und insbesondere der Überlebensvorteil der BIG 1-98-Studie sprechen für den Beginn mit einem Aromatasehemmer. Zur Frage der optimalen Sequenz können erst weitere zu erwartende Daten endgültig Aufschluss geben.

Abstract

At the San Antonio Breast Cancer Symposium (SABCS) 22 experts from Germany and Switzerland discussed the latest study results of the ­endocrine adjuvant breast cancer therapy. The main focus was on the latest results of the aromatase inhibitor studies BIG 1-98, ABCSG-8 and TEAM as well as a meta-analysis on clinical studies analyzing upfront therapy and sequence therapy with aromatase inhibitors. The new results presented in San Antonio demonstrate: Regarding the distant disease free survival all aromatase ­inhibitors have a clear advantage compared to ­Tamoxifen which is demonstrated in all pre­sent­ed studies. However there are probably patients where a decision for Tamoxifen has to be con­sid­ered because of comorbidities. With the inverse sequence (start with aromatase inhibitor) there are now four therapy options available. The results presented in San Antonio and especially the overall survival demonstrated in the study BIG 1-98 argues for the start with an aromatase inhibitor. Concerning the question of the optimal ­sequence therapy further expected data will give more information finally.

San Antonio Breast Cancer Symposium - Aromatasehemmer - Mammakarzinom - Brustkrebs - adjuvante endokrine Therapie - BIG 1-98-Studie - ABCSG 8-Studie - TEAM-Studie - Upfront-Therapie - Sequenztherapie

San Antonio Breast Cancer Symposium - aromatase inhibitor - breast cancer - adjuvant endocrine therapy - BIG 1-98-study - ABCSG 8-study - TEAM-study - upfront therapy - sequence therapy

Literatur

• 1 Mouridsen H T, Giobbie-Hurder A, Mauriac L BIG 1–98 Collaborative Group and International Breast Cancer Study Group et al. for the . BIG 1-98: A randomized double-blind phase III study evaluating letrozole and ­tamoxifen given in sequence as adjuvant endocrine therapy for postmenopausal women with receptor-positive breast cancer.  Cancer Res. 2009;  69 (Suppl.) ,  Oral presentation SABCS 2008, Abstract # 13
• 2 Jakesz R, Gnant M, Griel R et al. Tamoxifen and anastrozole as a ­se­quencing strategy in postmenopausal women with hormone-responsive early breast cancer: updated data from the Austrian breast and colorectal cancer study group trial 8.  Cancer Res. 2009;  69 (Suppl.) ,  Oral presentation SABCS 2008, Abstract # 14
• 3 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 ,  Oral presentation SABCS 2008, Abstract # 15
• 4 Ingle J N, Dowsett M, Cuzick J et al. Aromatase inhibitors vs tamoxifen as adjuvant therapy for postmenopausal women with estrogen receptor positive breast cancer: meta-analysis of randomized trials of monotherapy and switching strategies.  Cancer Res. 2009;  69 (Suppl.) ,  Oral presentation SABCS 2008, Abstract # 12
• 5 Thürlimann B, Keshaviah A, Coates A S The Breast International Group (BIG) 1-98 Collaborative Group et al.,. A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer.  N Engl J Med. 2005;  353 2747-2757
• 6 Coates A S, Keshaviah A, Thurlimann B et al. Five years of letrozole compared with tamoxifen as initial adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer: update of study BIG 1-98.  J Clin Oncol. 2007;  25 486-492
• 7 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.  Oral presentation SABCS. 2008;  Abstract # 15 a
• 8 Ingle J N, Dowsett M, Cuzick J et al. Aromatase inhibitors versus tamoxifen as adjuvant therapy for postmenopausal women with estrogen ­receptor positive breast cancer: meta-analyses of randomized trials of monotherapy and switching strategies.  Oral presentation SABCS. 2008;  Abstract # 12 a
• 9 Johnston S, Pegram M, Press M et al. Lapatinib combined with letrozole vs. letrozole alone for front line postmenopausal hormone receptor positive (HR +) metastatic breast cancer (MBC): first results from the EGF30008 Trial.  Oral presentation SABCS. 2008;  Abstract # 46 a
• 10 Johnston S, Pegram M, Press M et al. First-line therapy with lapatinib combined with letrozole vs letrozole alone for postmenopausal hormone receptor positive MBC: first results from the phase III double-blind EGF30008 trial.  Cancer Res. 2009;  69 (Suppl.) 46
• 11 Howell A, Cuzick J, Baum M ATAC Trialists’ Group et al. Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years’ adjuvant treatment for breast cancer.  Lancet. 2005;  365 60-62
• 12 Sestak I, Cuzick J, Sapunar F et al. Risk factors for joint symptoms in ­patients enrolled in the ATAC trial: a retrospective, exploratory analysis.  Lancet Oncol. 2008;  9 866-872
• 13 Baum M, Budzar A U, Cuzick J The ATAC (Arimidex,Tamoxifen, Alone or in Combination) Trialists’ Group et al.,. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomized trial.  Lancet. 2002;  359 2131-2139
• 14 Hanrahan E O, Gonzalez-Angulo A M, Giordano S H et al. Overall survival and cause-specific mortality of patients with stage T1a,bN0M0 breast carcinoma.  J Clin Oncol. 2007;  25 4952-4960
• 15 Glück S. The prevention and management of distant metastases in women with breast cancer.  Cancer Invest. 2007;  25 6-13
• 16 Del Mastro L, Clavarezza M, Venturini M. Reducing the risk of distant metastases in breast cancer patients: role of aromatase inhibitors.  Cancer Treat Rev. 2007;  33 681-687
• 17 Mauriac L, Keshaviah A, Debled M BIG 1-98 Collaborative Group; International Breast Cancer Study Group et al.,. Predictors of early relapse in postmenopausal women with hormone receptor-positive breast cancer in the BIG 1-98 trial.  Ann Oncol. 2007;  18 859-867
• 18 Houghton J et al. Ann Oncol. 2006;  17 (suppl 9) Abstract 243PD ix94
• 19 Goss P E, Ingle J N, Martino S et al. A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer.  N Engl J Med. 2003;  349 1793-1802
• 20 Goss P E, Ingle J N, Martino S et al. Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: updated findings from NCIC CTG MA 17.  J Natl Cancer Inst. 2005;  97 1262-1271
• 21 ATAC Trialists’Group . Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years’adjuvant treatment for breast cancer.  Lancet. 2005;  365 60-62
• 22 Perez E A, Josse R Q, Pritchard K I et al. Effect of letrozole versus placebo on bone mineral density in women completing ≥ 5 years (yrs) of adjuvant tamoxifen: NCIC CTG MA 17 b.  Breast Cancer Res Treat. 2004;  88 36
• 23 Coleman R E, Banks L M, Girgis S I Intergroup Exemestane Study group et al.,. Skeletal effects of exemestane on bone-mineral density, bone biomarkers, and fracture incidence in postmenopausal women with early breast cancer participating in the Intergroup Exemestane Study (IES): a randomised controlled study.  Lancet Oncol. 2007;  8 119-127
• 24 Hillner B E, Ingle J N, Chlebowski R T et al. American Society of Clinical Oncology 2003 update of the role of bisphosphonates and bone health issues in women with breast cancer.  J Clin Oncol. 2003;  21 4042-4057
• 25 Hadji P et al. Annals of Oncology. 2008;  ,  Epub ahead of print; 2008
• 26 Coombes R C, Kilburn L S, Snowdon C F Intergroup Exemestane Study et al.,. Survival and safety of exemestane versus tamoxifen after 2–3 years’ tamoxifen treatment (Intergroup Exemestane Study): a ran­domised controlled trial.  Lancet. 2007;  369 559-570
• 27 Cuzick J et al. Breast Cancer Res Treat. 2006;  100 (abstract 104)
• 28 Coombes R C, Kilburn L S, Snowdon C F Intergroup Exemestane Study et al. A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer.  N Engl J Med. 2004;  350 1081-1092
• 29 Jakesz R, Jonat W, Gnant M et al. Switching ofpostmenopausal women with endocrine-responsive early breast cancer to anastrozole after 2 years’ adjuvant tamoxifen: combined results of ABCSG trial 8 and ARNO95 trial.  Lancet. 2005;  366 455-462