Aktuelles vom San Antonio Breast Cancer Symposium 2011

Transkript

1 Aktuelles vom San Antonio Breast Cancer Symposium 2011 Was ist wichtig für die Klinik? Brustzentrum Prof. Harbeck

2 CAMPUS INNENSTADT UND GROSSHADERN KLNIK UND POLIKLINIK FÜR FRAUENHEILKUNDE UND GEBURTSHILFE San Antonio 2011 was war wichtig? Frühes Mammakarzinom: Operatives Vorgehen Axilla (Prof. Janni) Biomarker (neo-) adjuvante Chemotherapie Bisphosphonate (Prof. Hadji) Zwei neue zielgerichtete Optionen: Pertuzumab (HER2 positiv) Everolimus (HR positiv) Persönliches Fazit München, 21/01/12 Prof. Harbeck Wintersymposium

3 CAMPUS INNENSTADT UND GROSSHADERN KLNIK UND POLIKLINIK FÜR FRAUENHEILKUNDE UND GEBURTSHILFE 22 Presseerklärungen Förderpreis für deutsche Nachwuchswissenschaftlerin München, 21/01/12 Prof. Harbeck Wintersymposium 3

5 CAMPUS INNENSTADT UND GROSSHADERN KLNIK UND POLIKLINIK FÜR FRAUENHEILKUNDE UND GEBURTSHILFE München, 21/01/12 Prof. Harbeck Wintersymposium 5

10 CAMPUS INNENSTADT UND GROSSHADERN KLNIK UND POLIKLINIK FÜR FRAUENHEILKUNDE UND GEBURTSHILFE San Antonio 2011 Adjuvante Chemotherapie GAIN Studie (Möbus): noch keine Überlebensdaten ADEBAR Studie (Janni): EC-Doc äquieffektiv vgl. mit CE 120 F bei besserer Verträglichkeit PlanB Studie (Nitz): 6 Todesfälle (5 TC, 1 EC-Doc) ARAplus Studie (Nitz): Darbepoetin stabilisiert Hb ohne negative Auswirkung auf Überleben München, 21/01/12 Prof. Harbeck Wintersymposium 10

12 planb trial: Design HER2-negative primary breast cancer pt1-4 free margins pn+ pn0 high risk pt>2cm G2-3 upa/pai-1 HR- age <35 years HR- HR+ R E C U R R E N C E S C O R E 0-3 LN and RS>11 or >/= 4 LN 0-3 LN and RS<11 R A N D O M I Z A T I O N T 75 C 600 x 6* E 90 C 600 x4 Doc 100 x4* Endocrine therapy* * endocrine therapy and RT according to national guidelines

13 planb trial: Recruitment Feb 09 Apr 09 Jun 09 Aug 09 Oct 09 Dec 09 Feb 10 Apr 10 Jun 10 Aug 10 Oct 10 Dec 10 Feb 11 Apr 11 Jun 11 Aug 11 0 Registration Randomization Reg (total) Rando (total) 3196 registered und 2448 randomized patients from 91 study sites 13

14 Shared decision making according to Recurrence Score in planb trial planb cutoffs 18% 60% 22% 18% of patients potentially spared chemotherapy 88% acceptance Dropout rates high risk: n=45, 8.2% intermediate risk: n=249, 16.1% N0 patients with RS % low risk: n=19, 4.1%

15 Recurrence score by upa/pai-1 Concordance is limited If the RS is high, it is quite likely that upa/pai-1 is high However, the converse is not true 2% 4% 41% 74% 57% 22% 11% 20% 42% 64% 47% 16% high risk (>25) intermediate risk (12-25) low risk (0-11) low upa/pai-1 high 15

16 planb trial risk assessment: Conclusions I Adjuvant chemotherapy could be spared in about 20% of HR+ patients on the basis of their excellent prognosis as identified by RS <12. Routine risk assessment by Recurrence Score feasible: High compliance of patients / physicians with Oncotype DX results. Risk concordance: high RS usually implies high risk by Central G3 luminal B subtype (HR+, Ki-67 high) high upa/pai-1 Risk assessment within low and intermediate RS risk groups exhibits substantial heterogeneity according to central grade, luminal subtype, and upa/pai-1. 16

17 WSG-ADAPT trial: HR+ sub-protocol High risk Chemotherapy Prognosis Efficacy Low proliferation response (RS, Ki-67) Endocrine therapy 3 weeks (RS, Ki-67) Intermediate risk Good proliferation response Core Biopsy Core Biopsy/ Surgery Low risk Endocrine therapy PIs: N. Harbeck; U. Nitz 17

18 CAMPUS INNENSTADT UND GROSSHADERN KLNIK UND POLIKLINIK FÜR FRAUENHEILKUNDE UND GEBURTSHILFE San Antonio 2011 Biomarker DCIS Signatur (GHI): ECOG E5194 (keine Radiatio) basiert auf recurrence score (ER, proliferation) PAMM 50 Test (Dowsett): Paraffingewebe TransATAC intrische Subtypen, Risk of Recurrence (ROR) Informationen zusätzlich zu recurrence score München, 21/01/12 Prof. Harbeck Wintersymposium 18

21 San Antonio Breast Cancer Symposium Cancer Therapy and Research Center at UT Health Science Center December 6-10, 2011 A Phase III, Randomized, Double-Blind, Placebo- Controlled Registration Trial to Evaluate the Efficacy and Safety of Placebo + Trastuzumab + Docetaxel vs. Pertuzumab + Trastuzumab + Docetaxel in Patients with Previously Untreated HER2-Positive Metastatic Breast Cancer (CLEOPATRA) J Baselga, 1 S-B Kim, 2 S-A Im, 3 R Hegg, 4 Y-H Im, 5 L Roman, 6 J L Pedrini, 7 J Cortés, 8 A Knott, 9 E Clark, 9 G Ross 9 and S M Swain 10 1 Massachusetts General Hospital Cancer Center, Boston, MA, USA; 2 Department of Oncology, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Korea; 3 Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea; 4 Hospital Pérola Byington, São Paulo, Brazil; 5 Division of Hematology and Medical Oncology, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; 6 Leningrad Regional Oncology Dispensary, St Petersburg, Russian Federation; 7 CPMEC-Mastology Unit of Conceição Hospital, Porto Alegre, Brazil; 8 Department of Oncology, Vall d Hebron University Hospital, Barcelona, Spain; 9 Roche Products Limited, Welwyn, UK; 10 Washington Cancer Institute, Washington Hospital Center, Washington D.C., USA Copyrights for this presentation are held by the author/presenter. Contact them at JBASELGA@PARTNERS.ORG for permission to reprint and/or distribute.

22 Study design San Antonio Breast Cancer Symposium Cancer Therapy and Research Center at UT Health Science Center December 6-10, 2011 n=406 Placebo + trastuzumab PD Patients with HER2-positive MBC centrally confirmed (N = 808) 1:1 Docetaxel* 6 cycles recommended Pertuzumab + trastuzumab PD n=402 Docetaxel* 6 cycles recommended Randomization was stratified by geographic region and prior treatment status (neo/adjuvant chemotherapy received or not) Study dosing q3w: Pertuzumab/Placebo: 840 mg loading dose, 420 mg maintenance Trastuzumab: 8 mg/kg loading dose, 6 mg/kg maintenance Docetaxel: 75 mg/m 2, escalating to 100 mg/m 2 if tolerated * <6 cycles allowed for unacceptable toxicity or PD; >6 cycles allowed at investigator discretion MBC, metastatic breast cancer; PD, progressive disease Copyrights for this presentation are held by the author/presenter. Contact them at JBASELGA@PARTNERS.ORG for permission to reprint and/or distribute. 22

23 San Antonio Breast Cancer Symposium Cancer Therapy and Research Center at UT Health Science Center December 6-10, 2011 Primary endpoint: Independently assessed PFS n = 433 PFS events Progression-free survival (%) n at risk Ptz + T + D Pla + T + D D, docetaxel; PFS, progression-free survival; Pla, placebo; Ptz, pertuzumab; T, trastuzumab Ptz + T + D: median 18.5 months Pla + T + D: median 12.4 months Time (months) = 6.1 months HR = % CI p< Stratified by prior treatment status and region Copyrights for this presentation are held by the author/presenter. Contact them at JBASELGA@PARTNERS.ORG for permission to reprint and/or distribute. 23

24 San Antonio Breast Cancer Symposium Cancer Therapy and Research Center at UT Health Science Center December 6-10, 2011 Independently assessed PFS in predefined subgroups Favors pertuzumab Favors placebo n HR 95% CI Prior (neo)adjuvant chemotherapy Region Age group Race All No Yes Europe North America South America Asia <65 years 65 years <75 years 75 years White Black Asian Other Disease type ER/PgR status HER2 status Visceral disease Non-visceral disease Positive Negative Unknown IHC 3+ FISH-positive Unstratified analyses ER, estrogen receptor; IHC, immunohistochemistry; FISH, fluorescence in situ hybridization; PgR, progesterone receptor; PFS, progression-free survival Copyrights for this presentation are held by the author/presenter. Contact them at JBASELGA@PARTNERS.ORG for permission to reprint and/or distribute. 24

25 San Antonio Breast Cancer Symposium Cancer Therapy and Research Center at UT Health Science Center December 6-10, 2011 Independently assessed PFS by prior trastuzumab therapy in patients with (neo)adjuvant therapy Prior (neo)adjuvant trastuzumab treatment (n = 88) No prior (neo)adjuvant trastuzumab treatment (n = 288) Placebo + trastuzumab + docetaxel Median PFS, months Pertuzumab + trastuzumab + docetaxel Median PFS, months Hazard ratio (CI) 0.62 ( ) 0.60 ( ) PFS, progression-free survival Copyrights for this presentation are held by the author/presenter. Contact them at JBASELGA@PARTNERS.ORG for permission to reprint and/or distribute. 25

26 San Antonio Breast Cancer Symposium Cancer Therapy and Research Center at UT Health Science Center December 6-10, 2011 Overall survival: Predefined interim analysis Median follow-up: 19.3 months, n = 165 OS events Overall survival (%) Ptz + T + D: 69 events Pla + T + D: 96 events HR = 0.64* 95% CI p = * n at risk Time (months) Pertuzumab + T + D Placebo + T + D * The interim OS analysis did not cross the pre-specified O Brien-Fleming stopping boundary (HR 0.603; p ) D, docetaxel; OS, overall survival; Pla, placebo; Ptz, pertuzumab; T, trastuzumab Copyrights for this presentation are held by the author/presenter. Contact them at JBASELGA@PARTNERS.ORG for permission to reprint and/or distribute. 26

27 San Antonio Breast Cancer Symposium Cancer Therapy and Research Center at UT Health Science Center December 6-10, 2011 Summary and conclusions CLEOPATRA met its primary endpoint and demonstrated a statistically significant and clinically meaningful improvement in PFS (HR = 0.62) in patients with HER2-positive MBC Median PFS increased by 6.1 months from 12.4 to 18.5 months The PFS improvement was consistent across subgroups and supported by the secondary endpoints of ORR and OS (immature) The combination of pertuzumab and trastuzumab plus docetaxel increased rates of diarrhea, rash, mucosal inflammation, febrile neutropenia, and dry skin These adverse events were primarily grades 1 2, manageable, and occurred during docetaxel therapy There was no increase in cardiac adverse events or LVSD This new regimen may be practice-changing in HER2-positive first-line MBC Copyrights for this presentation are held by the author/presenter. Contact them at JBASELGA@PARTNERS.ORG for permission to reprint and/or distribute. 27

28 San Antonio Breast Cancer Symposium Cancer Therapy and Research Center at UT Health Science Center December 6 10, 2011 TRYPHAENA: Study design HER2-positive EBC centrally confirmed (n = 225) A B C Cycles FEC Docetaxel Pertuzumab + trastuzumab FEC Docetaxel Docetaxel Pertuzumab + trastuzumab Pertuzumab + trastuzumab S u r g e r y Trastuzumab to complete 1 year All 3 arms were experimental Carboplatin Study dosing q3w: FEC: 500 mg/m 2, 100 mg/m 2, 600 mg/m 2 Carboplatin: AUC 6 Trastuzumab: 8 mg/kg loading dose, 6 mg/kg maintenance Pertuzumab: 840 mg loading dose, 420 mg maintenance Docetaxel: 75 mg/m 2 (escalating to 100 mg/m 2 if tolerated, in Arms A and B only) AUC, area under the plasma concentration-time curve; EBC, early breast cancer; FEC, 5-fluorouracil, epirubicin, cyclophosphamide Copyrights for this presentation are held by the author/presenter. Contact them at Andreas.Schneeweiss@med.uni-heidelberg.de for permission to reprint and/or distribute. 28

29 San Antonio Breast Cancer Symposium Cancer Therapy and Research Center at UT Health Science Center December 6 10, 2011 TRYPHAENA: Cardiac events during neoadjuvant treatment FEC+H+P x3 T+H+P x3 n = 72 FEC x3 T+H+P x3 n = 75 TCH+P x6 n = 76 Symptomatic LVSD (grade 3), n (%) 0 (0.0) 2 (2.7) 0 (0.0) LVSD (all grades), n (%) 4 (5.6) 3 (4.0) 2 (2.6) LVEF decline 10% points and below 50%, n (%) 3 (4.2) 4 (5.3) 3 (3.9) FEC, 5-fluorouracil, epirubicin, cyclophosphamide; H, trastuzumab; LVEF, left ventricular ejection fraction; LVSD, left ventricular systolic dysfunction; P, pertuzumab; T, docetaxel; TCH, docetaxel/carboplatin/trastuzumab Copyrights for this presentation are held by the author/presenter. Contact them at Andreas.Schneeweiss@med.uni-heidelberg.de for permission to reprint and/or distribute. 29

30 San Antonio Breast Cancer Symposium Cancer Therapy and Research Center at UT Health Science Center December 6 10, 2011 TRYPHAENA: Pathologic complete response ypt0/is ypt0 ypn0 Pathologic complete response (%) FEC+H+P x3 T+H+P x3 (n = 73) FEC x3 T+H+P x3 (n = 75) TCH+P x6 (n = 77) FEC, 5-fluorouracil, epirubicin, cyclophosphamide; H, trastuzumab; P, pertuzumab; T, docetaxel; TCH, docetaxel/carboplatin/trastuzumab Copyrights for this presentation are held by the author/presenter. Contact them at Andreas.Schneeweiss@med.uni-heidelberg.de for permission to reprint and/or distribute. 30

31 San Antonio Breast Cancer Symposium Cancer Therapy and Research Center at UT Health Science Center December 6 10, 2011 TRYPHAENA: Pathologic complete response by hormone receptor status ER- and PR-negative ER- and/or PR-positive ypt0/is Pathologic complete response (%) FEC+H+P x3 T+H+P x3 (n = 73) FEC x3 T+H+P x3 (n = 75) TCH+P x6 (n = 77) ER, estrogen receptor; FEC, 5-fluorouracil, epirubicin, cyclophosphamide; H, trastuzumab; P, pertuzumab; PR, progesterone receptor; T, docetaxel; TCH, docetaxel/carboplatin/trastuzumab Copyrights for this presentation are held by the author/presenter. Contact them at Andreas.Schneeweiss@med.uni-heidelberg.de for permission to reprint and/or distribute. 31

32 San Antonio Breast Cancer Symposium Cancer Therapy and Research Center at UT Health Science Center December 6 10, 2011 NeoSphere: Study design and objectives Patients with operable or locally advanced /inflammatory* HER2-positive BC TH (n=107) docetaxel ( mg/m 2 ) trastuzumab (8 6 mg/kg) THP (n=107) docetaxel ( mg/m 2 ) trastuzumab (8 6 mg/kg) pertuzumab ( mg) S U R G Phase II design Primary endpoint: Comparison of pcr rates TH vs THP TH vs HP THP vs TP Chemo-naïve & primary tumors >2cm (N=417) HP (n=107) trastuzumab (8 6 mg/kg) pertuzumab ( mg) TP (n=96) docetaxel ( mg/m 2 ) pertuzumab ( mg) E R Y Secondary endpoints: Clinical response DFS Breast conservation rate Biomarker evaluation Study dosing: q3w x 4 Gianni L, et al. Lancet Oncol 2011 DOI: /S (11) Copyrights for this presentation are held by the author/presenter. Contact them at gianni.luca@hsr.it for permission to reprint and/or distribute..

33 San Antonio Breast Cancer Symposium Cancer Therapy and Research Center at UT Health Science Center December 6 10, 2011 NeoSphere: Primary endpoint pathologic complete response (ITT population) p= p= p= pcr, % ± 95% CI H, trastuzumab; P, pertuzumab; T, docetaxel p values from Cochran-Mantel-Haenszel test and adjusted for multiplicity TH THP HP TP Gianni L, et al. Lancet Oncol 2011 DOI: /S (11) Copyrights for this presentation are held by the author/presenter. Contact them at gianni.luca@hsr.it for permission to reprint and/or distribute..

34 San Antonio Breast Cancer Symposium Cancer Therapy and Research Center at UT Health Science Center December 6 10, 2011 Biomarker analyses on overall population Assay method Biomarker Sample Size IHC HER2 mem H-score 416 So far none HER3 of mem the H-score analyses 377 IGF1R mem H-score 339 provided clinically PTEN cyt H-score useful 373 PTEN nuc H-score 373 pakt cyt H-score 299 assays for patient pakt nuc H-score and/or 299 qrt-pcr HER2/HER3-CR 384 regimen selection HER3-CR in addition 384 HER2-CR 387 EGFR-CR 377 or alternative to the FISH c-myc 275 ELISA (serum) sher2 (ng/ml) 381 conventional Amphiregulin assessment (pg/ml) of 384 TGF-alpha (pg/ml) 384 EGF (pg/ml) 384 Mutational analyses PIK3CA mutation 273 HER2 by IHC or FISH Copyrights for this presentation are held by the author/presenter. Contact them at gianni.luca@hsr.it for permission to reprint and/or distribute..

35 Pertuzumab 840 mg loading dose IV followed by 420 mg IV every 3 weeks simultaneously to all chemotherapy cycles.

36 San Antonio Breast Cancer Symposium Cancer Therapy and Research Center at UT Health Science Center December 6-10, 2011 TEACH Trial Eligibility HER2+ Local IHC3+ or FISH +ve Resected Stage I-IIIc primary BRCA No prior trastuzumab Neo-/adjuvant chemotherapy (CMF, anthracycline, or taxane) Appropriate endocrine therapy Stratification Time from diagnosis 4 vs >4 yrs Lymph node +ve vs -ve ER+ and/or PgR+ vs ER /PgR R A N D O M I Z E Lapatinib 1500 mg qd 1 yr N=3,147; 33 countries Aug 2006-May 2008 Placebo qd 1 yr Diagnosis 4 yr

37 San Antonio Breast Cancer Symposium Cancer Therapy and Research Center at UT Health Science Center December 6-10, 2011 TEACH Primary Endpoint: K-M Plot of DFS in ITT Population Time From Randomization HR 0.83 ( ); p=0.053 a Lapatinib Placebo Median Follow up: 4 years 0.0 Number of patients at risk Lapatinib 1500 mg Placebo a p value based on 2-sided stratified log-rank test 37 This presentation is the intellectual property of the authors/presenter. Contact them at pgoss@partners.org for permission to reprint and/or distribute.

38 San Antonio Breast Cancer Symposium Cancer Therapy and Research Center at UT Health Science Center December 6-10, 2011 TEACH: Forest Plot of DFS for Subgroups in ITT Population L=lapatinib; P=placebo. 38 This presentation is the intellectual property of the authors/presenter. Contact them at for permission to reprint and/or distribute.

39 BOLERO-2 (Ph III): Everolimus in Advanced BC N = 724 Postmenopausal ER+ Unresectable locally advanced or metastatic BC Recurrence or progression after letrozole or anastrozole R 2:1 EVE 10 mg daily + EXE 25 mg daily (n = 485) Placebo + EXE 25 mg daily (n = 239) Stratification: Sensitivity to prior hormone therapy and presence of visceral metastases Endpoints Primary: PFS (local assessment) Secondary: OS, ORR, QOL, safety, bone markers, PK BC = breast cancer; ER+ = estrogen receptor-positive; EVE = everolimus; EXE = exemestane; ORR, overall response rate; OS = overall survival; PFS = progression-free survival; PK = pharmacokinetics; QOL = quality of life. Hortobagyi G et al. SABCS 2011 (Abstract #S3-7) 39

40 BOLERO-2 (12 mo f/up): PFS Local 100 Probability (%) of Event Number of patients still at risk EVE PBO + EXE EXE (E/N (E/N = 267/485) 190/239) Time (weeks) HR = 0.44 (95% CI: ) Log rank P value: <1 x EVE + EXE: 7.4 months PBO + EXE: 3.2 months Everolimus Placebo Hortobagyi G. et al, SABCS 2011 (Abstract #S3-7) 40

41 BOLERO-2 (12 mo f/up): PFS in Subgroups Favors Everolimus + Exemestane Subgroups (N) Favors Placebo + E All (724) Age <65 (449) 65 (275) Hormonal sensitivity YES (610) NO (114) Visceral metastasis YES (406) NO (318) Baseline ECOG PS 0 (435) 1, 2 (274) Prior chemotherapy YES (493) NO (231) No. of prior therapies 1 (118) 2 (217) 3 (389) Non-NSAI hormonal therapy YES (398) NO (326) PgR status positive YES (523) NO (184) Hazard Ratio PFS = progression-free survival; PgR = progesterone receptor; NSAI = nonsteroidal aromatase inhibitor; ECOG PS = Eastern Cooperative OncologyGroup performance status. Hortobagyi G et al. SABCS 2011 (Abstract #S3-7) 41

42 BOLERO-2 (12 mo f/up): Response & Clinical Benefit Percent Everolimus + Exemestane Placebo + Exemestane 12.0% P < % Response 50.5% P < % Clinical Benefit Hortobagyi G. et al, SABCS 2011 (Abstract #S3-7) 42

43 TAMRAD (Ph II): Tamoxifen ± Everolimus in Advanced BC 111 postmenopausal women with ER+ advanced BC previously treated with an AI were randomized in a phase II trial 1.0 Probability of Progression HR = 0.54 Log-rank P = TAM: 4.5 mos TAM + EVE: 8.6 mos Months AI = aromatase inhibitor; BC = breast cancer; ER+ = estrogen receptor-positive; EVE = everolimus; TAM = tamoxifen. Bourgier C et al. ECCO/ESMO 2011 (Abstract #5005) 43

44 This presentation is the intellectual property of the author/presenter. Contact them at for permission to reprint and/or distribute. San Antonio Breast Cancer Symposium - Cancer Therapy and Research Center at UT Health Science Center December 6-10, 2011 HER2- Non-Responder Study Design Pw HER-2 negative 2nd core NC R Core biopsy R EC +/- B +/- Bevacizumab T +/- B RAD001 Pw RAD Surgery PR CR/ +/- Bevacizumab E = Epirubicin C = Cyclophosphamide T = Docetaxel B = Bevacizumab Pw = Paclitaxel, weekly (80 mg/m 2 : day 1 q day 8-12 weeks) R = RAD001 (5 mg / day from day 13 after a dose escalation starting from 2.5 mg every other day to 5mg every day)

45 San Antonio Breast Cancer Symposium - Cancer Therapy and Research Center at UT Health Science Center December 6-10, 2011 HER2- Non-Responder pcr (no invasive & no non-invasive residuals in breast & nodes based on central pathology report review N=395) P= % N= % This presentation is the intellectual property of the author/presenter. Contact them at publication@germanbreastgroup.de for permission to reprint and/or distribute.

47 CAMPUS INNENSTADT UND GROSSHADERN KLNIK UND POLIKLINIK FÜR FRAUENHEILKUNDE UND GEBURTSHILFE SABCS 2011: persönliches Fazit Starke deutsche Präsenz (Vorträge, Posterdiskussionen, Poster) studiengruppenübergreifend (AGO-B, GBG, WSG) Innovative neue Konzepte (DETECT III, Aphinity, ADAPT) Klinische Daten verfestigen sich: keine routinemässige Axilladissektion bei positivem Sentinel (cn0) adjuvante Bisphosphonate in Subgruppen Neue klinisch relevante (practice changing) Daten: BOLERO 2: Everolimus (RAD 001) CLEOPATRA: Pertuzumab Tumorbiologie-basierte Indikationsstellung wird immer wichtiger Umsetzung in klinische Praxis in Deutschland: AGO-State-of-the- Art 2012 (Frankfurt, ) München, 21/01/12 Prof. Harbeck Wintersymposium 47

49 CAMPUS INNENSTADT UND GROSSHADERN KLNIK UND POLIKLINIK FÜR FRAUENHEILKUNDE UND GEBURTSHILFE Evidenzbasierte Brustkrebstherapie AGO (DKG, DGGG) München, 21/01/12 Prof. Harbeck Wintersymposium 49