T. Cufer - Breast cancer - State of the art for advanced breast cancer

Metastatic BreastCancer Treatment:State of the Art Tanja Cufer, MD, PhD University Clinic Golnik Medical Faculty, Ljubljana EORTC BCG, ChairESO Masterclass; Amman 2011

Metastatic Breast Cancer (MBC) The survival of pts with 5-year survival of MBC pts in metastatic disease is Slovenia improving MBC is still: 20 18  Incurable but highly 16 treatable 14 1980-85 1986-90  Chronic disease 12 Survival (%) 1990-95 10 The goal of treatment: 8 1996-00 2000-05  Control of symptoms 6 4  Prolongation of life 2  Good quality of life 0

Multidisciplinary Treatment Modalitiesin MBC Systemic therapy  Endocrine therapy  Chemotherapy  Targeted systemic therapy Radiotherapy (bone, CNS mets) Surgery (solitary lesions) Supportive therapy (bisphosphonates) Palliative medicine

1st main question:Optimal systemic therapy in first- line treatment?

Tailoring Systemic Therapy in MBC  Disease-related factors  Biology of disease  ER/PR status  HER2 status  Proliferation  Disease-free interval  Tumor burden (number & site of mets)  Need for rapid disease control  Previous systemic therapy  Patient-related factors  PS  Age  Co-morbidities  Patient’s preferences

Individualized Treatment SelectionHER2 Endocrine responsive Endocrine non-responsive (HR+, long DFI, soft (HR-/uncertain, short DFI, ER tissue/bone mets) visceral mets)HER2- ET CTnegativeHER2- positive HER2 directed + ET HER2-directed + CT Thargeted therapies comes first!

2nd main question:Repeating ER/PR and HER2 status at the time of progression?

ASCO 2010: Significant Rate of Discordance Between Primary and Metastases #1007 #CRA 1008 #1009 Studies Amir et al. Locatelli et al. Karlsson et al. N=271 N=255 N=477 prospective retrospective retrospective (liver) Would you deny a(12%) 22/197 (11%) 123/336 (36%)ER+ primary with loss in recurrence 21/174 patient a targetedER- primary with gain in recurrence 8/57 (14%) 15/58 (25%) 32/141 (22%) treatment due to changes in the 32%Overall ER discordance rate 12% 14.5%Overall PR discordance ratemetastatic site? 48% 34% 43%HER2- primary with gain in recurrence 9/197 (4.6%) 7/118 (5.9%) n.d.HER2+ primary with loss in recurrence 3/24 (12.5%) 17/54 (31.5%) n.d.Change in management from results of 15% 12% n.d.recurrence biopsyDiscussion ASCO 2010: Richardson AL

Endocrine Therapy for MBC Premenopausal patients  Tamoxifen  OAS  OAS +Tamoxifen  OAS + AI Postmenopausal patients  Als  Tamoxifen  Fulvestrant

Combined Tamoxifen and LHRH Agonist vs LHRH Agonist Alone in Premenopausal Advanced Breast Cancer: A Meta-Analysis of Four Randomized Trials End Point LHRH agonist LHRH agonist HR 95%CI p alone + Tamoxifen N=256 N=250Median survival, years 2.5 2.9 0.78 0.63-0.96 0.02Median PFS, months 5.4 8.7 0.70 0.58-0.85 0.0003Objective response % 29.7 38.8 0.67 0.46-0.96 0.03 LHRH+TAM LHRHKlijn, et al. J Clin Oncol 2000;19.

Randomized Phase III Trials of AIs vs. Tamoxifen as First-line Treatment of Postmenopausal MBC Anastrozole1 Anastrozole2 Letrozole3 Exemestane4No. patients 170 vs 182 340 vs 328 453 vs 454 182 vs 189ORR, % 21 vs 17 33 vs 33 32 vs 21* 46 vs 31*CBR, % 59 vs 46* 56 vs 56 50 vs 38* 66 vs 49*TTP or PFS, months 11 vs 6* 8 vs 8 9 vs 6* 10 vs 6*ER status unknown, % 11 vs 11 56 vs 54 34 vs 33 15 vs 11ORR = overall response rate; CBR = clinical benefit rate; TTP = time to progression; PFS = progression free survival; ER = estrogen receptor *Statistically significant difference 1. Nabholtz JM, et al. J Clin Oncol. 2000;18 2. Bonneterre J, et al. J Clin Oncol. 2000;18 3. Mouridsen H, et al. J Clin Oncol. 2003;21 4. Paridaens R, et al. J Clin Oncol. 2008;26

Hormonal Therapy in PostmenopausalMBC: Aromatase Inhibitors All three AIs showed higher RR and longer TTP compared to Tam in first line setting; no differences in long term OS (Mouridsen et al JCO 2003; Bonneterre et al Cancer 2001, Paridaens et al, ASCO 2004); All three AIs seem to be equally effective with slight differences in untoward effects (Rose et al ASCO 2002, Cameron et al , ASCO 2004, Mayordomo et al, ASCO 2006) The efficacy of AIs after Tam is comparable to the efficacy of Tam after AIs (Thurlimann et al, EJCancer 2003) Steroid inactivator exemestane is effective after failure to nonsteroidal AIs, nonsteroidal AIs are effective after failure to exemestane (Thurlimann et al, EJCancer 1997, Bertelli G, et al. Oncology. 2005)

FIRST: Fulvestrant 500 mg vs. Anastrozole as First-Line 1.0 Proportion of patients alive and progression-free 0.8 Fulvestrant 500 mg Anastrozole 1 mg 0.6 0.4 0.2 HR = 0.66 (95% CI: 0.47-0.92) P = .01 0.0 0 6 12 18 24 30 36 42 48 Time (months) Number of patients at risk: Fulvestrant 500 mg 102 74 65 52 45 34 20 6 0 Anastrozole 1 mg 103 69 55 39 30 21 8 2 0 CI = confidence interval; HR = hazard ratio; TTP = time to progressionRobertson JF, et al. Cancer Res. 2010;70: Abstract S1-3.

How to Overcome Resistance to ET ?  mTORC1 activates ER in a ligand-independent fashion1  Estradiol suppresses apoptosis induced by PI3K/mTOR blockade2  Hyperactivation of the PI3K/mTOR pathway is observed in endocrine- resistant breast cancer cells3  mTOR is a rational target to enhance the efficacy of hormonal therapy1. Bjornsti MA, et al. Nat Rev Cancer. 2004;4(5):335-348. 2. Crespo JL, et al. Microbiol Mol Biol Rev. 2002;66(4):579-591.3. Huang S, et al. Cancer Biol Ther. 2003;2(3):222-232. 4. Mita MM, et al. Clin Breast Cancer. 2003;4(2):126-137.5. Wullschleger S, et al. Cell. 2006;124(3):471-484. 6. Johnston SR. Clin Cancer Res. 2005;11(2 Pt 2):889S-899S.

TAMRAD: Tamoxifen +/- Everolimus as Second- Line After AIs Failure 1.0 0.9 Probability of survival 0.8 0.7 0.6 0.5 0.4 TAM TAM + RAD 0.3 0.2 Hazard Ratio (HR) = 0.32 (95% CI: 0.15-0.68) Exploratory log-rank: P = .0019 0.1 0.0 0 3 6 9 12 15 18 21 24 27 30 33 36 Months Patients at risk:TAM + RAD: n = 54 53 51 49 49 45 38 26 14 6 0 TAM: n = 57 55 53 50 44 38 30 22 9 4 0CI = confidence interval; HR = hazard ratio; RAD = RAD001; TAM = tamoxifenBachelot T, et al. Cancer Res. 2010;70: Abstract S1-6.

BOLERO-2: Exemestane +/- Everolimusin AI Refractory Disese N = 724 Everolimus 10 mg/day + PFS Exemestane 25 mg/dayPostmenopausal (N = 485) 2 OSER+ HER2- ABC ORR refractory to 1 Bone Markers letrozole or Placebo + Safety anastrozole Exemestane 25 mg/day PK (N = 239)  Stratification:  Sensitivity to prior hormonal therapy  Presence of visceral disease  No crossoverABC: advanced breast cancer, NSAI: non steroidal aromatase inhibitors, HER2-: human epidermal growth factor receptor 2 – negative;PFS: progression-free survival; PK: pharmacokineticsBaselga J, et al. Eur J Cancer Suppl. 2011;47(Suppl 2): Abstract: 9LBA.

BOLERO-2 Primary Endpoint: PFS Local Assessment HR = 0.43 (95% CI: 0.35–0.54) 100 Log rank P value = 1.4 x 10 -15 80 EVE + EXE: 6.9 months Probability of Event, % PBO + EXE: 2.8 months 60 40 20 Everolimus + Exemestane (E/N = 202/485) Placebo + Exemestane (E/N = 157/239) 0 0 6 12 18 24 30 36 42 48 54 60 66 72 78 Time, weeks No. of Patients Still at Risk: Everolimus 485 398 294 212 144 108 75 51 34 18 8 3 3 0 Placebo 239 177 109 70 36 26 16 14 9 4 3 1 0 0Baselga J, et al. Eur J Cancer Suppl. 2011;47(Suppl 2): Abstract: 9LBA.

Chemotherapy for MBCCombination Chemotherapy or Sequential Use ofMonotherapy? Most trials and meta-analysis compare single agent vs. combination and NOT sequential use of single agents vs. combination CT. The majority of trials show that combination CT yields higher RR, in some higher PFS, higher toxicity and no or quite small survival benefit.

Chemotherpy Agents = Survival Gains Pooled analysis of 6 consecutive trials of first-line CT in MBC: - Clear evidence of an increase in OS during the past 20 years, starting with the inclusion of paclitaxel 100 90 80 1998-2001 70 Median OSProbability % 1995-1997 60 1992-1994 - 18.0 mos, in 1983-1986 50 1987-1989 - 17.2 mos, in 1987-1989 1983-1986 40 - 19.2 mos, in 1992-1994 30 - 26.1 mos, in 1995-1997 - 23.6 mos, in 1998-2001 cohorts 20 (P for heterogeneity .0001) 10 0 0 1 2 3 4 5 6 7 8 Years CT, chemotherapy; OS, overall survival Gennari A, et al. Cancer. 2005;104(8):1742-1750.

Randomized Studies with Crossover Following in the Monotherapy Arm Time to Overall Author Comparison Number of Response Rate Progression Survival Year (x number of cycles) patients (%) (months) (months) Alba A x 3 Doc x 3 144 61 10.5 22.3 2004 A + Doc x 6 51 9.2 21.8 Beslija Doc  X 100 40 7.7 19.0 2006 Doc + X 68* 9.3* 22.0* Conte E x 4  Pac x 4 202 58 10.8‡ 26.0 2004 E + Pac x 8 58 11.0‡ 20.0 Koroleva Doc x 4  A x 4 193 56 6.9 13.8 2001 A + Doc x 8 49 6.7 11.9 A + Doc║ x 8 59 8.3 14.5 Sjöstrom Doc 238 42* 6.3* 10.4 1999 MF 21 3.0 11.1 Sledge A 739 36 5.8¶ 18.9 2003 Pac 34 6.0¶ 22.2 A + Pac 47* 8.0*¶ 22.0 Soto X  Pac or Doc 368 45 8.4‡ 31.5 2006 X + Pac 64* 6.7‡ 33.1 X + Doc 75* 8.1‡ 28.5 Tomova Doc x 4 G x 4 100 28 6.7 15.9 2008 Doc + G x 8 31 7.0 15.5 *Denotes statistically significant result with P≤.05Cardoso F, et al. J Natl Cancer Inst. 2009;101(17):1174-1181

COMBINATION SEQUENTIAL SINGLE AGENTS >RR Similar survival ! <ToxicityFaster symptom/disease control Better overall QoL Better management of resources

New Cytotoxic Agents New cytotoxic agents  Targeting microtubules: Eribulin, Epothilones “Old” agents in new formulations  Capecitabine (considered standard in A&T pretreated pts)  Liposomal anthracyclines  New formulations of anti-microtubules: albumin bound, nab- paclitaxel “Old” agents in new indications  Platinum & Alkylating agents for TN

EMBRACE: A Phase III Study of Eribulin inHeavily Pre-treated pts: Overall Survival (ITT) 1.0 1-Year Survival Eribulin (n = 508) 53.9% 0.8 TPC (n = 254) 43.7% Survival Probability Eribulin median 13.12 months 0.6 TPC HR* 0.81 (95% CI: 0.66, 0.99) 0.4 median 10.65 months P value† = 0.041 0.2 2.47 months 0.0 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 Overall Survival, monthsTwelves C, et al. J Clin Oncol. 2010;28(15s): Abstract CRA1004.

What is the optimal duration of chemotherapy ?

U1 Results: Progression Free Survival Optimal Duration of Study Longer better Shorter better %Weight HR 95%CI Coates 1987 13 0.56 0.44-0.71 Chemotherapy? Harris 1990 Muss 1991 2 3 1.18 0.26 0.65-2.15 0.16-0.43 Ejlertsen 1993 28 0.71 0.61-0.83 Gregory 1997 10 0.70 0.53-0.92 Falkson 1998 5 0.46 0.31-0.68 Bastit 2000 11 0.65 0.50-0.84 Nooij 2003 8 0.67 0.50-0.90 Gennari 2006 6 1.01 0.71-1.43 Majordomo 2009 8 0.77 0.57-1.05 Alba 2010 6 0.53 0.37-0.76 Overall 100 0.64 0.66 0.55-0.76 0.60-0.72U1 0.10 1.00 10.00 Results: Overall Survival Test for heterogeneity, p=0.001 Test for treatment effect, p<0.001 Study Longer better Shorter better %Weight HR 95%CI Coates 1987 13 0.79 0.62-1.01 Harris 1990 Muss 1991 2 5 1.06 1.11 0.57-1.97 0.74-1.67  Longer CT duration: Ejlertsen 1993 Gregory 1997 17 5 0.78 0.81 0.63-0.97 0.54-1.21  36% reduction in the risk of Falkson 1998 8 0.94 0.69-1.28 progression (HR 0.64; 95% Bastit 2000 Nooij 2003 18 17 0.96 1.03 0.78-1.18 0.83-1.27 CI 0.55 – 0.76) Gennari 2006 Majordomo 2009 4 7 1.12 0.94 0.73-1.72 0.67-1.32  9% reduction in the risk of Alba 2010 5 0.86 0.58-1.27 death (HR 0.91; 95% CI 0.84- Overall 0.10 1.00 10.00 100 0.91 0.84-0.99 0.99) Test for heterogeneity, p=0.69 Test for treatment effect, p=0.044 25 Gennari et al, ESMO 2010

Targeted Therapies in MBC HER2-directed therapy (considered standard in HER2+ disease) PARP inhibitors Antiangiogenic agents

Anti-HER2 Therapy in Combination with Chemotherapy in HER2-Positive MBC TTP OS Trial Treatment ORR (%) (months) (months)Slamon et al.1; Trastuzumab + 7.1 vs. 25.1 vs. 49 vs. 17*Smith et al. 2 paclitaxel vs. paclitaxel 3.0* 18.0* Trastuzumab + 11.7 vs. 31.2 vs.Marty et al.3 61 vs. 34* 6.1* 22.7* docetaxel vs. docetaxelDi Leo et al. 4 Lapatinib + paclitaxel 8.5 vs. 24.0 vs.(ErbB2+ 63 vs. 38* vs. paclitaxel 5.8* 19.8*patients only) Lapatinib + paclitaxel 9.7 vs. 27.8Guan et al. 5 69 vs. 50* 6.5* vs.20.5* vs. Paclitaxel *= statistically significant1. Slamon et al. N Engl J Med 2001;344, 2. Smith et al. Anticancer Drugs 2001;12 Suppl 4:S3–10, 3. Marty et al. J Clin Oncol 2005;23, 4. Di Leo et al. Clin Oncol 2008;26, 5. Guan et al. 33rd SABCS 2010; Abstract P3-14-24

First-line Treatment with Trastuzumab + Docetaxel or Vinorelbine in ErbB2+ MBC: HERNATA StudyAnderssen M, et al. J Clin Oncol 2011;29

Anti-HER2 Therapy in Combination withEndocrine Therapy in ER+/HER2+ MBC  Anastrozole + Trastuzumab (TANDEM)1  CB 28 v 43%; PFS 2.4 v 4.8 months   Letrozole + Lapatinib (EGF30008)2  CB 29 v 48%; PFS 3.0 v 8.2 months1. Kaufman, et al. J Clin Oncol 27 2009, 2. Johnston, et al. J Clin Oncol 27 2009,

TANDEM: Evaluation of Anastrozole +/- Trastuzumab in HER2+/HR+ MBC 100 A A+H Outcome P Value (n = 104) (n = 103) Progression-Free 80 Events, n 99 87 Survival (%) 60 Median PFS, mos 2.4 (2.0-4.6) 4.8 (3.7-7.0) .0016 (95% CI) 40 20 0 0 5 10 15 20 25 30 35 40 45 50 55 60 2.4 months Months A+H n = 103 48 31 17 14 13 11 9 4 1 1 0 0 A n = 104 36 22 9 5 4 2 1 0 0 0 0 0Kaufman, et al. J Clin Oncol 2009.

TANDEM: Evaluation of Anastrozole +/- Trastuzumab in HER2+/HR+ MBC Anastrozole N=207 Anastrozole +Median age 55 years TrastuzumabVisceral disease 1/3 Prior chemo 1/2 Cross-over 70% 6,8% Response rate 20,3% p 0.0016 2,4m Median PFS. 4,8m 23,9m Median O.S. 28,5m 32,1m Median O.S. 41,9m if no liver mets p 0.03Trastuzumb added to anastrozole  RR, PFS (and possibly OS if no liver mets) IMPORTANCE OF STARTING BIOLOGICAL AGENT SOONMackey, et al. SABC 06;abst.03. Adapted from M. Piccart

Current Evidence Based Options of Anti-HER2 Treatment Beyond TrastuzumabProgression (Phase III trials) Continuing trastuzumab (GBG 26 / BIG 3-05 study) Lapatinib + capecitabine (EGF100151 study) Lapatinib + trastuzumab (EGF104966 study)

Comparison of Three Prospective Phase IIITrials on Anti-HER2 Treatment BeyondTrastuzumab Progression GBG-26a EGF100151b EGF104900a (n=156) (n=399) (n=296)Regimen XH X XL X LH LORR, % 48 27 32 17 10 7TTPc HR 0.69 (p=0.03) 0.72 (p=0.01) 0.73 (p=0.01) Median, 8.2 5.6 5.5 4.2 2.8 1.9 monthsOS HR 0.76 (p=0.26) 0.78 (p=0.18) 0.74 (p=0.02) Median, 25.5 20.4 15.6 15.3 14.0 9.5 months aVon Minckwitz et al 2008; O’Shaughnessy et al 2008; bInvestigator Assessment, US Lapatinib Prescribing Information & Cameron et al 2008;

New HER2-directed Agents Pertuzumab (first-in-class ErbB dimerisation inhibitor)  Phase 2 trials completed, undergoing phase 3 in combination with trastuzumab (CLEOPATRA trial) Neratinib (oral, pan-ErbB TKI)  Phase 2 trials in monotherapy and in combination with paclitaxel or vinorelbine completed, undergoing phase III combination trial with paclitaxel (NEFERTT trial) Afatinib (oral irreversible ErbB1 and 2 inhibitor)  Phase III trial in combination with vinorelbine (Lux-Breast1) Trastuzumab - DM1 (HER2-targeted antibody-drug conjugate)  In phase2 trial comperable efficacy with better toxicity profile compared to trastuzumab and docetaxel  Ongoing phase 3 trials

TDM4450g : Progression-Free Survival Median Hazard Log-rank PFS, mos ratio 95% CI P value Trastuzumab 1.0 + docetaxel (n=70) 9.2 0.364– 0.594 .0353 Proportion Progression-Free T-DM1 (n=67) 14.2 0.968 0.8 0.6 0.4 0.2 0.0 0 2 4 6 8 10 12 14 16 18 20 Time, monthsNumber of patients at riskT+D 70 66 63 53 43 27 12 4 2 2 0T-DM1 67 60 51 46 42 35 22 15 6 3 0Hazard ratio and log-rank P value were from stratified analysis.Hurvitz S, et al. Eur J Cancer Suppl. 2011;47(Suppl 2): Abstract 5001.

Biological agents for HER-2 negative disease

Bevacizumab: First-Line MBC Meta Analysis E2100 Paclitaxel RANDOMIZE Chemo + OptionalPreviously Treat Second-line AVADO No BVUntreated Chemo + BV Docetaxel until (AVADO and MBC Chemo + PD RIBBON-1 BV only) RIBBON-1 Capecitabine, Taxane, or Anthracycline O’Shaugnessy J, et al. J Clin Oncol. 2010;28(15S): Abstract 1005.

Bevacizumab in MBC RIBBON-1: E21001 AVADO2 Capecitabine3 RIBBON-1: A/T3Placebo (Pl) controlled No Yes Yes Yes q 3 wk WeeklyChemotherapy q 3 wk docetaxel (D) Capecitabine (C) docetaxel/nabPAC/FA paclitaxel (P) C/EC/FEC 10 mg/kg 7.5 or 15 mg/kg 15 mg/kg 15 mg/kgDose of bevacizumab (B) q 2 wk q 3 wk q 3 wk q 3 wk P P+B D+PI D+B C+PI C+B A/T+PI A/T+BORR 25% 49% 49% 55%/63% 24% 35% 38% 51%PFS, months 5.9 11.8 80 8.7/8.8 5.7 8.6 8.0 9.2 0.79 (7.5 mg) 0.60 P = .0318 0.69 0.64HR P<.0001 0.72 (15 mg) P = .0002 P<.0001 P = .0099OS, months 25.2 26.7 NR NR 21.2 29 23.8 25.2 0.88 0.92 (7.5 mg) 0.85 1.03HR P = .16 0.86 (15 mg) P = .27 P = .83 Meta-Analysis (O’Shaughnessy et al ASCO 2010) PFS: 2.5 months, OS: 0.3 months1.Miller K, et al. N Eng J Med. 2007;357(26), 2. Miles D, et al. J Clin Oncol. 2008;26:(May 20 Suppl): AbstractLBA1011, 3. Robert NJ, et al. J Clin Oncol. 2009;27(15S): Abstract 1005.

Multi-center, Randomized Open-label Phase III RegistrationNTrial of Iniparib in mTNBC = 519 Patient Population:  mTNBC Gem/Carbo (GC) Crossover allowed  0–2 prior chemo for (N= 258) metastatic TNBC to GCI following Gemcitabine 1000 mg/m2 IV d 1, 8 Disease Progression*  Stable CNS metastases Carboplatin AUC2 IV d 1, 8 (central review) allowed 21-day cycles Stratification: R  No prior chemo vs 1–2 Gem/Carbo + Iniparib (GCI) prior chemo for mTNBC (N= 261) Gemcitabine - 1000 mg/m2 IV d 1, 8 Carboplatin - AUC2 IV d 1, 8 Endpoints: Iniparib - 5.6 mg/kg IV d 1,4,8,11  Primary: OS, PFS 21-day cycles  Secondary: ORR, safety/tolerability96% (n=152) of progressing patients crossed over to GCI at time of primary analysisO’Shaughnessy et al, ASCO 2011

Efficacy Endpoints – ITT Population GC* GCI GC GCI PFS OS (N=258) (N=261) (N=258) (N=261) Median PFS, mos 4.1 5.1 Median OS, mos 11.1 11.8 (95% CI) (3.1, 4.6) (4.2, 5.8) (95% CI) (9.2, 12.1) (10.6, 12.9) HR (95% CI) 0.79 (0.65, 0.98) HR (95% CI) 0.88 (0.69, 1.12) 1.0 p-value 0.027 1.0 p-value 0.28 Probability of Progression Free Survival 0.9 0.9 0.8 0.8 Probability of Survival 0.7 Pre-specified alpha = 0.01 0.7 Pre-specified alpha = 0.04 0.6 0.6 0.5 0.5 0.4 0.4 0.3 0.3 0.2 0.2 0.1 0.1 0 0 0 2 4 6 8 10 12 14 16 0 2 4 6 8 10 12 14 16 Months Since Study Entry MonthsNo. at risk No. at riskGC 258 171 116 63 38 18 6 1 0 GC 258 239 214 181 151 99 38 11 0GCI 261 187 138 83 53 11 2 0 0 GCI 261 248 230 204 169 111 52 15 0O’Shaughnessy et al, ASCO 2011

Potential Solutions to Improve MBCOutcome New treatments New strategies with “old” treatments More pts in clinical trials Less than 5-10% of cancer patients participate in clinical trials in the western countries!! Biomarkers (predictive, pharmacogenetics, pharmacogenomics…) International RECOMMENDATIONS (that are followed!) (implementation of recommendations such as St Gallen increased survival EBC)

The “St Gallen” of MBC PLEASE JOIN US!!

T. Cufer - Breast cancer - State of the art for advanced breast cancer

by European School of Oncology

Accessibility

Categories

Upload Details

Usage Rights

1 Embed 1

Statistics

T. Cufer - Breast cancer - State of the art for advanced breast cancer Presentation Transcript