LAPATINIB-Resistance to small Molecule ErbB2 Tyrosine Kinase Inhibitor (TKI)

Size: px
Start display at page:

Download "LAPATINIB-Resistance to small Molecule ErbB2 Tyrosine Kinase Inhibitor (TKI)"

Transcription

1 LAPATINIB-Resistance to small Molecule ErbB2 Tyrosine Kinase Inhibitor (TKI) Prim Mr Sc Dr Suzana Vasović Institute for oncology and radiology of Serbia UMOS, X Conference, Belgrade

2 How do we translate complex molecular interactions into therapeutic benefit? 1 1. Reprinted from Cell, Volume 100. Hanahan D, Weinberg RA. The hallmarks of cancer. Pages Copyright (2000), with permission from Elsevier.

3 Why the need to understand the biological effects of targeted agents? Identify the target population Evaluate biologically active doses rather than MTD Use in minimal disease settings Chronic therapy Reduce toxicity in combination with other agents Enhance efficacy of second-generation therapies Rationale for combination therapies ( strategies to overcome resistance)

4 Signal transduction - Erb family of receptors

5 Lapatinib is an oral, small molecule, dual targeted agent for the treatment of ErbB2- positive breast cancer that acts intracellularly

6 Lapatinib inhibits both Erk and AKT signalling pathways

7 Additional benefit of intracellular mode of action of lapatinib Lapatinib provides direct inhibition of signalling pathways different to those affected by trastuzumab 1 Lapatinib is active in tumours that express p95 ErbB2, 2 which characterises a particularly aggressive phenotype of breast cancer 3 1. Nagata et al. Cancer Cell 2004;6:117 27; 2. Scaltriti et al. J Natl Cancer Inst 2007;99:628 38; 3. Saez et al. Clin Cancer Res 2006;12:424 31

8 How specific are TKIs? Examples: Lapatinib: binds only 4/113 kinases tested CI-1033 (pan- ErbB): binds ate least 36/113 Staurosporine: binds 104/113 8

9 Clinical experience with lapatinib in ErbB2- positive metastatic breast cancer patients pre-treated with trastuzumab

10 Phase III, randomised, controlled study of lapatinib plus capecitabine versus capecitabine alone (study EGF ) 1 Patients with ErbB2-positive locally advanced or metastatic breast cancer that progressed after prior anthracycline, taxane and trastuzumab (N=399) RANDOMISATION Lapatinib 1250 mg po qd continuously + capecitabine 2000 mg/m 2 /d po days 1 14 q 3 wk Capecitabine 2500 mg/m 2 /day p.o. days 1 14 q 3 wk po = oral; qd = once daily; q 3 wk = once every 3 weeks Treatment continued until progression 1. Cameron et al. Breast Can Res Treat 2008;[Epub ahead of print]; 2. Geyer et al. N Engl J Med 2006;355:

11 1. Cameron et al. Breast Can Res Treat 2008;[Epub ahead of print]. Figure Adapted from Cameron D, Casey M, Press M et al. A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab: updated efficacy and biomarker analyses. Breast Cancer Res Treat, 2008 Epub ahead of print, with kind permission of Springer Science and Business Media. Lapatinib plus capecitabine: significantly longer time-to-progression in difficult to treat population (study EGF ; independent assessment)* 1 *Primary endpoint was independently assessed time to progression 2 ; HR = hazard ratio; CI = confidence interval

12 1. Cameron et al. Breast Can Res Treat 2008;[Epub ahead of print]. Figure Adapted from Cameron D, Casey M, Press M et al. A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab: updated efficacy and biomarker analyses. Breast Cancer Res Treat, 2008 Epub ahead of print, with kind permission of Springer Science and Business Media. Lapatinib plus capecitabine: overall survival by independent assessment (study EGF100151) 1 Data presented are from an April 2006 analysis, which was conducted prior to patients being permitted to switch therapy.

13 Observations Clinical response (CR and PR) to lapatinib is generaly transient In BT474 cells: initial massive apoptosis in response to lapatinib followed by outgrowth of ER+ resistant cells The development of resistance tolapatinib in the clinic appears similar to that which occurs in cell culture

14 Non-classical ER Signaling: ER Crosstalk Enhances IGFR/HER2 Signaling * * Stephen Johnston, CCR, 2010 Crosstalk at the membrane to enhance IGFR/HER2 signaling via ER leading to TOR activation London 2012 FASDAT Advisory Board The Sheraton Skyline

15 Proposed mechanisms of acquired resistance: Akt, protein kinase B; HER, human epidermal growth factor receptor; HSP90, heat shock protein 90; IGF1R, insulin-like growth factor receptor 1; MAPK, mitogen-activated protein kinase; MET, mesenchymal epithelial transition factor; mtor, mammalian target of rapamycin; PI3K, phosphatidylinositol 3-kinase; PTEN, phosphatase and tensin homolog; VEGFR, vascular endothelial growth factor receptor.

16 LAPATINIB in ErbB2- + /ER- + mbc 1 3 Aromatase inhibitor ErbB heterodimer signal transduction Ligands Androgens Estrogen EGFR (or other ErbB) ErbB2 Non-genomic ER response lapatinib lapatinib lapatinib Estrogen receptor Citoplasm Cross talk PI3K/Akt MAPK pathway Jedro Genomic ER response Gene transcription

17 Hormonal Therapy in HER2+ ABC Regimen ORR, % PFS, mo Anastrozole + trastuzumab (N = 103) Anastrozole (N = 104) Lapatinib + letrozole (N = 642) Letrozole (N = 644) Abbreviations: ORR, overall response rate; PFS, progression-free survival. 1. Mackey JR, et al. SABCS 2006, Abstract Johnston S, et al. J Clin Oncol. 2009;27:

18 EGF30008 study design Front line MBC Postmenopausal ER+ and/or PgR+ (N=1286 including 217 HER2+) Letrozole 2.5 mg QD + Lapatinib 1500 mg QD Stratification: Visceral vs. non-measurable disease Prior hormone therapy Letrozole 2.5 mg QD + Placebo Hierarchical Statistical Analysis 1. Test HER2+ subgroup at α=0.05 (55% increase in median PFS) 2. If significant then test: ITT population at α=0.05 (30% increase in median PFS) 3. HER2- subgroup provided as supportive to determine degree HER2+ influences TTP endpoint

19 EGF30008 study results Clinical efficacy in overall population Clinical efficacy in ITT population Johnston et al. JCO

20 Model for ER/AXLdependent lapatinib resistance and the crosstalk among ER, AXL, and HER family receptors in ER-positive and HER2+ BC cells. Coactivation of AXL with HER2 leads to downstream PI3K/AKT and ERK signaling which are essential to cell growth and survival. ER blockers such as estrogen deprivation or fulvestrant reduce the expression of AXL Inhibiting both HER2and AXL is necessary to reduce the downstream PI3K/AKT and ERK signaling and cell growth. 26

21 MAIN strategy : restoration of trastuzumab/her2 sensitivity by targeting the PI3K/Akt/mTOR pathway The PI3K/Akt/mTOR signal transduction pathway is critical to cell growth, proliferation, metabolism, survival, and angiogenesis and has been implicated in several types of cancers HER2+ BC: - with high levels of phosphorylated Akt, - activating mutations of PI3CKA, - loss of PTEN have worse outcomes after trastuzumab-based therapy Activated PI3K/Akt/mTOR signaling appears to play a role in both acquired and de novo HER2 resistance. 1. Sharial, J Crown and B.T.Hennessy. Overcoming resistance and restoring sensitivity to HER2-targeted therapies in breast cancer. Annals of Oncology 2012; 23 (12):

22 Future strategies for overcoming HER2 resistance: inhibitors of the PI3K/Akt/mTOR pathway mtor interacts with ER signaling as well as growth factors including IGF-1, VEGF, and ErbB1,2 RTKs: EGFR, HER2, IGF1-R ER ER PTEN Src CoA Inactivated suppressors PI3K E Aberrations of this pathway are common in multiple cancers, including BC3,4 P Ras TSC2 TSC1 Nonnuclear/ nongenomic AKT S6K1 Activation of transcription factors Proliferation Survival Invasion mtor Cellular metabolism Angiogenesis ER Nuclear/ genomic mtor inhibitor MAPK P P P P ER P ER P CoA EREs P CoA mtor is a central regulator of multiple signaling pathways involved in cancer P CoA AP-1 TFs AP-1/SP-1 TFs-REs Gene expression (GFs, RTKs) Furthermore, hyperactivation of the PI3K/AKT/mTOR pathway has been observed in endocrine-resistant BC cells4 Inhibition of the mtor pathway may enhance endocrine sensitivity by inhibiting ligand-independent activation of the estrogen receptor Dual blockade of the mtor and endocrine pathways via mtor inhibition in combination with endocrine therapy offers clinical benefits for patients progressing on NSAIs 1. Osborne CK, et al. Annu Rev Med. 2011;62: ; 2. Yamnik RL, et al. J Biol Chem. 2009;284(10): ; 3. Samuels Y, et al. Science. 2004;304(5670):554; 4. Miller TW, et al. J Clin Invest. 2010;120(7):

23 Clinical data of everolimus in patients with trast-refractorher2+ BC

24 Current strategies for overcoming resistance: maintaining HER2-targeted therapy switching chemotherapeutic agent switching HER2-targeted therapy combining HER2 inhibitors combining HER2 inhibitors with antiestrogens (AI) combining HER2 inhibitors with m-tor inhibitors 1. Sharial, J Crown and B.T.Hennessy. Overcoming resistance and restoring sensitivity to HER2-targeted therapies in breast cancer. Annals of Oncology 2012; 23 (12):

25 EGF104900: Study design HER2 (FISH+/IHC3+) metastatic BC Progression on antracyclins taxanes trastuzumab Progression on trastuzumab in MBC R A N D O M I S A T I O N Lapatinib (oral) 1500 mg daily (n=148) Crossover allowed on lapatinib + trastuzumab arm if progression occured at least 4 weeks on the therapy Lapatinib (oral) 1000 mg daily+ trastuzumab (IV) 4 mg/kg loading dose, after 2 mg/kg weekly (n=148) Primary endpoint: PFS Secondary endpoint: OS ORR CBR Evaluation of response after 4, 8, 12, 16 weeks, afterwards every 8 weeks Evaluation by independent reviewer (po RECIST krit.) FISH = fluorescence in situ hybridisation; IHC = immunohistochemistry; MBC = metastatic breast cancer; RECIST = Response Evaluation Criteria in Solid Tumours. Blackwell et al. J Clin Oncol. 2010;28:

26 Cumulative % alive without progression EFG104900: PFS in ITT patient population Lapatinib (n=145) Lapatinib + trastuzumab (n=146) Progressed or died Median PFS 128 (88%) 8.1 weeks 127 (87%) 12 weeks P-value % Hazard ratio: 0.73 (95% CI: 0.57, 0.93) 6-months PFS L L+T 0 Patients at risk Investigator-assessed. CI = confidence interval; ITT = intent-to-treat; L = lapatinib; PFS = progression-free survival; T = trastuzumab. Blackwell et al. J Clin Oncol. 2010;28: % Time from randomization (weeks)

27 Survival rate (%) EGF104900: OS in the ITT population Died, n (%) Median p-value Lapatinib (n=145) 113 (78%) 9.5 months Lapatinib + trastuzumab (n=146) 105 (72%) 14 months % 6-months OS 80% 56% 41% 12- months OS HR: 0.75 (95% CI 0.57, 0.97) 49% patients crossed-over from the control arm (lapatinib) to receive vertical dual HER2 blockade Patients at risk Time from randomization (months) L L+T ITT = intent-to-treat; L = lapatinib; OS = overall survival; T = trastuzumab. Blackwell et al. J Clin Oncol. 2012;30:

28 Cumulative Proportion Alive EGF104900: OS subgroup analysis by hormone receptor status HR-positive 1.0 HR-negative Lap+Tras Lap Number at Risk Lap+Tras Lap Time from Randomization (Months) Lap+Tras Lap Lap+Tras N=71 Lap N=70 OS HR (95% CI) Lap+Tras N=75 Lap N=75 OS HR (95% CI) Median OS, months ( ) Median OS, months ( ) CI = confidence interval; HR = hormone receptor; Lap = lapatinib; OS = overall survival; Tras = trastuzumab. Tyverb Assessment report EMEA/H/C/000795/II/ Available at: _Assessment_Report_-_Variation/human/000795/WC pdf. Accessed September 2013.

Mechanisms of hormone drug resistance

Mechanisms of hormone drug resistance Mechanisms of hormone drug resistance Ljiljana Stamatović Institute for Oncology and Radiology of Serbia Tenth UMOS Conference, Belgrade, 16-17 th May 2015. Hormone receptor-positive breast cancer (HR+

More information

Update on the Management of HER2+ Breast Cancer. Christian Jackisch, MD, PhD Sana Klinikum Offenbach Offenbach, Germany

Update on the Management of HER2+ Breast Cancer. Christian Jackisch, MD, PhD Sana Klinikum Offenbach Offenbach, Germany Update on the Management of HER2+ Breast Cancer Christian Jackisch, MD, PhD Sana Klinikum Offenbach Offenbach, Germany Outline Treatment strategies for HER2-positive metastatic breast cancer since First

More information

Page. Objectives: Hormone Therapy Resistance: Challenges and Opportunities. Research Support From Merck

Page. Objectives: Hormone Therapy Resistance: Challenges and Opportunities. Research Support From Merck Hormone Therapy Resistance: Challenges and Opportunities Pamela. N. Munster, MD University of California, San Francisco Financial Disclosures Research Support From Merck Objectives: Understanding the current

More information

Advanced HER2+ Breast Cancer: New Options and How to Deploy Them. José Baselga MD, PhD

Advanced HER2+ Breast Cancer: New Options and How to Deploy Them. José Baselga MD, PhD Advanced HER2 Breast Cancer: New Options and How to Deploy Them José Baselga MD, PhD HER2 signaling results in a multitude of cellular effects, including increased cellular proliferation HER2 HER3 RAS

More information

Metastasi viscerali: altre opzioni oltre la chemioterapia. Ormonoterapia e Agentianti-Her2. - Valentina Sini -

Metastasi viscerali: altre opzioni oltre la chemioterapia. Ormonoterapia e Agentianti-Her2. - Valentina Sini - Metastasi viscerali: altre opzioni oltre la chemioterapia. Ormonoterapia e Agentianti-Her2 - Valentina Sini - Metastatic Breast Cancer ER- Her2-20% ER- Her2+ ER+ Her2+ 5% 15% ER+ Her2- ER+ Her2+ ER- Her2+

More information

10/15/2012. Overcoming Endocrine Therapy Resistance. The Problem in ER+ Tumors is Endocrine Therapy Resistance

10/15/2012. Overcoming Endocrine Therapy Resistance. The Problem in ER+ Tumors is Endocrine Therapy Resistance Overcoming Endocrine Therapy Resistance Joyce O Shaughnessy, MD Baylor Sammons Cancer Center Texas Oncology US Oncology Slide Credits: Hope Rugo, MD The Problem in ER+ Tumors is Endocrine Therapy Resistance

More information

Mechanisms of Resistance to. Lisa A. Carey, M.D. University of North Carolina at Chapel Hill Lineberger Comprehensive Cancer Center

Mechanisms of Resistance to. Lisa A. Carey, M.D. University of North Carolina at Chapel Hill Lineberger Comprehensive Cancer Center Mechanisms of Resistance to Hormonal Therapy Lisa A. Carey, M.D. University of North Carolina at Chapel Hill Lineberger Comprehensive Cancer Center Antagonizing Estrogen Dependent Growth Premenopausal

More information

Novel Strategies in Systemic Therapies: Overcoming Endocrine Therapy Resistance

Novel Strategies in Systemic Therapies: Overcoming Endocrine Therapy Resistance Novel Strategies in Systemic Therapies: Overcoming Endocrine Therapy Resistance Richard S. Finn, MD Division of Hematology/ Oncology Director, Translational Oncology Laboratory Geffen School of Medicine

More information

Overcoming resistance to endocrine or HER2-directed therapy

Overcoming resistance to endocrine or HER2-directed therapy Overcoming resistance to endocrine or HER2-directed therapy Jane Lowe Meisel, MD Assistant Professor of Hematology and Medical Oncology Winship Cancer Institute at Emory University 1 Background While most

More information

Systemic therapy: HER-2 update. Hans Wildiers Multidisciplinair Borst Centrum/Algemene medische oncologie UZ Leuven

Systemic therapy: HER-2 update. Hans Wildiers Multidisciplinair Borst Centrum/Algemene medische oncologie UZ Leuven Systemic therapy: HER-2 update Hans Wildiers Multidisciplinair Borst Centrum/Algemene medische oncologie UZ Leuven New drugs Strategic issues Specific anti-her2 drugs Lapa$nib /Nera$nib Baselga & Swain,

More information

La via del segnale PI3K/AKT/mTOR Inibitori di mtor nel carcinoma mammario

La via del segnale PI3K/AKT/mTOR Inibitori di mtor nel carcinoma mammario La via del segnale PI3K/AKT/mTOR Inibitori di mtor nel carcinoma mammario Alessandra Modena U.O.C. Oncologia Medica Direttore: Dott.ssa Stefania Gori Ospedale Sacro Cuore - Don Calabria 29 novembre 2016

More information

Evolving Paradigms in HER2+ MBC: Strategies for Individualizing Therapy with Available Agents

Evolving Paradigms in HER2+ MBC: Strategies for Individualizing Therapy with Available Agents Evolving Paradigms in HER2+ MBC: Strategies for Individualizing Therapy with Available Agents Kimberly L. Blackwell MD Professor Department of Medicine and Radiation Oncology Duke University Medical Center

More information

Multimedia Appendix 6 Educational Materials Table of Contents. Intervention Educational Materials Audio Script (version 1)

Multimedia Appendix 6 Educational Materials Table of Contents. Intervention Educational Materials Audio Script (version 1) Multimedia Appendix 6 Educational Materials Table of Contents Intervention Educational Materials... 1 Audio Script (version 1)... 1 Text (version 1)... 5 Slides (version 1)... 17 Audio Script (version

More information

Resistance to anti-her2 therapies. Service d Oncologie Médicale

Resistance to anti-her2 therapies. Service d Oncologie Médicale Resistance to anti-her2 therapies Pr David Khayat Service d Oncologie Médicale Groupe Hospitalier Pitié Salpêtrière -Paris Disclosure statment Trastuzumab in HER2+ MBC A major impact but resistance will

More information

Recent Update in Management of Breast Cancer: Medical Oncology. Jin Hee Ahn, M.D., PhD. 23-April-2015

Recent Update in Management of Breast Cancer: Medical Oncology. Jin Hee Ahn, M.D., PhD. 23-April-2015 2015 GBCC & 4 th IBCS 1/37 Recent Update in Management of Breast Cancer: Medical Oncology Jin Hee Ahn, M.D., PhD. 23-April-2015 Department of Oncology, Asan Medical Center, UUCM, Seoul, Korea 2/37 3/37

More information

PROGNOSTICO DE PACIENTES COM CA DE MAMA METASTATICO HER2+: PODEMOS FAZER MAIS? TDM-1 AND BEYOND!

PROGNOSTICO DE PACIENTES COM CA DE MAMA METASTATICO HER2+: PODEMOS FAZER MAIS? TDM-1 AND BEYOND! II Simpósio Internacional de Câncer de Mama para o Oncologista Clínico PROGNOSTICO DE PACIENTES COM CA DE MAMA METASTATICO HER2+: PODEMOS FAZER MAIS? TDM-1 AND BEYOND! INGRID A. MAYER, MD, MSCI Assistant

More information

Ruth M. O Regan, MD Professor and Vice-Chair for Educational Affairs, Department of Hematology and Medical Oncology, Emory University, Chief of

Ruth M. O Regan, MD Professor and Vice-Chair for Educational Affairs, Department of Hematology and Medical Oncology, Emory University, Chief of Endocrine Therapy of Advanced Breast Cancer School of Breast Oncology November 9 th 2013 Ruth M. O Regan, MD Professor and Vice-Chair for Educational Affairs, Department of Hematology and Medical Oncology,

More information

Expanding Therapeutic Strategies for HER2-Positive Metastatic Breast Cancer

Expanding Therapeutic Strategies for HER2-Positive Metastatic Breast Cancer Expanding Therapeutic Strategies for HER2-Positive Metastatic Breast Cancer Sara A. Hurvitz, MD, FACP Associate Professor of Medicine University of California Los Angeles Los Angeles, California Trastuzumab

More information

Breast cancer update. Iryna Kuchuk, MD Oncology department Meir Medical Center

Breast cancer update. Iryna Kuchuk, MD Oncology department Meir Medical Center Breast cancer update Iryna Kuchuk, MD Oncology department Meir Medical Center Overview Cancer Death Rates* Among Women, US,1930-2009 Factors Associated with Reduction In Breast Cancer Mortality Early

More information

mtor e le altre vie di trasduzione del segnale: Implicazioni cliniche Giampaolo Tortora

mtor e le altre vie di trasduzione del segnale: Implicazioni cliniche Giampaolo Tortora mtor e le altre vie di trasduzione del segnale: Implicazioni cliniche Giampaolo Tortora Cattedra di Oncologia Medica UOC Oncologia Medica du Facoltà di Medicina e Chirurgia e Azienda Ospedaliera Universitaria

More information

Best of San Antonio 2008

Best of San Antonio 2008 Best of San Antonio 2008 Ellie Guardino, MD/PhD Assistant Professor Stanford University BIG 1 98: a randomized double blind phase III study evaluating letrozole and tamoxifen given in sequence as adjuvant

More information

HER2-positive Breast Cancer

HER2-positive Breast Cancer HER2-positive Breast Cancer Multiple choices what to use when? Thomas Ruhstaller Brustzentrum St. Gallen Adjuvant setting NCIC MA5 N Engl J Med 06, 2103 6 x CEF can 6 x CMF oral HER2 + pg schlecht in allen

More information

Breast Cancer: the interplay of biology, drugs, radiation. Prof. L. Livi Università degli Studi di Firenze. Brescia, October 3rd 4th, 2013

Breast Cancer: the interplay of biology, drugs, radiation. Prof. L. Livi Università degli Studi di Firenze. Brescia, October 3rd 4th, 2013 Breast Cancer: the interplay of biology, drugs, radiation Prof. L. Livi Università degli Studi di Firenze Brescia, October 3rd 4th, 2013 BACKGROUND (1) The complex interactions between tumor-specific signaling

More information

Targe:ng HER2 in Metasta:c Breast Cancer in 2014

Targe:ng HER2 in Metasta:c Breast Cancer in 2014 Targe:ng HER2 in Metasta:c Breast Cancer in 2014 Kimberly L. Blackwell MD Professor Department of Medicine and Radia:on Oncology Duke University Medical Center Director, Breast Cancer Program Duke Cancer

More information

Endocrine Therapy 2017: Is There a Better Single Agent and when Should we Use it?

Endocrine Therapy 2017: Is There a Better Single Agent and when Should we Use it? Endocrine Therapy 2017: Is There a Better Single Agent and when Should we Use it? ET1 ET2 ET3 Targeted agent 1 Targeted agent 2 Hope S. Rugo, MD Director, Breast Oncology and Clinical Trials Education

More information

Update on Systemic Treatment of Breast Cancer

Update on Systemic Treatment of Breast Cancer Update on Systemic Treatment of Breast Cancer Christoph C. Zielinski Clinical Division of Oncology Department of Medicine I and Comprehensive Cancer Center (www.ccc.ac.at) Medical University Vienna - General

More information

Management of ErbB2-positive Breast Cancer: Insights from Preclinical and Clinical Studies with Lapatinib

Management of ErbB2-positive Breast Cancer: Insights from Preclinical and Clinical Studies with Lapatinib Review Article Jpn J Clin Oncol 2010;40(11)999 1013 doi:10.1093/jjco/hyq084 Advance Access Publication 11 June 2010 Management of ErbB2-positive Breast Cancer: Insights from Preclinical and Clinical Studies

More information

Her 2 Positive Advanced Breast Cancer: From Evidence to Practice

Her 2 Positive Advanced Breast Cancer: From Evidence to Practice Her 2 Positive Advanced Breast Cancer: From Evidence to Practice Sunil Verma MD, FRCP(C) Medical Director, Tom Baker Cancer Center Professor and Head, Department of Oncology Cumming School of Medicine,

More information

Treatment of Metastatic Breast Cancer. Prof RCCoombes Imperial College London

Treatment of Metastatic Breast Cancer. Prof RCCoombes Imperial College London Treatment of Metastatic Breast Cancer Prof RCCoombes Imperial College London Metastatic Breast Cancer: General Guidelines Specialized oncology nurses (if possible specialized breast nurses) should be part

More information

PIK3CA Mutations in HER2-Positive Breast Cancer

PIK3CA Mutations in HER2-Positive Breast Cancer 2016.4.29. GBCC PIK3CA Mutations in HER2-Positive Breast Cancer Seock-Ah Im, MD, PhD. Department of Internal Medicine Seoul National University Hospital Contents Introduction TCGA data HER2 signaling pathway

More information

William J. Gradishar MD

William J. Gradishar MD Northwestern University Feinberg School of Medicine Management of HER2+ MBC SOBO 2012 William J. Gradishar MD Betsy Bramsen Professor of Breast Oncology Director, Maggie Daley Center for Women s Cancer

More information

First-Line Ribociclib + Letrozole for Postmenopausal Women With HR+, HER2-, Advanced Breast Cancer: First Results From the Phase III MONALEESA-2 Study

First-Line Ribociclib + Letrozole for Postmenopausal Women With HR+, HER2-, Advanced Breast Cancer: First Results From the Phase III MONALEESA-2 Study First-Line Ribociclib + Letrozole for Postmenopausal Women With HR+, HER2-, Advanced Breast Cancer: First Results From the Phase III MONALEESA-2 Study Abstract LBA1 Hortobagyi GN, Stemmer SM, Burris HA,

More information

PI3K/AKT/mTOR Inhibitors in Breast Cancer

PI3K/AKT/mTOR Inhibitors in Breast Cancer PI3K/AKT/mTOR Inhibitors in Breast Cancer Dr Yoon-Sim YAP Division of Medical Oncology, National Cancer Centre Singapore Global Breast Cancer Conference 2015 Outline Overview of PI3K/Akt/mTOR Pathway Rationale

More information

Outline of the presentation

Outline of the presentation Outline of the presentation Breast cancer subtypes and classification Clinical need in estrogen-positive (ER+) metastatic breast cancer (mbc) Sulforaphane and SFX-01: the preclinical evidence STEM Phase

More information

Pro: Hormone Therapy in HR positive MBC is the preferred option!

Pro: Hormone Therapy in HR positive MBC is the preferred option! Pro: Hormone Therapy in HR positive MBC is the preferred option! Alexandru Eniu, MD, PhD Medical Oncologist Head, Day Hospital Unit Department of Breast Tumors Cancer Institute Ion Chiricuţă Cluj-Napoca,

More information

A vision for HER2 future

A vision for HER2 future School of Medical Oncology Department of Medical and Biological Sciences - University of Udine Department of Oncology - University Hospital of Udine A vision for HER2 future Current therapeutic algorithm

More information

Recent advances in the management of metastatic breast cancer in older adults

Recent advances in the management of metastatic breast cancer in older adults Recent advances in the management of metastatic breast cancer in older adults Laura Biganzoli Medical Oncology Dept New Hospital of Prato Istituto Toscano Tumori Italy Important recent advances in the

More information

Agents in the Treatment of ER+ Aromatase Inbitor-Resistant Metastatic Breast Cancer: M-THOR Inhibitors

Agents in the Treatment of ER+ Aromatase Inbitor-Resistant Metastatic Breast Cancer: M-THOR Inhibitors Agents in the Treatment of ER+ Aromatase Inbitor-Resistant Metastatic Breast Cancer: M-THOR Inhibitors Valero, M.D., Professor of Medicine and Deputy Chairman Department of Breast Medical Oncology The

More information

Endocrine Therapy of Advanced Breast Cancer School of Breast Oncology November 2012

Endocrine Therapy of Advanced Breast Cancer School of Breast Oncology November 2012 Endocrine Therapy of Advanced Breast Cancer School of Breast Oncology November 2012 Ruth M. O Regan, MD Professor and Vice-Chair for Educational Affairs, Department of Hematology and Medical Oncology,

More information

Open Clinical Trials: What s Out There Now Paula D. Ryan, MD, PhD

Open Clinical Trials: What s Out There Now Paula D. Ryan, MD, PhD Open Clinical Trials: What s Out There Now Paula D. Ryan, MD, PhD Hanahan and Weinberg, 2000 Acquired Capabilities of Cancer Clinical Trials When should I consider a clinical trial? How do I find the right

More information

Cáncer de mama HER2+/RE+ vs HER2+/RE : Una misma enfermedad? Dra E. Ciruelos Departamento de Oncología Médica Hospital Universitario 12 de Octubre

Cáncer de mama HER2+/RE+ vs HER2+/RE : Una misma enfermedad? Dra E. Ciruelos Departamento de Oncología Médica Hospital Universitario 12 de Octubre Cáncer de mama HER2+/RE+ vs HER2+/RE : Una misma enfermedad? Dra E. Ciruelos Departamento de Oncología Médica Hospital Universitario 12 de Octubre Recurrence of HER2-positive breast cancer (A) Time to

More information

Advances in Breast Cancer Therapeutics in the Adjuvant and Metastatic Settings. Eve Rodler, MD University of California at Davis October 2016

Advances in Breast Cancer Therapeutics in the Adjuvant and Metastatic Settings. Eve Rodler, MD University of California at Davis October 2016 Advances in Breast Cancer Therapeutics in the Adjuvant and Metastatic Settings Eve Rodler, MD University of California at Davis October 2016 17th Annual Advances in Oncology September 30-October 1, 2016

More information

Emerging Agents in HER2-positive Disease. Mary Cianfrocca, DO Director, Breast Oncology Program Banner MD Anderson Cancer Center Gilbert, AZ

Emerging Agents in HER2-positive Disease. Mary Cianfrocca, DO Director, Breast Oncology Program Banner MD Anderson Cancer Center Gilbert, AZ Emerging Agents in HER2-positive Disease Mary Cianfrocca, DO Director, Breast Oncology Program Banner MD Anderson Cancer Center Gilbert, AZ Signal Transduction by the HER Family and Potential Mechanisms

More information

Inibitori delle chinasi ciclino dipendenti nel trattamento della malattia metastatica HR-positiva Gli studi clinici

Inibitori delle chinasi ciclino dipendenti nel trattamento della malattia metastatica HR-positiva Gli studi clinici Inibitori delle chinasi ciclino dipendenti nel trattamento della malattia metastatica HR-positiva Gli studi clinici Laura Orlando UOC Oncologia & Breast Unit Brindisi Verona 22/04/2016 Summary Studi con

More information

HER2-Targeted Rx. An Historical Perspective

HER2-Targeted Rx. An Historical Perspective HER2-Targeted Rx An Historical Perspective Trastuzumab: Front Line Rx for MBC Median 20.3 v. 25.1 mo P = 0.046 HR 0.8 65% of control patients crossed over Slamon D, et al. N Engl J Med, 2001; 344:783 Trastuzumab:Front-line

More information

Alternativas terapéuticas en fenotipo triple negativo Javier Cortes, Hospital Universitario Ramon y Cajal, Madrid

Alternativas terapéuticas en fenotipo triple negativo Javier Cortes, Hospital Universitario Ramon y Cajal, Madrid Alternativas terapéuticas en fenotipo triple negativo Javier Cortes, Hospital Universitario Ramon y Cajal, Madrid Vall d Hebron Institute of Oncology (VHIO), Barcelona Triple Negative Breast Cancer Immunohistochemistry

More information

Highlitghs in MBC First and second line endocrine treatments. Antonio Frassoldati Oncologia Clinica Ferrara

Highlitghs in MBC First and second line endocrine treatments. Antonio Frassoldati Oncologia Clinica Ferrara Highlitghs in MBC First and second line endocrine treatments Antonio Frassoldati Oncologia Clinica Ferrara Which clinical scenario have to face First line therapy with today? Untreated metastatic breast

More information

Immunoconjugates in Both the Adjuvant and Metastatic Setting

Immunoconjugates in Both the Adjuvant and Metastatic Setting Immunoconjugates in Both the Adjuvant and Metastatic Setting Mark Pegram, M.D. Director, Stanford Breast Oncology Program Co-Director, Molecular Therapeutics Program Trastuzumab Treatment of Breast Tumor

More information

TRIALs of CDK4/6 inhibitor in women with hormone-receptor-positive metastatic breast cancer

TRIALs of CDK4/6 inhibitor in women with hormone-receptor-positive metastatic breast cancer TRIALs of CDK4/6 inhibitor in women with hormone-receptor-positive metastatic breast cancer Marta Bonotto Department of Oncology University Hospital of Udine TRIALs of CDK4/6 inhibitor in women with hormone-receptor-positive

More information

非臨床試験 臨床の立場から 京都大学医学部附属病院戸井雅和

非臨床試験 臨床の立場から 京都大学医学部附属病院戸井雅和 資料 2 2 非臨床試験 臨床の立場から 京都大学医学部附属病院戸井雅和 1 Preclinical studies Therapeutic Window: Efficacy/Toxicity Disease Specificity Subtype Specificity Combination: Concurrent/Sequential Therapeutic situation: Response/

More information

Targeted Agents In Breast Cancer. Wonderful Music With New Instruments

Targeted Agents In Breast Cancer. Wonderful Music With New Instruments Targeted Agents In Breast Cancer Wonderful Music With New Instruments 1 Trends In Cancer Mortality In Women in US At This Rate We Will Beat Breast Cancer In 2040 Is the cause screening?? Is the cause better

More information

Novel Preoperative Therapies for HER2-Positive Breast Cancer. Debu Tripathy, MD University of Southern California Norris Comprehensive Cancer Center

Novel Preoperative Therapies for HER2-Positive Breast Cancer. Debu Tripathy, MD University of Southern California Norris Comprehensive Cancer Center Novel Preoperative Therapies for HER2-Positive Breast Cancer Debu Tripathy, MD University of Southern California Norris Comprehensive Cancer Center Key Findings to Date in the Neoadjuvant Therapy of HER2+

More information

Review of adjuvant and neo-adjuvant abstracts from SABCS 2011 January 7 th 2012

Review of adjuvant and neo-adjuvant abstracts from SABCS 2011 January 7 th 2012 Review of adjuvant and neo-adjuvant abstracts from SABCS 2011 January 7 th 2012 Ruth M. O Regan, MD Professor and Vice-Chair for Educational Affairs, Department of Hematology and Medical Oncology, Emory

More information

What is new in HR+ Breast Cancer? Olivia Pagani Breast Unit and Institute of oncology of Southern Switzerland

What is new in HR+ Breast Cancer? Olivia Pagani Breast Unit and Institute of oncology of Southern Switzerland What is new in HR+ Breast Cancer? Olivia Pagani Breast Unit and Institute of oncology of Southern Switzerland Outline Early breast cancer Advanced breast cancer Open questions Outline Early breast cancer

More information

ENFERMEDAD AVANZADA Qué hacemos con el triple negativo? Nuevas aproximaciones

ENFERMEDAD AVANZADA Qué hacemos con el triple negativo? Nuevas aproximaciones ENFERMEDAD AVANZADA Qué hacemos con el triple negativo? Nuevas aproximaciones Javier Cortes, Hospital Universitario Ramon y Cajal, Madrid Vall d Hebron Institute of Oncology (VHIO), Barcelona Triple Negative

More information

The next wave of successful drug therapy strategies in HER2-positive breast cancer. Hans Wildiers University Hospitals Leuven Belgium

The next wave of successful drug therapy strategies in HER2-positive breast cancer. Hans Wildiers University Hospitals Leuven Belgium The next wave of successful drug therapy strategies in HER2-positive breast cancer Hans Wildiers University Hospitals Leuven Belgium Trastuzumab in 1st Line significantly improved the prognosis of HER2-positive

More information

Kazuhiro Araki, Yasuo Miyoshi

Kazuhiro Araki, Yasuo Miyoshi Editorial Abundant options to avoid toxicity and alternative strategies for human epidermal growth factor receptor 2-positive and hormone receptor-positive advanced breast cancer Kazuhiro Araki, Yasuo

More information

Lo studio BOLERO-1 Quali potranno essere le future ricadute nella pratica clinica? Antonella Ferro UO Oncologia Medica Trento

Lo studio BOLERO-1 Quali potranno essere le future ricadute nella pratica clinica? Antonella Ferro UO Oncologia Medica Trento Lo studio BOLERO-1 Quali potranno essere le future ricadute nella pratica clinica? Antonella Ferro UO Oncologia Medica Trento TRASTUZUMAB most important breakthrough in the management of BC Trastuzumab

More information

Breast Cancer Carcinogenesis: Mechanisms and Pathways in Hormone Receptor Positive Disease

Breast Cancer Carcinogenesis: Mechanisms and Pathways in Hormone Receptor Positive Disease Breast Cancer Carcinogenesis: Mechanisms and Pathways in Hormone Receptor Positive Disease 1 Nearly Two-Thirds of Metastatic Breast Cancers Express Hormone Receptors Breast cancer tumors are often classified

More information

Dennis J Slamon, MD, PhD

Dennis J Slamon, MD, PhD I N T E R V I E W Dennis J Slamon, MD, PhD Dr Slamon is Professor of Medicine, Chief of the Division of Hematology/Oncology and Director of Clinical and Translational Research at UCLA s David Geffen School

More information

New Drug Development in HER2+ Breast Cancer

New Drug Development in HER2+ Breast Cancer New Drug Development in HER2+ Breast Cancer Philippe Aftimos, M.D. Senior Research Physician Clinical Pharmacology Unit Institut Jules Bordet Background Amplification of HER2 occurs in approximately 20%

More information

Her 2 Positive Metastatic Breast Cancer

Her 2 Positive Metastatic Breast Cancer Her 2 Positive Metastatic Breast Cancer Alison Jones November 2013 Mrs Hermione Positive (then and now!) Diagnosed 2007 T2 N1 Mo ER ve; Her2 ve Mastectomy ANC; FEC/T Herceptin (12months) August 2010metastatic

More information

Targeting CDK 4/6. Jee Hyun Kim, M.D., Ph.D. Seoul National University College of Medicine

Targeting CDK 4/6. Jee Hyun Kim, M.D., Ph.D. Seoul National University College of Medicine 2016.04.30 GBCC Education Symposium Targeting CDK 4/6 Jee Hyun Kim, M.D., Ph.D. Seoul National University College of Medicine Contents Cyclins -CDKs in cell cycle control CDK 4/6 in breast cancer Preclinical

More information

Updates From San Antonio Breast Cancer Symposium 2017

Updates From San Antonio Breast Cancer Symposium 2017 Updates From San Antonio Breast Cancer Symposium 2017 Rob Coleman University of Sheffield Presentation Outline New Insights into adjuvant endocrine treatment Duration of treatment Perioperative therapy

More information

Sesiones interhospitalarias de cáncer de mama. Revisión bibliográfica 4º trimestre 2015

Sesiones interhospitalarias de cáncer de mama. Revisión bibliográfica 4º trimestre 2015 Sesiones interhospitalarias de cáncer de mama Revisión bibliográfica 4º trimestre 2015 Selected papers Prospective Validation of a 21-Gene Expression Assay in Breast Cancer TAILORx. NEJM 2015 OS for fulvestrant

More information

MEDICAL ONCOLOGY NEWS IN BREAST CANCER 2014

MEDICAL ONCOLOGY NEWS IN BREAST CANCER 2014 MEDICAL ONCOLOGY NEWS IN BREAST CANCER 2014 Dr Thomas Yau Clinical Assistant Professor MBBS(HK), MRCP (UK), FHKCP (Med Onc), FHKAM( Medicine), FRCP(London) Queen Mary Hospital The University of Hong Kong

More information

José Baselga, MD, PhD

José Baselga, MD, PhD i n t e r v i e w José Baselga, MD, PhD Dr Baselga is Physician-in-Chief at Memorial Sloan-Kettering Cancer Center in New York, New York. Tracks 1-15 Track 1 Track 2 Track 3 Track 4 Track 5 Track 6 Track

More information

Systemic Therapy of HER2-positive Breast Cancer

Systemic Therapy of HER2-positive Breast Cancer Systemic Therapy of HER2-positive Breast Cancer Tanja Cufer, MD, PhD University Clinic Golnik, Medical Faculty Ljubljana, Slovenia ESO ESMO Masterclass, Belgrade 2017 Relative Risk HER2-positive Breast

More information

Nuovo paradigma terapeutico nel trattamento del carcinoma mammario HER2+ metastatico: dagli studi alla pratica clinica Prima linea di trattamento

Nuovo paradigma terapeutico nel trattamento del carcinoma mammario HER2+ metastatico: dagli studi alla pratica clinica Prima linea di trattamento Nuovo paradigma terapeutico nel trattamento del carcinoma mammario HER2+ metastatico: dagli studi alla pratica clinica Prima linea di trattamento Prof. Sabino De Placido Dip. di Endocrinologia ed Oncologia

More information

Karcinom dojke. PANEL: Semir Bešlija, Zdenka Gojković, Robert Šeparović, Tajana Silovski

Karcinom dojke. PANEL: Semir Bešlija, Zdenka Gojković, Robert Šeparović, Tajana Silovski Karcinom dojke PANEL: Semir Bešlija, Zdenka Gojković, Robert Šeparović, Tajana Silovski MBC: HER2 PHEREXA: Study Design Multicenter, randomized, open-label phase III trial Stratified by prior CNS disease,

More information

pan-canadian Oncology Drug Review Final Clinical Guidance Report Everolimus (Afinitor) for Advanced Breast Cancer March 25, 2013

pan-canadian Oncology Drug Review Final Clinical Guidance Report Everolimus (Afinitor) for Advanced Breast Cancer March 25, 2013 pan-canadian Oncology Drug Review Final Clinical Guidance Report Everolimus (Afinitor) for Advanced Breast Cancer March 25, 2013 DISCLAIMER Not a Substitute for Professional Advice This report is primarily

More information

Update in the treatment of Her2- overexpressing breast cancers. Fabrice ANDRE Institut Gustave Roussy Villejuif, France

Update in the treatment of Her2- overexpressing breast cancers. Fabrice ANDRE Institut Gustave Roussy Villejuif, France Update in the treatment of Her2- overexpressing breast cancers Fabrice ANDRE Institut Gustave Roussy Villejuif, France Questions Should tumors

More information

Emerging Advances in Metastatic Breast Cancer

Emerging Advances in Metastatic Breast Cancer Emerging Advances in Metastatic Breast Cancer Bryan P. Schneider, MD Assistant Professor of Medicine & Medical Molecular Genetics IU Simon Cancer Center AT LEAST THREE types of breast cancer TNBC HER2+

More information

Present and emerging treatment options in Her-2/neu overexpressing metastatic breast cancer

Present and emerging treatment options in Her-2/neu overexpressing metastatic breast cancer Present and emerging treatment options in Her-2/neu overexpressing metastatic breast cancer Christoph C. Zielinski Clinical Division of Oncology, Department of Medicine I and Comprehensive Cancer Center,

More information

Triple Negative Breast Cancer. Eric P. Winer, MD Dana-Farber Cancer Institute Harvard Medical School Boston, MA October, 2008

Triple Negative Breast Cancer. Eric P. Winer, MD Dana-Farber Cancer Institute Harvard Medical School Boston, MA October, 2008 Triple Negative Breast Cancer Eric P. Winer, MD Dana-Farber Cancer Institute Harvard Medical School Boston, MA October, 2008 Triple Negative Breast Cancer 15% 25% Triple Negative 20% HER2+ ER+ Low Grade

More information

The following slides are provided as presented by the author during the live educa7onal ac7vity and are intended for reference purposes only.

The following slides are provided as presented by the author during the live educa7onal ac7vity and are intended for reference purposes only. The following slides are provided as presented by the author during the live educa7onal ac7vity and are intended for reference purposes only. If you have any ques7ons, please contact Imedex via email at:

More information

Endocrine treatment might NOT be the preferred option in Hrpos MBC. Dr. Mircea Dediu Sanador Hospital Bucharest Summer School Bucharest 2015

Endocrine treatment might NOT be the preferred option in Hrpos MBC. Dr. Mircea Dediu Sanador Hospital Bucharest Summer School Bucharest 2015 Endocrine treatment might NOT be the preferred option in Hrpos MBC Dr. Mircea Dediu Sanador Hospital Bucharest Summer School Bucharest 2015 Overall survival not improved by the AI treatment Benefit in

More information

K-Ras signalling in NSCLC

K-Ras signalling in NSCLC Targeting the Ras-Raf-Mek-Erk pathway Egbert F. Smit MD PhD Dept. Pulmonary Diseases Vrije Universiteit VU Medical Centre Amsterdam, The Netherlands K-Ras signalling in NSCLC Sun et al. Nature Rev. Cancer

More information

New Targeted Agents Demonstrate Greater Efficacy and Tolerability in the Treatment of HER2-positive Breast Cancer

New Targeted Agents Demonstrate Greater Efficacy and Tolerability in the Treatment of HER2-positive Breast Cancer New Evidence reports on presentations given at ASCO 2012 New Targeted Agents Demonstrate Greater Efficacy and Tolerability in the Treatment of HER2-positive Breast Cancer Presentations at ASCO 2012 Breast

More information

Manejo do câncer de mama RH+ na adjuvância: o que há de novo?

Manejo do câncer de mama RH+ na adjuvância: o que há de novo? II Simpósio Internacional de Câncer de Mama para o Oncologista Clínico Manejo do câncer de mama RH+ na adjuvância: o que há de novo? INGRID A. MAYER, MD, MSCI Assistant Professor of Medicine Director,

More information

Systemic Management of Breast Cancer

Systemic Management of Breast Cancer Systemic Management of Breast Cancer Why Who When What How long Etc. Vernon Harvey Rotorua, June 2014 Systemic Management of Breast Cancer Metastatic Disease Adjuvant Therapy Aims of therapy Quality of

More information

Lapatinib plus Letrozole as First-Line Therapy for HER-2 Hormone Receptor Positive Metastatic Breast Cancer

Lapatinib plus Letrozole as First-Line Therapy for HER-2 Hormone Receptor Positive Metastatic Breast Cancer The Oncologist Academia Pharma Intersect: Breast Cancer Lapatinib plus Letrozole as First-Line Therapy for HER-2 Hormone Receptor Positive Metastatic Breast Cancer LEE S. SCHWARTZBERG, a SANDRA X. FRANCO,

More information

7/6/2015. Cancer Related Deaths: United States. Management of NSCLC TODAY. Emerging mutations as predictive biomarkers in lung cancer: Overview

7/6/2015. Cancer Related Deaths: United States. Management of NSCLC TODAY. Emerging mutations as predictive biomarkers in lung cancer: Overview Emerging mutations as predictive biomarkers in lung cancer: Overview Kirtee Raparia, MD Assistant Professor of Pathology Cancer Related Deaths: United States Men Lung and bronchus 28% Prostate 10% Colon

More information

- ASCO ASCO. American Society of Clinical Oncology( VEGF( Vascular Endothelial Growth Factor) (angiogenesis) ASCO 2005

- ASCO ASCO. American Society of Clinical Oncology( VEGF( Vascular Endothelial Growth Factor) (angiogenesis) ASCO 2005 2005 5 24 () - ASC2005 - twatanab@oncoloplan.com / http://www.oncoloplan.com ASC American Society of Clinical ncology( ) 412005 5 13 17 3 5000 ASC 2005 bevacizumab / trastuzumab / mab monoclonal antibody

More information

Sustained benefits for women with HER2-positive early breast cancer JORGE MADRID BIG GOCCHI PROTOCOLO HERA

Sustained benefits for women with HER2-positive early breast cancer JORGE MADRID BIG GOCCHI PROTOCOLO HERA Sustained benefits for women with HER2-positive early breast cancer JORGE MADRID BIG GOCCHI PROTOCOLO HERA The fascinating history of Herceptin 1981 1985 1987 1990 1992 1998 2000 2005 2006 2008 2011 Murine

More information

Biomarkers for HER2-directed Therapies : Past Failures and Future Perspectives

Biomarkers for HER2-directed Therapies : Past Failures and Future Perspectives Biomarkers for HER2-directed Therapies : Past Failures and Future Perspectives Ian Krop Dana-Farber Cancer Institute Harvard Medical School Inchon 2018 Adjuvant Trastuzumab Improves Outcomes in HER2+ Breast

More information

Metastatic Breast Cancer What is new? Subtypes and variation?

Metastatic Breast Cancer What is new? Subtypes and variation? Metastatic Breast Cancer What is new? Subtypes and variation? Anne Blaes, MD, MS University of Minnesota, Division of Hematology/Oncology Director, Adult Cancer Survivor Program Current estimates for metastatic

More information

The PI3K/AKT axis. Dr. Lucio Crinò Medical Oncology Division Azienda Ospedaliera-Perugia. Introduction

The PI3K/AKT axis. Dr. Lucio Crinò Medical Oncology Division Azienda Ospedaliera-Perugia. Introduction The PI3K/AKT axis Dr. Lucio Crinò Medical Oncology Division Azienda Ospedaliera-Perugia Introduction Phosphoinositide 3-kinase (PI3K) pathway are a family of lipid kinases discovered in 1980s. They have

More information

Targeting mtor pathway in ER+/Her2- breast cancers. Fabrice ANDRE Gustave Roussy

Targeting mtor pathway in ER+/Her2- breast cancers. Fabrice ANDRE Gustave Roussy Targeting mtor pathway in ER+/Her2- breast cancers Fabrice ANDRE Gustave Roussy Outline mtor pathway Clinical development of rapalogs in breast cancer Moving beyond rapalogs mtor pathway LKB1 Ras-raf-

More information

Radiation therapy Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. Chemotherapy Chemotherapy is a cancer

More information

DR LUIS MANSO UNIDAD TUMORES DE MAMA Y GINECOLÓGICOS HOSPITAL 12 DE OCTUBRE MADRID

DR LUIS MANSO UNIDAD TUMORES DE MAMA Y GINECOLÓGICOS HOSPITAL 12 DE OCTUBRE MADRID DR LUIS MANSO UNIDAD TUMORES DE MAMA Y GINECOLÓGICOS HOSPITAL 12 DE OCTUBRE MADRID RESUMEN DE ARTICULOS THERESA BOLERO 3 NOAH UP-DATE GEPAR SIXTO RADIOTHERAPY EBCTCG CTCs MISCELANEAS Lancet Oncol 2014;

More information

2 nd line Therapy and Beyond NSCLC. Alan Sandler, M.D. Oregon Health & Science University

2 nd line Therapy and Beyond NSCLC. Alan Sandler, M.D. Oregon Health & Science University 2 nd line Therapy and Beyond NSCLC Alan Sandler, M.D. Oregon Health & Science University Treatment options for advanced or metastatic (stage IIIb/IV) NSCLC Suitable for chemotherapy Diagnosis Unsuitable/unwilling

More information

RIBOCICLIB EN PRIMERA LINEA DE TRATAMIENTO. Dra. Elena Aguirre H.U. Miguel Servet

RIBOCICLIB EN PRIMERA LINEA DE TRATAMIENTO. Dra. Elena Aguirre H.U. Miguel Servet RIBOCICLIB EN PRIMERA LINEA DE TRATAMIENTO Dra. Elena Aguirre H.U. Miguel Servet INTRODUCTION ADVANCED BREAST CANCER HR+/HER2- YES Consider Chemo VISCERAL CRISIS? NO Endocrine Therapy X3 Toxicity Progresive

More information

Predicting outcome in metastatic breast cancer

Predicting outcome in metastatic breast cancer Predicting outcome in metastatic breast cancer Aleix Prat, MD, PhD Medical Oncology Department Translational Genomics and Targeted Therapeutics in Solid Tumors Monday, 15 th January, Manchester, UK Disclosures

More information

C. Bourgier, I. Ray-Coquard, J. Provencal, C. Cropet, A.V. Bourcier, V. Delecroix, A. Reynaud-Bougnoux, J. Cretin, T. Bachelot

C. Bourgier, I. Ray-Coquard, J. Provencal, C. Cropet, A.V. Bourcier, V. Delecroix, A. Reynaud-Bougnoux, J. Cretin, T. Bachelot 1 Exploratory Subgroup Analysis of the TAMRAD Phase 2 GINECO Trial Evaluating Tamoxifen (TAM) Plus Everolimus (RAD) vs TAM Alone in Patients With Hormone-Receptor Positive, HER2-Negative Metastatic Breast

More information

Endocrine Therapy of Metastatic Breast Cancer

Endocrine Therapy of Metastatic Breast Cancer Diagnosis and Treatment of Patients with Primary and Metastatic Breast Cancer Endocrine Therapy of Metastatic Breast Cancer Endocrine Therapy of Metastatic Breast Cancer Version 2002: Gerber / Friedrichs

More information

Cancer du sein métastatique et amélioration de la survie Pr. X. Pivot

Cancer du sein métastatique et amélioration de la survie Pr. X. Pivot Cancer du sein métastatique et amélioration de la survie Pr. X. Pivot Date of preparation: November 2015. EU0250i TTP/PFS Comparaisons First line metastatic breast cancer Monotherapy Docetaxel Chan 1999

More information

Kevin R. Fox, MD Rena Rowan Breast Center Abramson Cancer Center University of Pennsylvania Perelman School of MedicineR

Kevin R. Fox, MD Rena Rowan Breast Center Abramson Cancer Center University of Pennsylvania Perelman School of MedicineR Kevin R. Fox, MD Rena Rowan Breast Center Abramson Cancer Center University of Pennsylvania Perelman School of MedicineR Treatment of early stage, HER2 positive breast cancer Treatment of early stage,

More information

Breast Cancer: ASCO Poster Review

Breast Cancer: ASCO Poster Review Breast Cancer: ASCO Poster Review Carmen Criscitiello, MD, PhD Istituto Europeo di Oncologia Milano HER2+ SUBTYPE Research questions in early HER2+ BC De-escalation of toxicity without compromising efficacy

More information

Concise Reference. HER2 Testing in Breast Cancer. Mary Falzon, Angelica Fasolo, Michael Gandy, Luca Gianni & Stefania Zambelli

Concise Reference. HER2 Testing in Breast Cancer. Mary Falzon, Angelica Fasolo, Michael Gandy, Luca Gianni & Stefania Zambelli Concise Reference Testing in Breast Cancer Mary Falzon, Angelica Fasolo, Michael Gandy, Luca Gianni & Stefania Zambelli Extracted from Handbook of -Targeted Agents in Breast Cancer ublished by Springer

More information