Chemoresistance: Detectors to Dormancy
|
|
|
- Arron Sutton
- 5 years ago
- Views:
Transcription
1 Chemoresistance: Detectors to Dormancy Andy Redfern University of Western Australia Harry Perkins Institute of Medical Research Fiona Stanley Hospital
2 Ongoing Projects: What to pack?
3 The Route to Efficacy Indication Prescription Drug Administration Metabolism Biodistribution Cancer Cell
4 The Route to Efficacy Indication Prescription Cancer Cell Uptake & Retention Drug Administration Target Interaction Metabolism Biodistribution Cancer Cell Critical Biochange Cell Damage Cell Death
5 C11-Orf67 Chemo-related Driver Pathways Active Apoptosis Mechanisms Chemosensitive Phenotype Drug Uptake and Retention Active Proliferation
6 Chemo-related Driver Pathways Topoisomerase II & Anthracyclines DiLeo et al Nov;12(12):
7 Chemo-related Driver Pathways Integrated Clusters: To Each Their Own Integrated Cluster 2 High risk ER positive cancers characterised by a chromosome11 amplification. Central to this is orf67,a gene coding for a small protein of unknown function Curtis et al. Nature (7403):
8 C11-Orf67 - Metabolism and Biosynthesis Nodes
9 C11-Orf67 - Metabolism and Biosynthesis Nodes C11Orf67 leads to upregulation of: MTHFD1L - an enzyme involved in tetrahydofolate synthesis and consequently purine and pyrimidine metabolism in mitochondria. ALDH1L2 - a mitochondrial isoform enzyme that converts 10- formyltetrahydrofolate to tetrahydrofolate Expression of the mitochondrial glycine biosynthesis pathway is associated with mortality in breast cancer patients. Jain et al. Science May 25; 336(6084):
10 C11-Orf67 - Metabolism and Biosynthesis Nodes This raises the question as to whether CMF should form part of the ideal adjuvant treatment for these tumours and whether other anti-folate strategies might be employed.
11 Fluorouracil: Differential Sensitivity and Estrogen Receptor Status
12 C11-Orf67 Chemo-related Driver Pathways Active Apoptosis Mechanisms Chemosensitive Phenotype Drug Uptake and Retention Active Proliferation BMP4
13 Drug Uptake and Retention ATP Binding Cassette Proteins Better Out Than In
14 Locking the Stable Door: Needs the Right Key Local Bladder Ca Local Dox Small Cell Lung Ca - CAV P = 0.290
15 Drug Uptake and Retention The BMP - TGFb Axis
16 Drug Uptake and Retention The BMP - TGFb Axis
17 Drug Uptake and Retention The BMP - TGFb Axis
18 BMP4 Suppresses Metastasis in Breast Cancer Xenographs P<0.01 Effect of BMP4 expression on primary tumour growth in 4T1.2 tumour bearing mice Survival Impact of BMP4 expression on 4T1.2 tumour bearing mice (p<0.001) (p=0.041) Effect of BMP4 expression on rate of distant metastasis in 4T1.2 tumour bearing mice Treatment of 4T1.2 tumour bearing mice with rbmp4 (200ng, twice daily) Cao et al. Cancer Res; 74(18) September 15, 2014.
19 ABCG2 expression (mrna) (Arbitary units) NF-kB activity ABCG1 expression (mrna) (Arbitary units) % of living cells BMP4 Induces ABC Protein Synthesis and Chemosensitivity P<0.05 P<0.001 P<0.01 4T1.2 4T1.2 -BMP4 4T1.2 4T1.2 -BMP4 4T1.2 rbmp4 P<0.01 P<0.01 4T1.2 4T1.2 BMP4 4T1.2 BMP4 4T1.2
20 Metastasis-free survival (%) BMP4 Correlates with Improved Outcome In Unselected Patients HR=0.59, p=0.12 Months from Dx Breast cancer specific survival BMP4 positive HR 0.54, Chi-sq p = 0.048
21 C11-Orf67 Chemo-related Driver Pathways PKR Active Apoptosis Mechanisms Chemosensitive Phenotype Drug Uptake and Retention Active Proliferation BMP4
22 Apoptosis Modulation
23 Project : Active Apoptosis Mechanisms Protein Kinase RNA Activated: Toxin-Triggerman Kinase RNA Binding PKR Activation PKR Inhibition Redfern et al PNAS 110(16):
24 Project : Active Apoptosis Mechanisms Protein Kinase RNA Activated: Toxin-Triggerman - EIF2a Protein Synthesis Inhibition Cell Death
25 Project : PKR Associated with Higher DFS and OS After Adjuvant Chemotherapy for Early Breast Cancer 100 Disease-free survival survival (%) (%) HR=0.25, p=0.02 PKR Negative PKR Positive PACT negative PACT positive Time from diagnosis (years)
26 % with clinical benefit Project : PKR Associated with Higher Response Rate to Chemotherapy Metastatic Patients Given Chemotherapy: All Types P=0.10 P= PACT PKR
27 Project : Active Apoptosis Mechanisms PACT: Sensitising Mouse Fibroblasts to Anthracyclines FLAG-EV FLAG-PACT Mitomycin C (ng/ml) Bennett et al Blood, 108(3):
28 C11-Orf67 Chemo-related Driver Pathways PKR Active Apoptosis Mechanisms - Chemosensitive Phenotype ER Signalling Drug Uptake and Retention Active Proliferation BMP4
29 Apoptosis Resistance
30 Bcl-2 relative mrna level Project : Active Apoptosis Mechanisms Estrogen Signalling and Chemoresistance Comparison of Bcl-2 Immunoreactivity and ER/PR Status in Breast Cancer Clinical Specimens Impact of Anti-estrogens on Bcl-2 Expression in Breast Cancer Cell Line MCF7 fulvestrant tamoxifen Bhargava et al. Am J Path 145(3) 1994 Diel et al. Breast Cancer Res Treat 58:
31 Combination Index Combination Index Project : Active Apoptosis Mechanisms Estrogen Signalling and Chemoresistance Effects of combination treatments with Anti-estrogens and Cytotoxics on Breast Cancer Cells Doxorubicin Docetaxel fulvestrant tamoxifen OH-tamoxifen >1 antagonism <1 synergism Fraction affected Fraction affected Adjuvant Sequential v Concurrent Chemotherapy and Tamoxifen: The INT-0100 Study Disease-free Survival: HR 0.84, p=0.055 Overall Survival: HR 0.83, p=0.043 Ikeda et al. Cancer Sci (11): Albain et al. Lancet ,
32 Project : Active Apoptosis Mechanisms Aromatase Inhibition and Chemoresistance The efficacy and safety of neoadjuvant chemotherapy /- letrozole in postmenopausal women with locally advanced breast cancer: a randomized phase III clinical trial. Responses (%) Chemo-AI Chemo p value ELIMINATE: Randomised phase II trial of neoadjuvant chemotherapy /- concurrent aromatase inhibitor endocrine therapy to down-stage large oestrogen receptor positive breast cancer. Mohammadianpanah et al. Breast Cancer Res Treat Apr;132(3):853-61
33 Active Apoptosis Mechanisms ELIMINATE: Translational Studies Anti-Estrogen Action: Cell cycle Anti-Estrogen Action: Apoptosis Adapted from Musgrove and Sutherland. Nat Rev Cancer Sep;9(9):631-43
34 Active Apoptosis Mechanisms ELIMINATE: Translational Studies Proliferation Apoptosis
35 C11-Orf67 Chemo-related Driver Pathways TR-b Chemosensitive Phenotype PKR Active Apoptosis Mechanisms - ER Signalling Drug Uptake and Retention BMP4 Active Proliferation
36 Active Apoptosis Mechanisms Thyroid Receptors and Apoptosis
37 Active Apoptosis Mechanisms Thyroid Receptors and Apoptosis
38 Active Apoptosis Mechanisms Thyroid Receptors and Apoptosis TRb knockdown sensitises triple negative breast tumour cells to chemotherapeutics. Trb agonists increase docetaxelinduced apoptosis (evidenced by cleaved PARP)
39 C11-Orf67 PKR Chemo-related Driver Pathways TR-b Active Apoptosis Mechanisms - Chemosensitive Phenotype ER Signalling Drug Uptake and Retention - EMT - Active Proliferation BMP4
40 Epithelial Mesenchymal Transition
41 Epithelial Mesenchymal Transition EMT Staining: CK19 - Vimentin Co-expression Co-expression (mag) Cytokeratin 19 Vimentin DAPI
42 Epithelial Mesenchymal Transition EMT Presence Before Neoadjuvant Chemotherapy: Influence on Outcome N pcr Relapse 5 yr BrC death 5yr Any relapse Any BrC death EMT Absent EMT Present Chi-sq p
43 Epithelial Mesenchymal Transition EMT Presence After Neoadjuvant Chemotherapy: Influence on Outcome N pcr Relapse 5 yr BrC death 5yr Any relapse Any BrC death EMT Absent 8 NA EMT Present 9 NA Chi-sq p No EMT EMT
44 Epithelial Mesenchymal Transition Precedent for Differing Phenotypes Within Epithelial Mesenchymal Transitioned Breast Cancer Cells
45 Epithelial Mesenchymal Transition Potential Mechanisms of Chemoresistance Arising from Epithelial Mesenchymal Transition: MDR Induction
46 C11-Orf67 PKR Chemo-related Driver Pathways TR-b Active Apoptosis Mechanisms - Chemosensitive Phenotype ER Signalling Drug Uptake and Retention BMP4 - EMT Dense Collagen - Active Proliferation
47 Dormancy: The Sleeping Giant Epithelial Mesenchymal Transition Dense Collagen, EMT and Dormancy
48 Proliferation Epithelial Mesenchymal Transition Dense Collagen, EMT and Dormancy Proliferation with Collagen Density Laser capture and PCR expression analysis of single primary tumour cells v intratumoural cells p27 knockdown reverses the SPC state Raviraj et al. Clin Exp Metastasis (2012) 29:
49 Epithelial Mesenchymal Transition Impacts on Chemoresistance & Local Relapse Intra-tumour Cells P<0.01 Single Primary Cells DMSO 10um 100um DMSO 10um 100um P<0.01
50 C11-Orf67 PKR Chemo-related Driver Pathways TR-b Active Apoptosis Mechanisms - Chemosensitive Phenotype ER Signalling Drug Uptake and Retention BMP4 - Notch EMT Dense Collagen - Active Proliferation
51 Epithelial Mesenchymal Transition Impact of Notch Pathway Activity on Chemoresistance Indigenous outcomes Meng et al. Cancer Res 2009;69:
52 Epithelial Mesenchymal Transition Impact of Notch Pathway Activity on Chemoresistance Candy et al. British Journal of Cancer (2013) 109,
53 Epithelial Mesenchymal Transition Impact of Notch Pathway Activity on Chemoresistance A validation study repeating this analysis in an independent cohort will also look at correlations between NOTCH signalling and EMT.
54 C11-Orf67 How to Translate to Clinical Care? PKR Chemo-related Driver Pathways TR-b Active Apoptosis Mechanisms - Chemosensitive Phenotype ER Signalling Drug Uptake and Retention - Notch EMT Dense Collagen - Active Proliferation BMP4
55 Anti- Metabolites C11-Orf67 How to Translate to Clinical Care? PKR?TRBP KD Chemo-related Driver Pathways Thyroid Hormone Analogues TR-b Active Apoptosis Mechanisms - Chemosensitive Phenotype ER Signalling Estrogen Receptor Antagonists Drug Uptake and Retention - Gamma Secretase Inhibitors Notch EMT Salinomycin Etoposide - Tribble1 Dense manipulation Collagen Active Proliferation rbmp4 BMP4
56 Enoughs Enough
57 Summary A number of native and induced biological mechanisms exist that may contribute to chemoresistance. Many are potentially exploitable to enhance therapeutic outcomes. Certain phenotypes may render the tumour sensitive to certain chemotherapies C11Orf67 for anti-metabolites shows promise. Reactivating apoptotic potential through triggering (eg PKR) or effector mechanisms (eg Bcl2 inhibition through ER blockade) may prove effective. Multidrug resistance targeting has not yet proven effective. Mechanisms controlling expression rather than function (eg BMP4) may meet with more success. EMT triggers and mechanisms are diverse with similarly diverse effects on outcome. Screen-identified agents with efficacy against mesenchymally shifted cells (eg salinomycin, etoposide) could add efficacy to current treatments. Study of EMT arising as a result of chemotherapy exposure, dense breast tissue, NOTCH signalling or other stimuli may yield alternative routes to target the mesenchymal state.
58 Acknowledgements A/Prof Pilar Blancafort, Harry Perkins Institute C11 Orf67 Prof Robin Anderson, Peter MacCallum Centre BMP4 Prof Peter Leedman, Harry Perkins TRb, PKR, NOTCH A/Prof Lilian Soon, University of Sydney SPCs, Tribble1 Prof Rik Thompson, Queensland Uni of Tech Empathy
Adjuvant Systemic Therapy in Early Stage Breast Cancer
Adjuvant Systemic Therapy in Early Stage Breast Cancer Julie R. Gralow, M.D. Director, Breast Medical Oncology Jill Bennett Endowed Professor of Breast Cancer Professor, Global Health University of Washington
Mdi Medical Management of Breast Cancer Morbidity and Mortality Aug 13, 2009 Irina Kovatch, PGY3 Introduction Metastatic disease is the principal cause of death from breast cancer Metastatic events often
Intro to Cancer Therapeutics
An Intro to Cancer Therapeutics Christopher R. Chitambar, MD Professor of Medicine Division of Hematology & Oncology Froedtert and Medical College of Wisconsin Clinical Cancer Center cchitamb@mcw.edu Intro
Ideal neo-adjuvant Chemotherapy in breast ca. Dr Khanyile Department of Medical Oncology, University of Pretoria
Ideal neo-adjuvant Chemotherapy in breast ca Dr Khanyile Department of Medical Oncology, University of Pretoria When is neo-adjuvant Chemo required? Locally advanced breast ca: - Breast conservative surgery
Breast Cancer Breast Managed Clinical Network
Initial Evaluation Clinical Stage Pre-Treatment Evaluation Treatment and pathological stage Less than 4 positive lymph nodes Adjuvant Treatment ER Positive HER2 Negative (see page 2 & 3 ) HER2 Positive
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
Assessment of Risk Recurrence: Adjuvant Online, OncotypeDx & Mammaprint
Assessment of Risk Recurrence: Adjuvant Online, OncotypeDx & Mammaprint William J. Gradishar, MD Professor of Medicine Robert H. Lurie Comprehensive Cancer Center of Northwestern University Classical
Postoperative Adjuvant Chemotherapies. Stefan Aebi Luzerner Kantonsspital
Postoperative Adjuvant Chemotherapies Stefan Aebi Luzerner Kantonsspital stefan.aebi@onkologie.ch Does Chemotherapy Work in Older Patients? ER : Chemotherapy vs nil Age
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+
Use of Ovarian Suppression and Ablation in Breast Cancer Treatment
Use of Ovarian Suppression and Ablation in Breast Cancer Treatment Dr Marina Parton Consultant Medical Oncologist Royal Marsden and Kingston Hospitals Overview Breast cancer phenotypes Use of ovarian manipulation
Seigo Nakamura,M.D.,Ph.D.
Seigo Nakamura,M.D.,Ph.D. Professor of Surgery Director of Breast Center Showa University Hospital Chairman of the board of directors Japan Breast Cancer Society Inhibition of Estrogen-Dependent Growth
Treatment Options for Breast Cancer in Low- and Middle-Income Countries: Adjuvant and Metastatic Systemic Therapy
Women s Empowerment Cancer Advocacy Network (WE CAN) Conference Bucharest, Romania October 2015 Treatment Options for Breast Cancer in Low- and Middle-Income Countries: Adjuvant and Metastatic Systemic
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
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
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
Clinical Management Guideline for Breast Cancer
Initial Evaluation Clinical Stage Pre-Treatment Evaluation Treatment and pathological stage Adjuvant Treatment Less than 4 positive lymph nodes ER Positive HER2 Negative (see page 2 & 3 ) Primary Diagnosis:
The Three Ages of Systemic Adjuvant Therapy for EBC
The Three Ages of Systemic Adjuvant Therapy for EBC 1896-2018 Nicholas Wilcken Westmead Hospital Petersham Institute University of Sydney Questions to be answered (concentrating on chemotherapy) Why should
It is a malignancy originating from breast tissue
59 Breast cancer 1 It is a malignancy originating from breast tissue including both early stages which are potentially curable, and metastatic breast cancer (MBC) which is usually incurable. Most breast
The clinical relevance of circulating, cell-free and exosomal micrornas as biomarkers for gynecological tumors
Department of Tumor Biology The clinical relevance of circulating, cell-free and exosomal micrornas as biomarkers for gynecological tumors cfdna Copenhagen April 6-7, 2017 Heidi Schwarzenbach, PhD Tumor
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
Nadia Harbeck Breast Center University of Cologne, Germany
Evidence in Favor of Taxane Based Combinations and No Anthracycline in Adjuvant and Metastatic Settings Nadia Harbeck Breast Center University of Cologne, Germany Evidence in Favor of Taxane Based Combinations
Objectives Critically review presentations on 1. Local therapy 2. Adjuvant chemotherapy for isolated local regional recurrence 3. The optimal duration
Objectives Critically review presentations on 1. Local therapy 2. Adjuvant chemotherapy for isolated local regional recurrence 3. The optimal duration of endocrine therapy 4. Advances in HER2 directed
through the cell cycle. However, how we administer drugs also depends on the combinations that we give and the doses that we give.
Hello and welcome to this lecture. My name is Hillary Prescott. I am a Clinical Pharmacy Specialist at The University of Texas MD Anderson Cancer Center. My colleague, Jeff Bryan and I have prepared this
Gene Signatures in Breast Cancer: Moving Beyond ER, PR, and HER2? Lisa A. Carey, M.D. University of North Carolina USA
Gene Signatures in Breast Cancer: Moving Beyond ER, PR, and HER2? Lisa A. Carey, M.D. University of North Carolina USA When Are Biomarkers Ready To Use? Same Rules for Gene Expression Panels Key elements
Emerging Approaches for (Neo)Adjuvant Therapy for ER+ Breast Cancer
Emerging Approaches for (Neo)Adjuvant Therapy for E+ Breast Cancer Cynthia X. Ma, M.D., Ph.D. Associate Professor of Medicine Washington University in St. Louis Outline Current status of adjuvant endocrine
UK Interdisciplinary Breast Cancer Symposium. Should lobular phenotype be considered when deciding treatment? Michael J Kerin
UK Interdisciplinary Breast Cancer Symposium Should lobular phenotype be considered when deciding treatment? Michael J Kerin Professor of Surgery National University of Ireland, Galway and Galway University
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
8/8/2011. PONDERing the Need to TAILOR Adjuvant Chemotherapy in ER+ Node Positive Breast Cancer. Overview
Overview PONDERing the Need to TAILOR Adjuvant in ER+ Node Positive Breast Cancer Jennifer K. Litton, M.D. Assistant Professor The University of Texas M. D. Anderson Cancer Center Using multigene assay
Lecture 5. Primary systemic therapy: clinical and biological endpoints
Lecture 5 Primary systemic therapy: clinical and biological endpoints Valentina Guarneri, M.D., Ph.D. Primary systemic therapy in breast cancer Firstly introduced d into clinical i l practice in 70s for
Study Of Letrozole Extension. Coordinating Group IBCSG IBCSG BIG 1-07
tudy Of Letrozole Extension Coordinating Group IBCSG IBCSG 35-07 BIG 1-07 A phase III trial evaluating the role of continuous letrozole versus intermittent letrozole following 4 to 6 years of prior adjuvant
Harmesh Naik, MD. Hope Cancer Clinic
Harmesh Naik, MD. Hope Cancer Clinic A brief review of adjuvant therapy of breast cancer Summarize selected new developments in adjuvant therapy of breast cancer Discussion is limited to early stage breast
Chemotherapy-induced intestinal mucositis: The role of apoptosis regulators. Joanne M. Bowen BHSc(Hons)
Chemotherapy-induced intestinal mucositis: The role of apoptosis regulators. Joanne M. Bowen BHSc(Hons) Thesis submitted for degree of Doctor of Philosophy Department of Medicine The University of Adelaide
Systemic Treatment of Breast Cancer. Hormone Therapy and Chemotherapy, Curative and Palliative
Systemic Treatment of Breast Cancer Hormone Therapy and Chemotherapy, Curative and Palliative Systemic Therapy Invasive breast cancers Two forms Curative Palliative Curative Systemic Therapy Adjuvant Therapy
Luminal early breast cancer: (neo-) adjuvant endocrine therapy
CAMPUS GROSSHADERN CAMPUS INNENSTADT KLINIK UND POLIKLINIK FÜR FRAUENHEILKUNDE UND GEBURTSHILFE DIREKTOR: PROF. DR. MED. SVEN MAHNER Luminal early breast cancer: (neo-) adjuvant endocrine therapy Nadia
BREAST CANCER. Dawn Hershman, MD MS. Medicine and Epidemiology Co-Director, Breast Program HICCC Columbia University Medical Center.
BREAST CANCER Dawn Hershman, MD MS Florence Irving Assistant Professor of Medicine and Epidemiology Co-Director, Breast Program HICCC Columbia University Medical Center Background Breast cancer is the
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
Neoadjuvant therapy a new pathway to registration?
Neoadjuvant therapy a new pathway to registration? Graham Ross, FFPM Clinical Science Leader Roche Products Ltd Welwyn Garden City, UK (full time employee) Themes Neoadjuvant therapy Pathological Complete
Implications of Progesterone Receptor Status for the Biology and Prognosis of Breast Cancers
日大医誌 75 (1): 10 15 (2016) 10 Original Article Implications of Progesterone Receptor Status for the Biology and Prognosis of Breast Cancers Naotaka Uchida 1), Yasuki Matsui 1), Takeshi Notsu 1) and Manabu
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
Breast Cancer Risk and Disease Outcomes for Australian Aboriginal Women
Breast Cancer Risk and Disease Outcomes for Australian Aboriginal Women On the Agenda How frequent is breast cancer in the Indigenous population relative to non- Indigenous people. How do breast cancer
ATAC Trial. 10 year median follow-up data. Approval Code: AZT-ARIM-10005
ATAC Trial 10 year median follow-up data Approval Code: AZT-ARIM-10005 Background FDA post-approval commitment analysis to update DFS, TTR, OS and Safety Prof. Jack Cuzick on behalf of ATAC/LATTE Trialists
COME HOME Innovative Oncology Business Solutions, Inc.
Innovative Oncology Business Solutions, Inc. Breast Cancer Diagnostic/Therapeutic Pathway V11, April 2015 Required Structured Data Fields: ICD9 Code Stage Staging Components Performance Status Treatment
38 years old, premenopausal, had L+snbx. Pathology: IDC Gr.II T-1.9cm N+2/4sn ER+100%st, PR+60%st, Her2-neg, KI %
38 years old, premenopausal, had L+snbx Pathology: IDC Gr.II T-1.9cm N+2/4sn ER+100%st, PR+60%st, Her2-neg, KI67 5-10% Question: What will you do now? 1. Give adjuvant chemotherapy 2. Send for Oncotype
SYSTEMIC THERAPY OPTIONS FOR BREAST CANCER IN 2014
SYSTEMIC THERAPY OPTIONS FOR BREAST Oncology Day 2014 CANCER IN 2014 Dr. Katherine Enright, M.D., M.P.H., F.R.C.P.(C) Katherine.enright@Trilliumhealthpartners.ca OBJECTIVES 1. Outline an approach to the
SYSTEMIC TREATMENT OF TRIPLE NEGATIVE BREAST CANCER
SYSTEMIC TREATMENT OF TRIPLE NEGATIVE BREAST CANCER Sunil Shrestha 1*, Ji Yuan Yang, Li Shuang and Deepika Dhakal Clinical School of Medicine, Yangtze University, Jingzhou, Hubei Province, PR. China Department
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
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
Profili di espressione genica
Profili di espressione genica Giampaolo Bianchini MD Ospedale San Raffaele, Milan - Italy Gene expression profiles Transcriptomics Gene DNA mrna mirnas Protein metilation Metabolite Genomics Transcriptomics
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
Janet E. Dancey NCIC CTG NEW INVESTIGATOR CLINICAL TRIALS COURSE. August 9-12, 2011 Donald Gordon Centre, Queen s University, Kingston, Ontario
Janet E. Dancey NCIC CTG NEW INVESTIGATOR CLINICAL TRIALS COURSE August 9-12, 2011 Donald Gordon Centre, Queen s University, Kingston, Ontario Session: Correlative Studies in Phase III Trials Title: Design
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
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
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
Beyond the Guidelines: Clinical Investigators Provide Their Perspectives on Current Strategies and Ongoing Research in the Management of Breast Cancer
Beyond the Guidelines: Clinical Investigators Provide Their Perspectives on Current Strategies and Ongoing Research in the Management of Breast Cancer Wednesday, December 11, 2013 7:30 PM 9:30 PM San Antonio,
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
When is Chemotherapy indicated in Advanced Luminal Breast Cancer?
When is Chemotherapy indicated in Advanced Luminal Breast Cancer? Soo-Chin Lee Head & Senior Consultant Department of Haematology-Oncology Clinical Care National University Cancer Institute, Singapore
Rationale For & Design of TAILORx. Joseph A. Sparano, MD Albert Einstein College of Medicine Montefiore-Einstein Cancer Center Bronx, New York
Rationale For & Design of TAILORx Joseph A. Sparano, MD Albert Einstein College of Medicine Montefiore-Einstein Cancer Center Bronx, New York Declining Breast Cancer Mortality & Event Rates in Adjuvant
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
EARLY BREAST CANCER, HER2-POSITIVE
EARLY BREAST CANCER, HER2-POSITIVE CLINICAL CASE DISCUSSION Elżbieta Senkus Medical University of Gdańsk Gdańsk, Poland esmo.org DISCLOSURES Honoraria: Amgen, Astellas, AstraZeneca, Bayer, BMS, Celgene,
SUPPLEMENTARY INFORMATION
DOI: 10.1038/ncb2607 Figure S1 Elf5 loss promotes EMT in mammary epithelium while Elf5 overexpression inhibits TGFβ induced EMT. (a, c) Different confocal slices through the Z stack image. (b, d) 3D rendering
Extended Hormonal Therapy
Extended Hormonal Therapy Dr. Caroline Lohrisch, Medical Oncologist, BC Cancer Agency Vancouver Centre November 1, 2014 www.fpon.ca Optimal Endocrine Therapy for Women with Hormone Receptor Positive Early
Considerations in Adjuvant Chemotherapy. Joyce O Shaughnessy, MD Baylor Sammons Cancer Center Texas Oncology US Oncology
Considerations in Adjuvant Chemotherapy Joyce O Shaughnessy, MD Baylor Sammons Cancer Center Texas Oncology US Oncology 80 70 60 50 40 30 20 10 0 EBCTCG 2005/6 Overview Control Arms with No Systemic Treatment
NATIONAL INSTITUTE FOR HEALTH AND CLINICAL EXCELLENCE. Proposed Health Technology Appraisal
NATIONAL INSTITUTE FOR HEALTH AND CLINICAL EXCELLENCE Proposed Health Technology Appraisal Everolimus in combination with exemestane for the treatment of advanced or metastatic HER2 negative, oestrogen
Breast cancer. Prof Arlene Chan Medical Oncologist Director Breast Clinical Trials Unit, Mount Hospital Vice-Chair Breast Cancer Research Centre - WA
Breast cancer rof Arlene Chan Medical Oncologist Director Breast Clinical Trials Unit, Mount Hospital Vice-Chair Breast Cancer Research Centre - WA Breast cancer Incidence of Breast Cancer by Stage at
Johns Hopkins Clinical Update Webinar
Johns Hopkins Clinical Update Webinar Ben Ho Park, M.D., Ph.D. Department of Oncology Johns Hopkins University February 2015 This presentation is the intellectual property of the author/presenter. Contact
Anthracyclines for Breast Cancer? Are Adjuvant Anthracyclines Dispensible? Needs to be Answered in a Large Prospective Trial
Anthracyclines for Breast Cancer? Are Adjuvant Anthracyclines Dispensible? Needs to be Answered in a Large Prospective Trial Joanne L. Blum, MD, PhD Baylor-Sammons Cancer Dallas, TX Early Breast Cancer
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
TRANSPARENCY COMMITTEE OPINION. 15 February 2006
The legally binding text is the original French version TRANSPARENCY COMMITTEE OPINION 15 February 2006 Taxotere 20 mg, concentrate and solvent for solution for infusion B/1 vial of Taxotere and 1 vial
Breast cancer treatment
Report from the San Antonio Breast Cancer Symposium Breast cancer treatment Determining the best options for select patient groups Sara Soldera, MD, Resident; Nathaniel Bouganim, MD, FRCPC, Medical Oncologist;
Breast Cancer Earlier Disease. Stefan Aebi Luzerner Kantonsspital
Breast Cancer Earlier Disease Stefan Aebi Luzerner Kantonsspital stefan.aebi@onkologie.ch Switzerland Breast Cancer Earlier Disease Diagnosis and Prognosis Local Therapy Surgery Radiation therapy Adjuvant
Evolving Insights into Adjuvant Chemotherapy. Joyce O Shaughnessy, MD Baylor Sammons Cancer Center Texas Oncology US Oncology
Evolving Insights into Adjuvant Chemotherapy Joyce O Shaughnessy, MD Baylor Sammons Cancer Center Texas Oncology US Oncology 80 70 60 50 40 30 20 10 0 EBCTCG 2005/6 Overview Control Arms with No Systemic
Supplementary appendix
Supplementary appendix This appendix formed part of the original submission and has been peer reviewed. We post it as supplied by the authors. Supplement to: Cortazar P, Zhang L, Untch M, et al. Pathological
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,
Update on New Perspectives in Endocrine-Sensitive Breast Cancer. James R. Waisman, MD
Update on New Perspectives in Endocrine-Sensitive Breast Cancer James R. Waisman, MD Nothing to disclose DISCLOSURE TAILORx Oncotype Recurrence Score TAILORx Study Design Sparano, J Clin Oncol 2008;26:721-728
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
Clinical Oncology - Science in focus - Editorial. Understanding oestrogen receptor function in breast cancer, and its interaction with the
Clinical Oncology - Science in focus - Editorial TITLE: Understanding oestrogen receptor function in breast cancer, and its interaction with the progesterone receptor. New preclinical findings and their
Circulating Tumor Cells in non- Metastatic Triple Negative Breast Cancer
Circulating Tumor Cells in non- Metastatic Triple Negative Breast Cancer Carolyn Hall, Ph.D. Department of Surgical Oncology The University of Texas MD Anderson Cancer Center Triple Negative Breast Cancer
Award Number: W81XWH TITLE: Characterizing an EMT Signature in Breast Cancer. PRINCIPAL INVESTIGATOR: Melanie C.
AD Award Number: W81XWH-08-1-0306 TITLE: Characterizing an EMT Signature in Breast Cancer PRINCIPAL INVESTIGATOR: Melanie C. Bocanegra CONTRACTING ORGANIZATION: Leland Stanford Junior University Stanford,
Role of Genomic Profiling in (Minimally) Node Positive Breast Cancer
Role of Genomic Profiling in (Minimally) Node Positive Breast Cancer Kathy S. Albain, MD, FACP Professor of Medicine Dean s Scholar Loyola University Chicago Stritch School of Medicine Cardinal Bernardin
The Role of Pathologic Complete Response (pcr) as a Surrogate Marker for Outcomes in Breast Cancer: Where Are We Now?
1 The Role of Pathologic Complete Response (pcr) as a Surrogate Marker for Outcomes in Breast Cancer: Where Are We Now? Terry Mamounas, M.D., M.P.H., F.A.C.S. Medical Director, Comprehensive Breast Program
4/13/2010. Silverman, Buchanan Breast, 2003
Tailoring Breast Cancer Treatment: Has Personalized Medicine Arrived? Judith Luce, M.D. San Francisco General Hospital Avon Comprehensive Breast Care Center Outline First, treatment of DCIS Sorting risk
Choosing between different hormonal therapies. Rudy Van den Broecke UZ Ghent
Choosing between different hormonal therapies Rudy Van den Broecke UZ Ghent What is the golden standard in premenopausal hormonal sensitive early breast cancer? Ovarian Suppression alone 5 years Tamoxifen
Triple Negative Breast Cancer: Part 2 A Medical Update
Triple Negative Breast Cancer: Part 2 A Medical Update April 29, 2015 Tiffany A. Traina, MD Breast Medicine Service Memorial Sloan Kettering Cancer Center Weill Cornell Medical College Overview What is
Systemic Therapy for Locally Advanced Breast Cancer
Systemic Therapy for Locally Advanced Breast Cancer Soo-Chin Lee Head & Senior Consultant Department of Haematology-Oncology National University Cancer Institute, Singapore Clinical Care Senior Principal
Breast Cancer. Most common cancer among women in the US. 2nd leading cause of death in women. Mortality rates though have declined
Breast Cancer Most common cancer among women in the US 2nd leading cause of death in women Mortality rates though have declined 1 in 8 women will develop breast cancer Breast Cancer Breast cancer increases
Supplementary Online Content
Supplementary Online Content Spring LM, Gupta A, Reynolds KL, et al. Neoadjuvant endocrine therapy for estrogen receptor positive breast cancer: a systematic review and meta-analysis. JAMA Oncol. Published
A Layperson's Guide to Endocrine (Hormone) Therapy
A Layperson's Guide to Endocrine (Hormone) Therapy What we will cover What is the endocrine system Basic definition of endocrine therapy Classes of endocrine drugs How you can utilise endocrine therapy
Lessons Learnt from Neoadjuvant Hormone Therapy. 10 Lessons Learnt from Neoadjuvant Endocrine Therapy. Lesson 1
Lessons Learnt from Neoadjuvant Hormone Therapy Mike Dixon Clinical Director Breakthrough Research Unit Edinburgh 10 Lessons Learnt from Neoadjuvant Endocrine Therapy 10 Lessons Learnt from Neoadjuvant
Lessons Learnt from Neoadjuvant Hormone Therapy. Mike Dixon Clinical Director Breakthrough Research Unit Edinburgh
Lessons Learnt from Neoadjuvant Hormone Therapy Mike Dixon Clinical Director Breakthrough Research Unit Edinburgh 10 Lessons Learnt from Neoadjuvant Endocrine Therapy 10 Lessons Learnt from Neoadjuvant
Contemporary Classification of Breast Cancer
Contemporary Classification of Breast Cancer Laura C. Collins, M.D. Vice Chair of Anatomic Pathology Professor of Pathology Beth Israel Deaconess Medical Center and Harvard Medical School Boston, MA Outline
Molecular classification of breast cancer implications for pathologists. Sarah E Pinder
Molecular classification of breast cancer implications for pathologists Sarah E Pinder Courtesy of CW Elston Histological types Breast Cancer Special Types 17 morphological special types 25-30% of all
EARLY STAGE BREAST CANCER ADJUVANT CHEMOTHERAPY. Dr. Carlos Garbino
EARLY STAGE BREAST CANCER ADJUVANT CHEMOTHERAPY Dr. Carlos Garbino EARLY BREAST CANCER ADJUVANT CHEMOTHERAPY SUSTANTIVE DIFFICULTIES FOR A WORLDWIDE APPLICABILITY DUE TO IMPORTANT INEQUALITIES + IN DIFFERENT
Breast Cancer. Saima Saeed MD
Breast Cancer Saima Saeed MD Breast Cancer Most common cancer among women in the US 2nd leading cause of death in women 1 in 8 women will develop breast cancer Incidence/mortality rates have declined Breast
Impact of BMI on pathologic complete response (pcr) following neo adjuvant chemotherapy (NAC) for locally advanced breast cancer
Impact of BMI on pathologic complete response (pcr) following neo adjuvant chemotherapy (NAC) for locally advanced breast cancer Rachna Raman, MD, MS Fellow physician University of Iowa hospitals and clinics
10/15/2012. Inflammatory Breast Cancer vs. LABC: Different Biology yet Subtypes Exist
Triple-Negative Breast Cancer: Optimizing Treatment for Locally Advanced Breast Cancer Beth Overmoyer MD Director, Inflammatory Breast Cancer Program Dana Farber Cancer Institute Overview Inflammatory
Breast Cancer. Dr. Andres Wiernik 2017
Breast Cancer Dr. Andres Wiernik 2017 Agenda: The Facts! (Epidemiology/Risk Factors) Biological Classification/Phenotypes of Breast Cancer Treatment approach Local Systemic Agenda: The Facts! (Epidemiology/Risk
Circulating tumor cells as biomarker for hormonal treatment in breast and prostate cancer. Michal Mego
National Cancer Institute, Slovakia Translational Research Unit Circulating tumor cells as biomarker for hormonal treatment in breast and prostate cancer Michal Mego 2 nd Department of Oncology, Faculty
Metastatic breast cancer: sequence of therapies
Metastatic breast cancer: sequence of therapies Clinical Case Discussion Nadia Harbeck, MD PhD Breast Center, Department of Gynecology and Obstetrics University of Munich, Ludwig-Maximilians University
Adjuvant endocrine therapy (essentials in ER positive early breast cancer)
Adjuvant endocrine therapy (essentials in ER positive early breast cancer) Giuseppe Curigliano MD, PhD Breast Cancer Program Division of Experimental Therapeutics Outline Picking optimal adjuvant endocrine