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FIRST EDITION DECEMBER 2009

A ROADMAP FOR RESEARCH


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Canadian Institutes of Health Research

Health Canada

Public Health Agency of Canada

Canadian Breast Cancer Research Alliance, 2009

Published December 2009

ISBN 978-0-9864969-0-5

This document is available at www.nationalframework.ca

Contact:

[email protected]

416-596-6598


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TABLE OF CONTENTSForeword rom Co-Chairs 5

Listing o Working Groups 5Part One: National Summit Working Group Members 5Part Two: National Framework Working Group Members 6

1. Executive Summary 7

2. Summary 9Research Themes 11Research Priorities 12

3. Rationale or the National Framework 17Setting the Stage 17Dening the National Framework 17Stakeholder Expectations 18Outline o this Document 18

4. Setting the Context 19

Overview 19

Impact on Canadians 19Funding o Breast Cancer Research 20Strengths and Limitations o the Current Breast Cancer Research System 22

5. Approach and Methodology 23Overview 23Methodology 24Part One: Preparation or the National Summit 24Part Two: Establishing Priorities Following the National Summit 31

6. Identiying the Research Priorities 33

Overview 33Foundational Elements o the Breast Cancer Research System in Canada 33Research Priorities by CSO Category 33

CSO Category 1: Biology 34CSO Category 2: Etiology (Causes o cancer) 38CSO Category 3: Prevention 42CSO Category 4: Early Detection, Diagnosis and Prognosis 43CSO Category 5: Treatment 47CSO Category 6: Cancer Control, Survivorship, and Outcomes Research 51CSO Category 7: Scientic Model Systems 56

Prioritized Research Themes 58A. Mechanisms o Cancer Development 58B. Molecular Detection and Prediction 58C. Personalized Medicine 59

D. Cancer Progression and Dissemination 60E. Psychosocial, Survivorship and Health Services 60F. Transerring Knowledge into Practice 61

Research System/Inrastructure Supports 61Discussion 62

continued..


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7. Call to Action 65Overview 65Collaborating or Success 65CBCRAs Commitment 66Turning Strategy into Action 66

Appendices 69Appendix A CBCRA Board o Directors (2007-2009) 69Appendix B Detailed Breakdown o Funding by CSO Code 71

Appendix C Denition o Key Terms 75Figures and TablesFigure 1: Cancer Research Investment by Cancer Site 20Figure 2: Breast Cancer Investment by CSO Category 21Figure 3: Breast Cancer Research Investment by Funding Mechanism and CSO Category 22Figure 4: Process Overview Developing the National Framework 23

Table 1: Summary Statistics or Breast Cancer in Females, Canada - 2009 (estimates) 19Table 2: Summary o Data Gathered rom Key Stakeholders Prior to the National Summit 25Table 3: List o State o the Science Papers May 2008 26Table 4: Summary o Consolidated Findings rom Stakeholder Input Prior to the National Summit, May 2008 27Table 5: Distribution o 2007 Breast Cancer Research Investment by CSO Code 70


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FOREWORD FROM CO-CHAIRS

Canada is at the oreront o international eorts across many areas o breast cancer research. Our expertise andtechnical capabilities are highlighted by an ever-increasing number o signicant discoveries by Canadian cancerresearchers.

From a strategic standpoint, it became clear to many o us in the breast cancer community that to take ull advantageo this countrys outstanding research talent and capabilities, a more co-ordinated national approach to breast cancer

research is required. Without the guidance o a high-level plan there is a risk that research will occur in silos and thatresources will not be used or maximum eectiveness.

The National Breast Cancer Research Framework the rst initiative o its kind or breast cancer research in the world provides such an approach.

The National Framework presented here is the product o a broad-based, comprehensive and collaborative process.It refects the input o unders, breast cancer survivors, researchers and clinicians rom across the country and, lookingahead, oers a coherent vision o the most promising areas or breast cancer research. We encourage stakeholders tobecome amiliar with the research priorities identied within the National Framework, and unders to collaborate onunding decisions based on those priorities.

As co-chairs and active researchers, we have ull condence in the process used or developing the National Framework.

We are also enthusiastic about the direction it sets or breast cancer research in this country and have high expectationsor the positive outcomes resulting rom more ocused research activity.

We urge Canadas breast cancer research community to ully support the National Framework and its recommendations.By harnessing our strengths and working more eectively together, we can maximize the benets o Canadian breastcancer research.

Eva Gruneld MSc, MD, DPhil, CCFPCo-Chair, National Framework Working GroupDirector, Knowledge Translation ResearchHealth Services Research ProgramCancer Care Ontarioand the Ontario Institute or Cancer ResearchToronto, Ontario

Morag Park PhD, FRSCCo-Chair, National Framework Working GroupScientic DirectorCIHR Institute o Cancer ResearchMember, CBCRA Board o DirectorsMontreal, Quebec

LISTING OF WORKING GROUPSThe contribution o the ollowing individuals to the development o this report is acknowledged with gratitude:

Part One: National Summit Working Group Members

Dr. Phil Branton (Co-Chair), CIHRDr. Moira Stilwell (Co-Chair), CBCFDr. Elizabeth Eisenhauer, NCIC/CCSDiana Ermel, CBCNHeidi Liepold, PHAC

Dr. Ivo Olivotto, CBCRA Research AdvisoryCommittee ChairDr. Morag Park, ResearcherDr. Cathy Popadiuk, CBCRA Board Member-at-Large


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Sta SupportNicola Lewis, CBCRA Executive DirectorDr. Pascale Macgregor, CBCRA Research Program DirectorDr. Jane Cooke-Lauder, Bataleur Enterprises Inc. (consultant)

Part Two: National Framework Working Group Members

Dr. Eva Gruneld (Co-Chair)Director, Knowledge Translation ResearchHealth Services Research ProgramCancer Care Ontario and the Ontario Institute orCancer ResearchHealth services, survivorship

Dr. Morag Park (Co-Chair)Scientic Director, CIHR Institute o Cancer ResearchMember, CBCRA Board o DirectorsMolecular biology o cancer

Dr. Heather BryantVice-President, Cancer Control, Canadian PartnershipAgainst CancerCancer epidemiology and prevention

Dr. Mario ChevrettePresident, The Cancer Research SocietyMolecular biology o cancer

Dr. Elizabeth EisenhauerCo-Chair, Canadian Cancer Research AllianceChair, Canadian Partnership Against Cancer ResearchAction GroupMember, CBCRA Board o DirectorsClinical trials

Dr. Margaret FitchHead, Oncology Nursing, Sunnybrook Research InstituteOncology nursing and supportive care

Dr. Christine FriedenreichResearch Scientist, Division o PopulationHealth and InormationTom Baker Cancer CentreCancer etiology and prevention

Dr. Karen GelmonHead Investigational Drug Program, Advanced TherapeuticsDept. o Medical Oncology, BC Cancer AgencyClinical trials, drug development

Dr. Thomas HackAssociate Proessor, Faculties o Medicine, Nursing, andGraduate Studies, University o ManitobaClinical Psychologist, CancerCare ManitobaMember, CBCRA Research Advisory CommitteePsychosocial interventions or cancer patients

Dr. Claire HollowayAssociate Scientist and Surgical OncologistSunnybrook Health Sciences CentreChair, CBCRA Research Advisory CommitteeClinician/Surgeon, Image-guided surgery, Translationalresearch, Population based studies

Dr. Tom HudsonPresident and Scientic DirectorOntario Institute or Cancer ResearchCancer genetics and genomics

Dr. Victor Ling

Scientic Director, Terry Fox Research InstituteCancer biology

Dr. Sylvie MaderProessor, Institute or Research in Immunology andCancer, University o MontrealMember, CBCRA Research Advisory CommitteeEndocrinology, cellular and molecular biology o cancer

Dr. Michael PollakDirector, Cancer Prevention Centre, Segal Cancer CentreProessor, Department o Oncology, McGill UniversityCancer therapy and cancer prevention strategies

Dr. Jim WoodgettDirector o Research, Samuel Luneneld Research InstituteMount Sinai HospitalMember, CBCRA Research Advisory CommitteeMolecular biology o cancer

Dr. Martin YaeSenior Scientist, Sunnybrook Health Sciences CentreMember, CBCRA Research Advisory CommitteeEarly detection, digital mammography

Chapter 1: Executive Summary


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1. EXECUTIVE SUMMARYBreast cancer is the most requently diagnosed type o cancer among Canadian women. Over the last two decades,it has received an increasing amount o attention leading to vast improvements in screening and treatment. However,emale breast cancer rates in Canada remain among the highest in the world1 leading to a consensus view that moreresearch is required to successully prevent and manage this complex disease.

Investment in breast cancer research has supported the development o considerable Canadian research talent andcapabilities and has ostered many breakthrough discoveries. However, to maximize Canadas contribution to breast

cancer research, now and in the uture, there is a need or more eective use o resources, increased collaboration andagreement on a set o national research priorities.

To address this need, the Canadian Breast Cancer Research Alliance (CBCRA) established a broad-based consultationprocess to develop a strategic ramework or the unding o breast cancer research in Canada.

The resulting National Framework or Breast Cancer Research (National Framework) is a Roadmap or Research. Itidenties existing and emerging research priorities, encourages collaboration among unders and articulates a call toaction aimed at all members o the Canadian breast cancer community.

The National Framework represents a new paradigm

in research prioritizationAlthough national plans currently exist or cancer, diabetes, and heart disease, the National Framework is unique in itsocus on research and its call or collaboration among unders. Most signicantly, this National Framework:

Denes strategic research priorities, covers all aspects o the breast cancer research system and includes areas1.that could be relevant to other cancer sites;

Establishes a streamlined approach or achieving and measuring high levels o scientic rigour and research2.impact;

Is orward looking and acknowledges the importance o both short-term and longer-term initiatives.3.

The National Framework identies areas or high-impact researchResearch priorities were selected through a rigorous, consultative process to ensure agreement that each o theseresearch advances would benet Canadians and improve Canadas global competitiveness in cancer research. Suggestedareas or investment are presented in two linked ways: as broader overarching themes and as more ocused individualresearch priorities.

Six overarching research themes were identied:

Mechanisms o Cancer DevelopmentA.

Molecular Detection and PredictionB.

Personalized MedicineC.

Cancer Progression and DisseminationD.

Psychosocial, Survivorship and Health ServicesE.

Transerring Knowledge into Practice.F.

1 Canadian Cancer Societys Steering Committee: Canadian Cancer Statistics 2009. Toronto: Canadian CancerSociety, 2009.www.cancer.ca/statistics.

http://www.cancer.ca/statisticshttp://www.cancer.ca/statistics


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In addition, 17 high-impact research priorities were identied, mapping to the Common Scientic Outline, an organizingramework used by most national and international research granting agencies:

CSO Category Research Priority

Biology

GENETICS The genetic and epigenetic basis o breast cancer development1.

INITIATION Deciphering the molecular pathways implicated in breast cancer initiation2.

METASTASIS Understanding the cause o metastatic breast cancer and identiying new3. avenues or interventions

Etiology

BREAST CANCER RISK The infuence o liestyle and environmental actors on the risk o4.developing breast cancer

BREAST CANCER CAUSES I The genetics and hormonal causes o breast cancer5.

BREAST CANCER CAUSES II Understanding the interplay o multicausal actors: genetics6.and environment

PreventionPREVENTION (INTERVENTIONS) Interventions to study the infuence o liestyle and7.environmental actors on the risk o developing breast cancer

Early Detection,Diagnosis andPrognosis

DETECTION Better approaches to early detection and diagnosis8.

BIOMARKERS I Development and evaluation o new biomarkers (including biomarkers or9.diagnosis) and the optimization o treatments or individual patients

BIOMARKERS II Clinical setting/clinical trials to assess clinical sensitivity and specicity o10.new biomarkers

TreatmentNEW TREATMENTS Discovery and development o new treatments or breast cancer11.

CLINICAL TRIALS Clinical trials o new promising therapies12.

Cancer Control,Survivorship,and OutcomesResearch

SURVIVORSHIP AND QUALITY OF LIFE INTERVENTIONS Psychosocial and survivorship13.interventions

HEALTH-CARE ISSUES Analysis o the nancial and health-care delivery issues acing breast14.

cancer patients across the cancer continuum

KNOWLEDGE TRANSLATION AND BEST PRACTICES Interventions to improve knowledge15.translation and disseminate best practices in breast cancer across the cancer continuum

LINK WITH CLINICAL DATA Developing mechanisms to link clinical trial data with16.administrative health databases or studies on long-term outcomes and late eects

Scientic ModelSystems

ANIMAL MODELS Developing new animal and cellular models to study response to17.therapeutics and mimic human breast cancer development

The National Framework requires a realignment o existing andsome new unding

In 2007, at least $46.8M was spent on breast cancer research in Canada, most o the investment being made in the ormo investigator-initiated operating grants, also known as discovery research. Although this type o unding mechanism hashistorically received the major share o research unding, there appears to be a general trend toward increased supportor more targeted research.

In assessing the unding needs or the National Frameworks 17 research priorities, a continuation o balanced support



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or ongoing research initiatives is endorsed. However, new thinking about research investment is also encouraged, giventhat a third o the identied research priorities are not currently unded in Canada.

Successul implementation o all aspects o the National Framework will require additional unding or breast cancerresearch as well as some additional investment in inrastructure and capacity development across Canadas researchsystem.

The National Framework includes a Call to Action

All members o the breast cancer research community are invited to become amiliar with the National Framework1.document and to work together to achieve the ultimate outcome: a world where no person need ear breast cancer.

Breast cancer research unders across Canada are asked to adopt a set o guiding principles2. 2 and to mobilize supportor both oundational research and the identied priorities.

Policy and practice infuencers are asked to apply existing research ndings to policy and practice as they relate to3.breast cancer, cancer and chronic disease, and to engage with researchers and academics to shape uture studiesaligned with policy development.

Industry (e.g., pharmaceutical companies, biotechnology companies, sotware developers, equipment manuacturers4.is encouraged to participate in new collaborative opportunities.

Provincial and hospital oundations are asked to allocate 10 per cent o their unds to these national priorities.5.Donors are encouraged to amiliarize themselves with the National Framework and to request that the organizations6.receiving their support embrace these priorities and recommendations.

CBCRA is committed to leading the implementation o the National Framework, and to ensuring it is monitored, updatedand evaluated. As part o this commitment, CBCRA will also acilitate the development o a network o unders alignedwith the National Framework, ostering new collaborations aimed at ensuring the most eective use o resources.

2. SUMMARY

A National Framework or Breast Cancer Researchis needed in Canada at this time

One o every nine Canadian women is expected to develop breast cancer during her lietime and one in 28 will dieo the disease. In every adult age group, breast cancer is the most common emale cancer.3 This is in contrast to menor whom breast cancer remains rare. While incidence and mortality rates have continued to decline, many Canadiansare concerned because emale breast cancer rates in Canada remain among the highest in the world.4 Many importantquestions remain unresolved.

The good news is that over the past teen years, investment in breast cancer research has seen a twenty-old increase.

This has led to the development o signicant research talent and contributed to breakthrough discoveries. Theopportunity exists to maximize Canadas contribution to tackling breast cancer globally by leveraging and co-ordinatingcurrent, leading edge, internationally recognized projects. However, to achieve this level o global impact, unders willneed to collaborate more eectively in setting priorities, deploying resources and promoting their strengths.

2 For a listing o these principles see Discussion section in Chapter 6 Identiying the Research Priorities: pg 62.3 Canadian Cancer Statistics 2009 by the Canadian Cancer Society, Statistics Canada, Provincial/Territorial Cancer Registries and the

Public Health Agency o Canada. Available at www.cancer.ca.4 Ibid.

Chapter 2: Summary
http://www.breast.cancer.ca/http://www.breast.cancer.ca/


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Members o the Canadian Breast Cancer Research Alliance5 (Avon Foundation or Women Canada, Canadian BreastCancer Foundation, Canadian Breast Cancer Network, Canadian Cancer Society, Canadian Institutes o Health Research,Health Canada and the Public Health Agency o Canada) determined the need to capitalize on the growth o Canadianresearch talent, the widening interest in strategic research investment and the burgeoning knowledge about breastcancer to undertake an inclusive process to develop a national breast cancer research strategic ramework that wouldguide all unders o breast cancer research in Canada.

Extensive discussions involving unders, breast cancer patients and survivors, and researchers rom across Canada andinternationally, led to the development o the National Framework presented in this document.6

The opportunity is clear: to identiy existing and emerging research priorities, areas that maximize Canadas comparativeadvantages and represent the best t o Canadian initiatives within a larger set o provincial/territorial, regional, nationaland international initiatives, and to articulate a call to action. The National Framework builds on oundational elementsalready in place. The goal is to harness the existing momentum to increase levels o research impact while usingresources more eectively. By articulating what is most important, the National Framework challenges the breast cancercommunity to step orward and act on these agreed priorities.

CBCRA has acilitated the development o the National Framework,but shares responsibility with other unders to implement it

Championing the process was a natural evolution or the Alliance. Moving orward, CBCRA is committed to the

successul adoption and implementation o the National Framework by the under community. CBCRA will be updatingand reporting on the priorities on a regular basis.7

The National Framework represents a new paradigm inresearch prioritization

The concept o a National Framework builds on the development o national disease state plans such as those or cancerheart and diabetes. However, it is novel in its exclusive ocus on research and collaboration among unders.

Features dening this new paradigm include:

It is strategic in terms o dening priorities and putting in place an updating and monitoring process.1. 8 However,it is not a strategic plan in the sense that it does not prescribe requirements or any one organization.

It provides a balanced portolio o options, covering all aspects and elements o the breast cancer research2.system. Further, some o the priorities identied within the National Framework related to early pillar researchsuch as genomics and gene-related studies will likely provide insights that will be relevant to other cancer sites.

It establishes the groundwork or achieving and measuring high levels o scientic rigour and research impact in3.a streamlined manner.

It is orward looking, acknowledging the importance o short-term as well as longer-term initiatives. The National4.Framework identies dierent issues and dierent approaches to research, recognizing that they will result inactionable ndings over dierent time periods and that all are important or a robust research system.

5 Brie overview o the Alliance is provided in Chapter 3: Rationale or the National Framework: pg 17.6 For more detail see Chapter 5 Approach and Methodology: pg 23.7 For more detail see Chapter 7 Call to Action: pg 65.8 Ibid.

Chapter 2: Summary


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The National Framework identies areas or high-impact research

The National Framework identies the continuing need or such oundational elements as investigator-initiated researchacross the continuum, clinical trials inrastructure and activity and platorms or innovation such as molecular imaging.9

In addition, it selects a small number o overarching and cross-cutting themes as well as a longer set o rened researchpriorities, spanning the cancer continuum. These have been chosen through a rigorous, scientic and inclusive process.The objective is that, i unded, any o these research areas will benet Canadians and improve Canadas globalcompetitiveness.

The six research themes are:

MECHANISMS OF CANCERA.DEVELOPMENT

Includes research on cellular, biological, liestyle actors; e.g., obesity or otherrisk actors and their infuence on the risk o developing breast cancer. A betterunderstanding o the genetic deects responsible or cancer developmentand o the mechanisms by which external actors promote genetic alterationscould lead to prevention strategies.

MOLECULAR DETECTION ANDB.PREDICTION

Includes research on early detection o breast cancer, including non-mammography-based tools, and research into more eective ways todistinguish between what is breast cancer and what is not, in order toreduce overdiagnosis. It will also look at linking 3-D imaging to disease andmicroenvironment.

PERSONALIZED MEDICINEC.Includes research on systemic approach to biomarker validation and genetargets, genomic screens, companion studies with treatment links to identiybiomarkers predictive o response to treatment, treatment o recurrent breastcancer and decision-making tools or treatment o primary disease.

CANCER PROGRESSION ANDD.DISSEMINATION

Includes research on markers and predictors o breast cancer progression/metastasis, understanding how to block metastatic pathways, theidentication o which lesions will progress to invasive cancer and onprediction and prevention o breast cancer recurrence.

PSYCHOSOCIAL, SURVIVORSHIPE.AND HEALTH SERVICES

Includes research on the psychosocial aspects o breast cancer, such asinterventions to improve quality o lie o breast cancer patients throughoutthe course o the disease, and health-care delivery to breast cancer

patients. This area includes biomedical and clinical approaches to access,survivorship and quality o lie issues (e.g., late eects).

TRANSFERRING KNOWLEDGEF.INTO PRACTICE

This cross-cutting theme refects the intent o the national rameworkto ensure that research makes a dierence: that evidence is movedinto practice to the benet o all Canadians. This theme establishes theexpectation that in all the work that is undertaken as part o the NationalFramework, ways are sought to ensure that the best questions areormulated and unded, that what is known inorms the development ourther studies and that when a body o knowledge emerges, it is used toinorm, and possibly change, current practice and policy.

9 For more detail see Chapter 6 Identiying the Research Priorities: pg 33.

Chapter 2: Summary


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At a more detailed level, 17 high impact research priorities across the Common Scientic Outline, an organizingramework used by the majority o research granting agencies, were identied as outlined below:10

CSOCategory

Research Priority11 Description

Biology

GENETICS The1.genetic and epigeneticbasis o breast cancer

development

Cancer is a disease o the genes. This research priority will ocus onidentiying the gene-altering changes underlying cancer initiation andprogression. A better understanding o the role played by genetic andepigenetic changes implicated in breast cancer and the discovery o

new breast cancer susceptibility genes could lead to better strategies orcancer prevention and treatment.

INITIATION 2.Deciphering themolecular pathwaysimplicated in breastcancer initiation

Cancer initiation is thought to result rom alterations to the molecularmachinery regulating the normal unctioning o cells. This researchpriority will study these alterations and the actors infuencing them,and the consequences o these alterations on breast cancer initiation.The results o this research could be highly clinically relevant throughthe identication o molecular pathways that could be targeted by newtherapeutic interventions to block cancer initiation.

METASTASIS 3.Understanding thecause o metastatic

breast cancerand identiyingnew avenues orinterventions

Metastatic breast cancer results in mortality rom the disease and is stillpoorly understood. Thereore, gaining a better understanding o the

process o invasion o cancer cells throughout the body is critical andshould result in the development o new strategies or treatment ometastatic breast cancer.

Etiology

BREAST CANCER4.RISK The infuenceo liestyle andenvironmentalactors on the risk odeveloping breastcancer

Research in this priority area will attempt to identiy modiable risk actorsimplicated in the development o breast cancer. This could lead to thedevelopment o new prevention strategies and interventions.

BREAST CANCER5. CAUSES I Thegenetics and hormonalcauses o breast cancer

Certain genes or hormonal actors have been linked to the development

o breast cancer in some groups o individuals. This research priorityexplores this link in more detail, and could lead to the development onew interventions or treatments to reduce the risk o breast cancer incertain populations.

BREAST CANCER6.CAUSES II Understanding theinterplay o multicausalactors: genetics andenvironment

The interaction o genes with liestyle actors (gene-environmentinteraction) could play an important role in breast cancer risk. Researchin this priority area will study the interaction o dierent actors, such asgenetic predisposition or exposure to a certain environment on the risko developing breast cancer. The results o this research could have animportant impact in the development o new breast cancer preventioninterventions.

Prevention

PREVENTION7.

(INTERVENTIONS) Interventions to studythe infuence o liestyleand environmentalactors on the risk odeveloping breastcancer

Specic actors continue to be identied as infuencing the risko developing breast cancer, particularly in some subpopulations.Research in this priority area will aim to develop new population-basedinterventions that could be introduced to reduce breast cancer incidence.

10 For more detail on the Common Scientic Outline and priority setting process see Chapter 3 Approach and Methodology: pg 17.

Chapter 2: Summary

11 Additional inormation on each o these Priorities is included in Chapter 6 Identiying the Research Priorities (pg 33) under the ollowingheadings: Current Funding Levels; Current Research Activity; Possible Research Questions; Proposed Investment Requirements;Readiness to Initiate Research, Timing o Impact, Uniqueness to Breast Cancer and System Support Requirements.


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CSOCategory


EarlyDetection,DiagnosisandPrognosis

DETECTION Better8.approaches toearly detection and

diagnosis

This research priority will ocus on the development o new approachesto breast cancer screening and on the discovery o new tools leadingto more accurate diagnoses and to more personalized treatment o the

disease.BIOMARKERS I 9.Developmentand evaluation onew biomarkers(including biomarkersor diagnosis) andthe optimizationo treatments orindividual patients

Research in this priority will lead to the discovery and validation o newbiomarkers. New diagnostic biomarkers will provide critical inormation ormore accurate disease characterization. Predictive biomarkers will orecastpatient response to therapy and could lead to the development o newtreatment targets.

BIOMARKERS II 10.Clinical setting/

clinical trials to assessclinical sensitivity andspecicity o newbiomarkers

Following the discovery o new biomarkers, clinical trials will be requiredto assess their use in a clinical setting, particularly or some specic

subtypes o breast cancer. The results o these trials will have an importantimpact on the development o new personalized therapeutic strategiesby providing predictive inormation on response to therapy or specicgroups o breast cancer patients.

Treatment

NEW TREATMENTS 11.Discovery anddevelopment o newtreatments or breastcancer

More specic and eective therapies are required or breast cancerpatients. This research priority area will ocus on the development obetter treatments, particularly or some specic subtypes o breast cancer.

CLINICAL TRIALS 12.Clinical trials o newpromising therapies

Following the discovery o new promising therapies, clinical trials andrelated companion studies test these new agents on breast cancerpatients. Clinical testing and applications o new breast cancer therapiesand the assessment o side eects, toxicity and pharmacodynamics is acritical step in the implementation o these therapies.

CancerControl,Survivorship,andOutcomesResearch

13. SURVIVORSHIP ANDQUALITY OF LIFEINTERVENTIONS Psychosocialand survivorshipinterventions

Research in cancer survivorship covers the range o research domains rombasic biomedical (e.g., to understand the underlying mechanisms leadingto late eects o treatment modalities); clinical (e.g., to test interventionsto ameliorate late eects; health service interventions to improve thequality o survivorship care; randomized trials to improve the evidentiarybasis or elements o ollow-up care during survivorship); and populationstudies (e.g., to understand the impact o public health interventions toimprove liestyle actors on the outcomes or cancer survivors).

Research in quality o lie could lead to the development o new

interventions or improving the quality o lie o breast cancer patientsacross the course o the disease, and promoting psychological adjustmentto the diagnosis o breast cancer and to treatment eects.

Chapter 2: Summary

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CSOCategory


CancerControl,Survivorship,and

OutcomesResearch(contd)

14. HEALTH-CARE ISSUES Analysis o the nancialand health-care

delivery issues acingbreast cancer patientsacross the cancercontinuum

This area o research examines quality o care, access to care (includingtimeliness and equity), and actors associated with variations in qualityand access. Studies examine the health system requirements to provideoptimum quality o care throughout the cancer continuum (rom healthsystem requirements to improved screening, reduced wait times ordiagnosis, and improved end-o-lie care). This research also studiespatients preerences and needs through the cancer continuum.

In addition, individuals aected by breast cancer and their amily/caregiversace economic challenges. Research in this area could ocus on the nancialimplications o a breast cancer diagnosis; it could include an evaluation o thelong-term economic and employment implications or breast cancer patientsand their amilies. The results o this research could have an important impacton the development o new health services and care delivery policies.

15. KNOWLEDGETRANSLATION (KT)AND BEST PRACTICES Interventions toimprove knowledgetranslation anddisseminate bestpractices in breastcancer across thecancer continuum

New initiatives in this area will aim to improve the application o researchndings into policy and practice and identiy which KT interventionsare most eective or breast cancer. An understanding o the barriers toand supports or the successul application o research results to breastcancer is needed. Research will also identiy the most eective strategies

to implement best practices in breast cancer care. This could include thedevelopment o new communication approaches, tools and methods toacilitate, or example, communicating therapeutic options to patients.This research could also have an important impact on breast cancerpatients through signicant improvement in the translation o researchndings into new policies.

16. LINK WITH CLINICALDATA Developingmechanisms to linkclinical trial datawith administrative

health databases orstudies on long-termoutcomes and lateeects

Linking data collected during clinical trials with administrative healthdatabases enables long-term studies on survivorship and quality olie issues related to breast cancer treatment. This orm o linkage ispotentially powerul because data rom clinical trials (where patients havebeen randomly assigned to treatments and where the precise treatmentregimens are known) may be linked with administrative health databasesproviding inormation about long-term outcomes. For example, a clinicaltrial conducted in 1990, i linked with administrative health databasesrunning to 2005, could provide 15-year, patient-specic inormation onoutcomes compared to population controls. Research in this area willprovide critical inormation or the development o uture therapeuticstrategies and better understanding o late eects o treatments.

ScienticModelSystems

17. ANIMAL MODELS Developing new animaland cellular modelsto study response totherapeutics and mimichuman breast cancerdevelopment

New animal and cellular models are required to study specic subtypeso breast cancer and their response to treatment as well as breast cancerdevelopment and invasion.

Chapter 2: Summary


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Policy and practice infuencers are asked to apply existing research ndings to policy and practice as they relate to3.breast cancer, cancer and chronic disease, and to engage with researchers and academics to shape uture studiesaligned with policy development.

Industry (e.g., pharmaceutical companies, biotechnology companies, sotware developers, equipment4.manuacturers) is encouraged to participate in new collaborative opportunities.

Provincial and hospital oundations are asked to allocate 10 per cent o their unds to these national priorities.5.

Donors are encouraged to amiliarize themselves with the National Framework and to request that the6.organizations receiving their support embrace these priorities and recommendations.

CBCRA has committed to playing a leading role in supporting the implementation o the National Framework, as wellas to its ongoing monitoring, evaluation and updating. To that end, CBCRA will itsel adopt two priority themes orimplementation as part o Phase IV o the Alliance (2010-2015). In addition, CBCRA will support the development o anetwork o unders wanting to embrace the recommendations o the National Framework and to work together in newways to prevent and/or mitigate the eects o breast cancer, reduce recurrence and, when not curable, transorm breastcancer rom a killer into a chronic disease.

Chapter 2: Summary


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3. RATIONALE FOR THE NATIONAL FRAMEWORK

Setting the Stage

Breast cancer currently commands the highest level o research unding among all cancer sites, and much leading edgeand internationally recognized research is underway across the country. However, emale breast cancer rates in Canadaremain among the highest in the world.18 Donors are demanding higher levels o accountability and more co-operationamong unders and researchers locally, nationally and globally. New and dierent ways o working together are required.

Against this backdrop, the CBCRA Board o Directors,19 prior to entering a new phase o the partnership, embarkedupon a strategic review. The Alliance, a cross-sectoral partnership representing public, private, non-prot and breastcancer survivor organizations,20 is committed to nding ways to prevent breast cancer, improve survival rates and thelives o those aected by the disease. Since its inception in 1993, as a recognized leader in breast cancer research inCanada, CBCRA has awarded more than $197M to 583 breast cancer research initiatives covering a broad range otopic areas. However, CBCRAs most recent external expert review panel (Sutclie et al, 2007), 21 while applauding thesuccess achieved by the Alliance, also challenged it to become more strategic and proactive in shaping the breast cancerresearch landscape.

In September 2007, the Board took action on these review ndings and initiated the development o a nationalramework or breast cancer research. A working group22 was ormed, chaired by Drs. Phil Branton (Scientic Director,CIHR Institute o Cancer Research at the time) and Moira Stilwell (member, National Board o Directors, Canadian BreastCancer Foundation at the time and medical oncologist), and charged with the planning and hosting o a National Breast

Cancer Research Summit as the rst major milestone in the development o this National Framework.

Dening the National Framework

The National Framework is:

A roadmap to guide the eorts o all members o the breast cancer community in moving breast cancer research1.orward: generating new knowledge and encouraging urther exploration by building on ndings and adoptingnew knowledge into policy and practice settings.

Inclusive in that it recognizes and leverages the oundational elements o the breast cancer research system2.that are already in place (such as capacity, inrastructure, partnerships, state o the science globally).

Strategic in that it identies existing and emerging research priorities, areas that build on Canadas comparative3.advantage while representing the best t o Canadian initiatives within a larger set o provincial/territorial,regional, national and international initiatives.

A call to action.4.

It is NOT a traditional strategic plan with goals, objectives and timelines or a specic organization or sector. However,it is similar to a strategic plan in that its adoption and implementation will be monitored and it will remain dynamic:continuing to shape and be shaped by ongoing discoveries and new knowledge in all aspects o breast cancer research.

Chapter 3: Rationale or the National Framework

18

Canadian Cancer Societys Steering Committee: Canadian Cancer Statistics 2009. Toronto: Canadian Cancer Society, 2009.www.cancer.ca/statistics

19 Membership included in Appendix A.20 The Alliance is unded by both Members and Friends. Current Members include: Avon Foundation or Women Canada, Canadian

Breast Cancer Foundation, Canadian Breast Cancer Network, Canadian Cancer Society, Canadian Institutes o Health Research, HealthCanada and the Public Health Agency o Canada. Current Friends o CBCRA include: Breast Cancer Society o Canada, The CancerResearch Society, CURE Foundation.

21 Membership o the External Expert Review Team: Dr. Simon Sutclie, Chair (Vancouver), Dr. Carole Cass (Calgary), Pro. LesleyFalloweld (Brighton, U.K.), Dr. Tom Kean (Washington), Support Dr. Judy Birdsell.

22 Membership included under Listing o Working Groups: pg 5.


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4. SETTING THE CONTEXT

Overview

Many positive developments in breast cancer research have occurred in the last 10-15 years, such as a twenty-oldexpansion o research support to breast cancer rom a reported $2.4M in 199325 to $47M in 2007 (out o a totalinvestment o $403M dedicated to all cancer research).26 However, despite this increase in investment, emale breastcancer rates in Canada remain among the highest in the world.27 This chapter explores the context within which theNational Framework has been developed, rstly in terms o the eect o breast cancer on Canadians, ollowed by an

explanation o research unding levels and the strengths and limitations o the current breast cancer research system.

Impact on Canadians

In 2009, it is estimated that 22,700 women and 180 men will be diagnosed with breast cancer. An estimated 5,400women and 50 men will die o the disease.28 This is a daunting picture. While incidence and mortality rates havecontinued to decline in all age groups, probably due to the uptake o screening mammography, a drop in usage oHormone Replacement Therapy (HRT) and the adoption o more eective adjuvant therapies, many questions remainunresolved.

In every adult age group, breast cancer is the most common emale cancer, accounting or more than 30% o all newdiagnoses in women aged 20-49 and 50-69. Breast cancer represents 20% o all new cancer diagnoses among olderwomen.29 It is the leading cancer cause o death in young women, and ranks second and third, respectively, in olderages. One Canadian woman out o every nine is expected to develop breast cancer during her lietime. O those whodevelop breast cancer, one in our will die o the disease.

Table 1: Summary Statistics or Breast Cancer in Females, Canada 2009 (estimates)30

Number o New Cases 22,700

Incidence Rates 102 per 100,000

Per cent o All Cancers in Females 27.8%

Incidence Rank in Females 1*

Number o Deaths 5,400

Mortality Rate 22 per 100,000

* Excluding non-melanoma skin cancer

Chapter 4: Setting the Context

25 Health Canada. Report on the National Forum on Breast Cancer. Ottawa: Minister o Supply and Services Canada. CatalogueH39/305/994E, 1994.

26 Canadian Cancer Research Alliance: Cancer Research Investment in Canada, 2007: The Canadian Cancer Research Alliances Survey oGovernment and Voluntary Sector Investment in Cancer Research in 2007. Toronto: CCRA, 2009.

27 Canadian Cancer Societys Steering Committee: Canadian Cancer Statistics 2009. Toronto: Canadian Cancer Society, 2009.www.cancer.ca/statistics.

28 Ibid.29 Ibid.30 Ibid.


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Funding o Breast Cancer Research31

The total amount o research unding allocated to breast cancer is dicult to quantiy as there is no complete databaseavailable. The best available data is ound in the Canadian Cancer Research Alliance report on the governmentand voluntary sector investment or 2007. Submission o data is purely voluntary with the current report containinginormation rom 37 organizations unding cancer research. This number includes the largest contributors such as CIHRand the Canadian Cancer Society. Other investments, such as those rom hospital oundations or smaller voluntaryorganizations, are not captured.32 Data is also not available on research being conducted or other diseases that mightrelate to breast cancer. This inormation could be o particular relevance in areas such as liestyle actors infuencing

prevention and survivorship, where commonalities exist. Also, in the longer term, with the higher number o breastcancer survivors, there will be an increasing need to manage co-morbidities.

The CCRA report states that an estimated $403M was invested in cancer research in 2007. More than hal (51%) o this amountis invested in non-site-specic cancer. O the remaining 49%, breast cancer accounts or the greatest share o the site-specicinvestment at 14% ($54.6M).33 Trends over the last our years suggest that breast cancer research unding has increased at a asterrate than or other cancer-specic sites. The ollowing chart depicts research investment across non site-specic and site-specic cancers

Figure 1: Cancer Research Investment by Cancer Site

NON-SPECIFIC/ALL SITES $205.2M

BREAST $54.6M

OTHER SITES $59.2M

PROSTATE $17.2M

LUNG $13.8M

LEUKEMIA $23.7M

BRAIN $15.1M

COLORECTAL $13.6M

TOTAL INVESTMENT - $402,448,190 FROM 2007 CCRA DATA


31 Data or this section has been provided by CCRAs most recent survey o Government and Voluntary Sector Investment in CancerResearch (2007). CCRA has adopted the Common Scientic Outline (CSO) to organize and report on the data. Canadian Cancer ResearchAlliance: Cancer Research Investment in Canada, 2007: The Canadian Cancer Research Alliances Survey o Government and VoluntarySector Investment in Cancer Research in 2007. Toronto: CCRA, 2009.

32 The amount o this unding is not available but is thought to be signicant: or example, in 2007, provincial cancer and hospitaloundations received some $42.7M rom the Weekend to End Breast Cancer.

33 This total investment gure includes all reported projects with breast cancer weightings in excess o 1% which is the CCRA standard. Else-where in this report, a total gure o $47M is used. This gure refects the CBCRA standard o including only breast cancer research projectwith a weighting o more than 50%.


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Across the dierent sectors, the ederal government contributes the greatest amount to breast cancer research approximately 41% ollowed by the voluntary sector, which unds more than a quarter o all breast cancer research inCanada. Multiunded initiatives, including research unded by CBCRA, account or a urther 20%.

The overall pattern o breast cancer research investment across the research spectrum mirrors the overall pattern orall cancers with the majority o research investment going to biology and treatment. Dierences noted include moreinvestment or breast cancer research in the area o early detection, diagnosis and prognosis, and slightly reducedinvestment in biology and treatment as compared to all cancers.

As with all cancers, the largest investment category is biology ($19M or breast cancer), ollowed by treatment ($9.6M

or breast cancer). Prevention receives the smallest amount o research investment or breast cancer and cancer overall($0.61M or breast cancer). It should be noted that the CSO classication system denes prevention quite narrowly:research that might typically be reerenced as prevention is included in the etiology category. This is obviously a limitingactor when interpreting the distribution o research investment according to this classication system.

In reviewing breast cancer investment in greater detail, the ollowing chart shows the allocation o investment by CSO category.

Figure 2: Breast Cancer Research Investment by CSO Category

A prole o the unding mechanisms to which investment dollars are allocated, as shown in the gure below, reveals thatoperating grants34 are by ar the most common mechanism or breast cancer research, accounting or $38M (81%) o the$47M total investment. For all cancers, the dollar amount spent on operating grants is $210.4M (52% o total).

BIOLOGY $19.1M

TOTAL INVESTMENT - $46,774,937 FROM 2007 CCRA DATA

EARLY DETECTION,DIAGNOSIS &PROGNOSIS $7.2M

ETIOLOGY(causes of cancer)

$4.7M

PREVENTION (interventions) $0.61M

TREATMENT $9.7M

SCIENTIFIC MODEL SYSTEMS $0.51M

CANCER CONTROL,SURVIVORSHIP

& OUTCOMES $4.9M


34 Denitions o the dierent unding mechanisms are included in Appendix C.


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Figure 3: Breast Cancer Research Investment by Funding Mechanism and CSO Category($47M) 2007

Strengths and Limitations o the Current Breast Cancer

Research System35It is generally agreed that or research to be successul, the underlying system needs to provide the necessary resourcesand supports. In the arena o breast cancer research, Canada has a strong oundation on which to build and a history owillingness to collaborate.

Canada is exceptionally strong in the biomedical (particularly cancer genetics and cancer biology), clinical trials andhealth services areas. The letrozole trial is an example o Canadian excellence, where research ndings changedclinical practice almost immediately. Internationally recognized individual research excellence exists across the researchspectrum. From a team or group perspective, the NCIC Clinical Trials Group commands international renown.

The universal health-care system, with population-wide access to health care, combined with Canadas multiculturalismoers distinct system advantages. The population-based cancer registries, with some critical changes, provide the

potential or a rich source o data which can be linked with other administrative health databases.However, two major limitations have been identied; namely, unding/capacity development and the ability to movethe knowledge gained rom research into practice. Concerns with respect to unding and capacity building include theneed or greater equity in unding across the research continuum as well as the unding o multidisciplinary team grants.In addition, there is general acknowledgement that the process o moving new knowledge into policy and practiceis lengthy. This process involves stakeholders beyond the research community, and tends to lack standardization andevaluation.


Operating grants Career awards Trainee awards Related supportgrants

Equipment/infrastructure grants

0

$3,750,000

$11,250,000

$15,000,000

$7,500,000

Scientific model systems

Cancer control, survivorship & outcomes

Treatment

Early detection, diagnosis & prognosis

Prevention (interventions)

Etiology (causes of cancer)

Biology

35 Denition used or research system: The unding mechanisms, partnerships, inrastructure requirements, key processes (such asplanning and surveillance) and human resources to support a world-class research enterprise.


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5. APPROACH AND METHODOLOGY

Overview

A multi-tiered, multi-stakeholder approach was adopted to consult, identiy and dene research priorities and theelements o a National Framework. It was developed in two parts Part One included the data gathering necessary toinorm the National Summit and the input received rom that orum. Part Two included the renement o the researchpriorities based on the views expressed at the Summit, urther data gathering and expert scientic input.

The schematic below depicts the dierent stages in the development o the National Framework, rom therecommendations stemming rom the review o CBCRA by the external expert panel and the support o the CBCRABoard, to the completion o the National Framework document.

Figure 4: Process Overview Developing the National Framework

Chapter 5: Approach and Methodology

PART 1 - PREPARATION PART 2 - ESTABLISHING PRIORITIES

007 2007

2008 2008

2009 2009

2010 2010

CBCRA External Review Report

NationalFrameworkWorking Group

National Breast CancerResearch Summit

Summit proceedings/Post-summit development

National Breast CancerResearch Framework

Summit PlanningWorking Group

CBCRA Board

engagement/new vision

International initiatives Input from Canadian stakeholders State of the science papers

The Common Scientic Outline (CSO) was adopted as the organizing ramework to classiy the stakeholder data and toshape national breast cancer research priorities.36 It was chosen because it is the system currently used by the majority onational and international research granting agencies.

This chapter presents an overview o the process undertaken to develop the National Framework. The proposed researchpriorities are presented in Chapter 6.

36 The Common Scientic Outline is a classication system organized around seven broad areas o scientic interest in cancer research,developed by the International Cancer Research Portolio, a joint initiative o International Cancer Research Partners asdened at www.cancerportolio.org/cso.jsp.

Other national agencies that classiy research by CSO include CCSRI, CBCF, CIHR and members o CCRA. Internationally, such organiza-tions as the Wellcome Trust, Medical Research Council, Cancer Research UK and the Breast Cancer Campaign use the CSO classicationas do the American Cancer Society, Susan G. Komen, the National Cancer Institute and the Department o Deense in the U.S.
http://www.cancerportfolio.org/cso.jsphttp://www.cancerportfolio.org/cso.jsp


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Methodology

The breadth and depth o existing knowledge, inrastructure and resources created the need or an integrated, phasedmethodology, combining use o existing data with new data gathering, analysis and synthesis, and expert opinion. Asalready indicated, two distinct stages in the process occurred, linked by the hosting o a National Summit in May 2008.

In addition to identiying research priorities, inormation was collected about the critical inrastructural and resourcerequirements that enable the pursuit o world-class research. These ndings are provided at the end o this section.

Part One: Preparation or the National Summit

Part One included the data gathering necessary to inorm the National Breast Cancer Research Summit and the inputreceived at this orum.

1a. Pre-Summit Data Gathering

International Initiatives

Context or the Canadian data was provided by a review o the ollowing international priority-setting initiatives in breastcancer research, all o which had been conducted within the preceding 18 months:

Breast Cancer Campaigns breast cancer gap analysis and the identication o translational research priority areas (U.K.); 37

International web-based consultation on priorities or translational breast cancer research (Top Ten Project or theSt. Gallen Research Priorities);38

Caliornia Breast Cancer Research Programs process to identiy research priorities relevant to the role played inbreast cancer by the environment and health disparities;39

U.S. Department o Deense congressionally-directed medical research investment in breast cancer. This is ahighly fexible program, with a vision that is adapted annually and a ocus on addressing research gaps throughinnovative proposals;40

A Collaborative Summit on Breast Cancer Research hosted in Virginia, U.S., by key unding agencies includingthe Avon Foundation, the Breast Cancer Research Foundation and Susan G. Komen or the Cure. This meetingwas attended by approximately 100 invited participants rom across the system, including the private sector.The conerence participants identied several key action items, such as the establishment o a National BreastCancer Planning Committee and a commitment to demonstrating more transparency in sharing inormation andreporting to the public.41

Input rom Canadian stakeholders

As captured in Table 2, data was gathered rom such key Canadian stakeholders as researchers, policy-makers, those whoinfuence policy development, survivors and their amilies/caregivers, and unding organizations:


37http://breast-cancer-research.com/content/10/2/R26.38http://www.toptenresearch.org/#.39http://www.cbcrp.org/sri/40http://cdmrp.army.mil/bcrp/deault.htm41http://www.nih.org/index.php?option=com_content&task=view&id=445&Itemid=551.
http://breast-cancer-research.com/content/10/2/R26http://www.toptenresearch.org/#http://www.cbcrp.org/sri/http://cdmrp.army.mil/bcrp/default.htmhttp://www.fnih.org/index.php?option=com_content&task=view&id=445&Itemid=551http://www.fnih.org/index.php?option=com_content&task=view&id=445&Itemid=551http://cdmrp.army.mil/bcrp/default.htmhttp://www.cbcrp.org/sri/http://www.toptenresearch.org/#http://breast-cancer-research.com/content/10/2/R26


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Table 2: Summary o Data Gathered rom Key Stakeholders Prior to the National Summit

Stakeholder Method Key Findings Comments

Researchers

a) CBCRA:StrategicResearchAgendaWorkshop(SRAW)42

72 participants, representing theull spectrum o breast cancerresearch, including researchers(49), representatives o cancerunding agencies (12), policy-

makers (2) and breast cancersurvivors (9).

Chaired by Drs. William Mullerand Tom Hack; acilitated by Dr.Ivo Olivotto (RAC Chair).

Inormed by State o the Sciencepapers (see below).

Common priorities identied byboth processes include:

Biomarkers; targeted and tailoredtreatmentImproved screening tools andprogramsKnowledge translationRisk reduction/preventionMetastatic breast cancerSurvivorship and psychosocialinterventionsConsideration o marginalized andsubpopulations.

Priorities rom SRAW werepositively received whenpresented inormally tothe Clinical and ScienticAdvisory Board o theCampbell Family Instituteor Breast Cancer Researchin December 2006.

b) NCIC Breast CancerSummit

31 structured key inormantinterviews to identiy themes(breakthroughs, barriers andimmediate opportunities).

Workshop with 22 participants.

PolicyInfuencers43

15 semistructured telephoneinterviews, rom individuals settingor infuencing policy related tobreast cancer at dierent levelsand in dierent jurisdictions acrossCanada. Their involvement inthe policy development processvaried. Overall, good coveragewas attained with respect togeography, subject matter andinterest.

Health human resourcesService modelsScreeningTreatment/curePreventionPalliation.

Policy infuencers saw thevalue o a national breastcancer research strategyin bringing dierent actorstogether to acilitate betterunderstanding across thesystem and better co-ordination o activities.

Survivors,FamilyMembers andCaregivers44

Bilingual web-based surveyinstrument based on existingliterature, expert input, plainlanguage review and rigoroustesting.

Promoted by 11 breast cancer-related organizations.

808 ully completed responses:

Overall, respondents youngerthan norm in the population,

but statistically not signicant.Some small regionaldierences in the data.

Prevention (especially environmentalcauses and risk actors)ScreeningTreatment (especially o metastaticcancer and the wide range oalternative and complementarytreatment approaches).

Need or psychosocial andother supports beore, duringand ater treatment.

Research needed on alternativeand complementary treatmentapproaches.

Appreciation or research doneto date but need or morecollaboration and sharing oinormation among researchers.

Concern about slow progresson many important issues andneed or more ocus.


42 Proceedings rom the CBCRA Strategic Research Agenda Workshop: Inorming CBCRA on Future Strategic Research Priorities (2008- 2013). TorontoDecember 1-2, 2006. Available on the CBCRA website at www.breast.cancer.ca/pd/CBCRA_Strategic_Research_Agenda_Workshop_Proceedings.pd.See also the Advance reading or National Summit Researcher Priorities, Pg 59. Available at www.breast.cancer.ca.

43Data rom telephonic interviews conducted in early 2008 as reported in Policy Infuencers Perspectives on Breast Cancer Research. William E.Maga. May 2008. Available on CBCRA website at www.breast.cancer.ca/pd/Survey_o_Policy_Infuencers.pd.

44Breast Cancer Research Priorities: A survey o survivors and others involved in breast cancer. Brian Rush and Nancy Dubois. May 2008.Available on CBCRA website at www.breast.cancer.ca/pd/Survey_o_Survivors_and_Others.pd.

continued.
http://www.breast.cancer.ca/pdf/CBCRA_Strategic_Research_Agenda_Workshop_Proceedings.pdfhttp://www.breast.cancer.ca/http://www.breast.cancer.ca/pdf/Survey_of_Policy_Influencers.pdfhttp://www.breast.cancer.ca/pdf/Survey_of_Survivors_and_Others.pdfhttp://www.breast.cancer.ca/pdf/Survey_of_Survivors_and_Others.pdfhttp://www.breast.cancer.ca/pdf/Survey_of_Policy_Influencers.pdfhttp://www.breast.cancer.ca/http://www.breast.cancer.ca/pdf/CBCRA_Strategic_Research_Agenda_Workshop_Proceedings.pdf


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Stakeholder Method Key Findings Comments

Funding

Organizations45

Two complementary datagathering approaches:

Web-based survey whichreceived a 35% response rate.13 in-depth key inormantinterviews. Stratied sample

representing national, andprovincial research institutes,cancer agencies and canceroundations.

In general, dierent topicswere covered and where therewas similarity, this was donedeliberately to delve moredeeply into specic issues.

Risk actors and preventionTreatmentDeveloping research capacityLaboratory/basic research.

In rating previously identied 19SRAW priorities, respondents highestpriorities and/or areas o concernincluded:

Genetics-related researchImpact o environmental risk actorsIncreasing the amount o translationresearch. Expanding the ocus ometastasis-related research.

77% o respondentssupportive o developinga national breast cancerresearch strategy.

Funders appeared to wantCanadas breast cancerresearch to be positioned

within a global context; theysaw more megaprojectsenabled through larger andlonger grants; and theyexpected Canadas assets(such as the publicly undedhealth-care system and theculturally diverse population)to be used to better eect inthe uture.

State o the Science Papers

In preparation or the Strategic Research Agenda Workshop, CBCRA Research Advisory Committee members and otherexperts in specic areas o breast cancer research were asked to prepare summary documents describing the State othe Union o breast cancer research in the ollowing areas. These papers were updated or the National Summit andpresented as part o the advance reading materials.

Table 3: List o State o the Science Papers May 200846

Research area Examples o possible research topics Author

Early detectionMammography screeningAlternative methods o detection

Dr. Martin Yae

Epidemiology/Prevention Genetic predispositionRisk actors (modiable and non-modiable)

Dr. Norman Boyd

Health services/Knowledge translation/Policy/Ethics

Evaluation o screening programsKnowledge translation o research results intopolicy and practice

Drs. Lisa Schwartzand Eva Gruneld

Molecular biology and signaltransduction

Biology o breast cancer development andprogression at the cellular and molecular level

Dr. John Hassell

Molecular pathologyPrognostic and predictive indicatorsTumour banks

Dr. David Huntsman

Psychosocial oncologyPsychosocial support and group therapyDecision making and decision aids

Drs. Mary Jane Esplen and Tom Hack

Treatment and clinical trialsNew drugs and vaccinesRadiotherapy and surgical techniques

Dr. Andr Robidoux

Tumour microenvironmentand metastasis

Breast cancer invasionAngiogenesis

Dr. Shoukat Dedhar


45Breast Cancer Research Priorities: A survey o organizations unding breast cancer research in Canada and related key inormantinterviews. Brian Rush and Nancy Dubois. May 2008. Available on CBCRA website at www.breast.cancer.ca/pd/Survey_o_Funders.pd.

46 Papers available as part o the advance reading materials or the National Summit at www.nationalramework.ca.
http://www.breast.cancer.ca/pdf/Survey_of_Funders.pdfhttp://www.nationalframework.ca/http://www.nationalframework.ca/http://www.breast.cancer.ca/pdf/Survey_of_Funders.pdf


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CSOCategory

Prioritized CSO Code Examples o Identifed Research Issues/QuestionsListing o

StakeholdersPrioritizing this Code

4.Earlydetection,diagnosisandprognosis

4.1 Technologydevelopment and/ormarker discovery

4.2 Technology and/or marker evaluation

with respect toundamentalparameters o method

4.3 Technology and/or marker testing in aclinical setting

Biomarkers: identication o the molecular basis/biomarkers o progression, to target therapies orimaging and to understand and predict progressionBreast cancer subtypes: Better appreciation o theunctional meaning o breast cancer subtypes (e.g.,triple negative breast cancer) and implications or

breast cancer progression and or treatment acrosspopulationsLiestyle infuence on breast cancer: How donutrition/liestyle/natural remedies infuence cancerormation, cancer progression and eectiveness otherapy at the molecular level?Better screening tools, including or genetically high-risk womenMolecular imagingAlternative detection methods such as serum-basedmarkers

Researchers: SRAW,NCIC Summit, CBCFBC/Yukon Region 2020:The Future WithoutBreast Cancer Report

Survivors

Funders (Earlydetection a currentpriority with genomicsseen more as anemerging priority)

5.

Treatment

5.1 Localized

therapies: discoveryand development

5.2 Localizedtherapies: clinicalapplications

5.3 Systemic therapies:discovery anddevelopment

5.4 Systemic therapies:clinical applications

Better dening therapy needs or individual patients:

more targeted and better tailored interventionsMicroenvironment o metastatic breastcancer: therapy or metastatic breast cancertargeted at interaction between tumour and itsmicroenvironmentBetter appreciation o the unctional meaning obreast cancer subtypes (e.g., triple negativebreast cancer) and implications or treatment acrosspopulationsPhase I and II intervention trials: ocus on multicentrePhase I and II trials to test novel paradigms orinterventionResearch on the treatments or cancer that spreads

to other parts o the body (metastatic breast cancer)Research on new therapies (such as vaccines andgene therapies) and new surgical and radiationtreatmentsResearch on hormonal therapy (such as tamoxien)

Researchers: SRAW,

NCIC Summit, CBCFBC/Yukon Region 2020:The Future WithoutBreast Cancer Report

Survivors

Funders (Targetedtherapies andGenomics seen asEmerging Priorities)


continued...


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CSOCategory

Prioritized CSO Code Examples o Identifed Research Issues/QuestionsListing o

StakeholdersPrioritizing this Code

6.Cancercontrol,survivorshipandoutcomes

6.1 Patient care andsurvivorship issues

6.4 Cost analyses andhealth-care delivery

6.5 Education andcommunication

Knowledge translation interventions: Knowledgetranser: increase knowledge about interventions,what works, what doesnt, studies o uptake andeectiveness on the interventions where evidenceexistsSurvivorship and Quality o Lie intervention

research: better understanding o issues anddesign o interventionsSupport across the course o the disease,including post-treatment complications (e.g., pain,lymphedema), stress management, mental healthand reintegration issues, body image, sel-esteem,or patients and their amily/caregiversStudying the social infuences on behaviourrelated to breast cancerFinancial issues/aid (e.g., child care; employmentinsurance)Health-care delivery: Need or more co-ordination or communication between playersand in hospitals; more clinical teams and ewerindividual physicians (decreased chances o errors;opportunity or second opinion)Research into plans and policies that will ensurethere are enough trained health-care proessionalsor treatment and supportInequities: inequities and social determinants,equitable access to anticancer drugs across thecountryWhat is the ranking in terms o cost-eectivenesso new technologies relative to the most broadlyused current technologies?

What population-based interventions can be

introduced to increase percentage o womenscreened?The physical and psychological impact o waittimes on patientsWithin an integrated population-based approachto reducing cancer or chronic disease, what nicheactivities related specically to breast cancer arestill required?Eective messaging about personal risk reduction

Researchers: SRAW,NCIC Summit, CBCFBC/Yukon Region 2020:The Future WithoutBreast Cancer Report

SurvivorsPolicy-makers

Funders (TranslationalResearch andEvaluation oSupportive Caredescribed as CurrentPriorities with HealthServices/New Modelsseen more as anEmerging Priority)

7.Scienticmodel

systems

7.1 Development andcharacterization omodel systems

Animal models o breast cancer progressionBreast cancer modelling

Researchers: SRAW



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1b. National Breast Cancer Research Summit (National Summit)

The National Summit was a pan-Canadian, invitational gathering o stakeholders held on May 26-27, 2008 in Toronto.Summit participants included representatives rom cancer care agencies, cancer oundations, non-governmentorganizations with a cancer research mandate, provincial and ederal health research unding organizations, healthresearch agencies and research institutes, as well as researchers, policy-makers, survivors and breast cancer communityleaders at regional and national levels. About 75 o Canadas leading breast cancer research stakeholders, togetherwith prominent international breast cancer representatives gathered with a goal to determine a more strategic andecient path orward. They discussed the current state o breast cancer research, established national research priorities,

identied synergies and agreed on the elements o an optimal pan-Canadian ramework.Priority Setting at the National Summit

A combination o presentations, small group work and plenary sessions allowed participants to discuss issues, challengethe data and present opinions. Presenters described the breast cancer research community as seeking a comprehensiveramework that included not only sustaining important current research but identiying new or improved investment in anumber o priority areas.

The ollowing research priority areas were identied or possible inclusion in the National Framework:

Early diagnosis/Detection: put in place an inexpensive, universal screening tool like a blood test, a ngerprinto high risk. Follow up results, i needed, with a more targeted and expensive test. Importance o imaging

leveraging o the current One Millimetre Cancer Challenge program; research into improving screeningcompliance; enhance understanding o molecular basis o early disease.

Etiology/Prevention/Risk reduction: cancer cannot be prevented without knowing its cause, so ocus on cancergenome: determining this can be used as a prescription or prevention; ocus on the types o breast canceroccurring in young women; learn more about implications o breast density; nd new ways to combat thechallenge o changing behaviours around certain areas; growth actors/estrogen: how can exposure to estrogen/growth actors be reduced and liestyle modulated; include children in the cohort and take advantage o the datagathered by the cohort.

Treatment: personalized medicine reduced toxicity; biological research into metastatic disease; prevention andtreatment o recurrence; understanding o the the role o cancer stem cells; addressing specic issues like triplenegative breast cancer; improving translational science.

Supportive/Palliative/Psychosocial: is this a cancer or breast cancer issue? What is unique to breast cancer and

should be included within the priorities perhaps the ocus on young women?

Health services: access to care and to clinical trials understand the barriers to turning research ndings intoaction; challenge o timely care.

Knowledge translation: how to turn results into change; modelling o barriers to the application o knowledgeinto practice; moving to evidence-inormed practice.

A signicant outcome o the National Summit was armation o CBCRAs leadership role in the continued developmento a national breast cancer research ramework.

Research System Gaps and Challenges

A urther important outcome was the identication o the changes that would be needed to the research system or moreworld-class research to be conducted in Canada.

It is generally agreed that or research to be successul, the underlying system needs to provide the necessary resourcesand supports. Hence the data gathering undertaken by CBCRA also sought to document the systemic changes required inorder or a national ramework to be implemented successully. Researchers at the CBCRA-hosted SRAW workshop wereasked to select what they saw, moving orward, as the key gaps and barriers to the implementation o successul research.These questions were also posed to dierent stakeholder groups to build a broad and consolidated picture. In addition,a ocus group o pre-eminent scientists was convened under the leadership o Drs. Martin Yae and Pascale Macgregorin November 2007.



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At the National Summit, delegates identied the importance o addressing the ollowing system issues in order or theresearch priorities to be implemented successully:48

Introduce closer collaboration across all sectors in the system.

Improve translational science including national standard operating procedures (SOPs), shared testing o

hypotheses at basic and clinical research levels and the rapid clinical validation o new treatments and predictors

o activity through clinical trials.

Improve national inrastructure, including quality collection and banking o tumour tissue, serum and blood; the

integration o electronically linked administrative and research databases; resolving ethical and legal challenges;

and a stronger clinical trials inrastructure (national and international) with a broadening o trials to include

prevention and survivorship.

Improve human resources: developing excellence through unding and recognition approaches.

Introduce innovative unding mechanisms, including creating more fexibility and introducing a single peer

review process.

Develop the political will to make these changes, including better public policy, eliminating provincial boundaries

and strong advocacy or research and participation in clinical trials.

Part Two: Establishing Priorities Following the National Summit

Subsequent to the Summit, the CBCRA Board agreed to continue to lead the work necessary to bring the NationalFramework to ruition, drawing on a new working group o acknowledged experts with the mandate to provide advice onthe renement o research priorities and the development o the overall National Framework.

2a. Creating a National Breast Cancer Research Framework Working Group

The National Framework Working Group (NFWG) was ormed at the end o the summer o 2008, to complete the tasko reaching agreement on the research priorities.49 Dr. Morag Park, a current member o the CBCRA Board, and Dr. EvaGruneld, a past member o the Research Advisory Committee, agreed to act as co-chairs. This 16-person group ohighly respected research leaders was selected based on individual scientic expertise across the cancer continuum andrepresented a range o geographic areas across the country.

2b. The National Framework Working Group in Action

NFWG embarked upon a rigorous and ast-paced seven-step process, building on the existing work, to:

Conrm current and emerging initiatives in breast cancer and cancer at the national and international levels;1.

Dene research themes or priorities and possible research questions by CSO category;2.

Identiy possible unding mechanisms and order o magnitude unding requirements;3.

Establish the nature o the unding required (whether current unding should be sustained, expanded or enabled,4.or new unding initiated);

Determine required research system and inrastructure supports;5.

Assess the priorities according to their uniqueness to breast cancer, the readiness in Canada to undertake the6.research, and the timing o expected impact o the research;

Identiy overarching themes or clustered priorities that span CSO categories.7.


48 A ull listing is available in the Proceedings rom the National Breast Cancer Research Summit. Mapping the Future. Toronto: May 26-27,2008. Available on CBCRA website at www.breast.cancer.ca/pd/summit_app/mt-proceedings.pd.

49 Membership included under Listing o Working Groups: pg 5.
http://www.breast.cancer.ca/pdf/summit_app/mtf-proceedings.pdfhttp://www.breast.cancer.ca/pdf/summit_app/mtf-proceedings.pdf


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Further data gathering was required to inorm the above work. An international scan was conducted to identiy currentand emerging research programs in breast cancer and cancer, primarily in Europe, the U.K., North America and Australia.A national scan to identiy similar Canadian current and emerging research programs was also undertaken. NFWGmembers, amiliar with current and emerging eorts, both nationally and internationally, validated and added to the datato provide comprehensive coverage across the cancer spectrum.

Several separate analyses were also conducted by CCRA using its database, to urther dene breast cancer researchunding by CSO category and code.

NFWG met three times as a group in October and November 2008. Given the complexity and level o detail required,the process also included a series o small group teleconerence calls or one-on-one telephone interviews with workinggroup members. These meetings ocused specically on the research theme(s) relevant to the scientic expertise oeach working group member, allowing or meaningul engagement. This process generated a more in-depth discussionbetween group members, acilitating a careul review o the material and proposed research priorities.50 Consensuson the list o research priorities was achieved and validated at the nal meeting o NFWG, held on January 20, 2009.NFWG then went a step urther with the list o individual priorities, relaxing the CSO ramework to cluster priorities intoresearch themes. Finally, NFWG reviewed the list o research system gaps and challenges generated at the NationalSummit, rening the list to include system gaps relevant to the identied priorities. These system gaps are included inthe descriptions o each research priority in Chapter 6.


50 Between December 3 and 18, 2008, nine small group meetings and ve one-on-one interviews were held with NFWG members andCBCRAs Executive Director and Research Program Director. The majority o NFWG members participated in more than one meetingaddressing several thematic research areas. The results o these in-depth meetings were tabulated or the ourth teleconerencemeeting o NFWG.


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6. IDENTIFYING THE RESEARCH PRIORITIES

Overview

This chapter showcases the work o the National Framework Working Group in nalizing the National Framework,building on the ndings rom Part One, including the proposals developed at the National Summit.

It begins by acknowledging the oundational system elements that need to be maintained i breast cancer research isto thrive in Canada. It goes on to present the research priorities, rst individually and then clustered as priority research

themes. Each research priority is described in terms o a number o elements refecting the criteria used in selecting andassessing them. The chapter concludes with a summary o the required research system changes and a discussion o thepossible unding and other ramications arising rom the National Framework.

Foundational Elements o the Breast Cancer Research System in Canada

Capacity to perorm world-class breast cancer research in Canada has been built up over the years and was given asignicant boost with the ounding o CBCRA in 1993. A broad oundation is now in place that has enabled many criticaldiscoveries.

In discussions around setting priorities or uture research, it was explicitly acknowledged that the oundational elementsneed to continue to ensure the sustainability o uture breast cancer research. Most o these underlying elements are not

exclusive to breast cancer research. However, the challenge rom a unding standpoint lies in trying to determine therelative level to invest in such oundational mechanisms as:

Investigator-initiated grants across the spectrum o breast cancer research; i.e., there is a need or robust open1.competitions beyond the priorities and strategic research identied by unders.

Clinical trials inrastructures including not only cancer treatment centres but national or other groups outside o2.industry.

Platorms or innovation: examples might include biomarker development, molecular imaging and cohort studies.3.

While the total investment in non-industry-unded clinical trials is known, the portion that is breast cancer specic is notavailable at this time. Similarly, while unding levels o operating grants by CCRA survey participants are known, thoserelated to targeted competitions are not tracked. However, a trend toward more targeted research is clearly evident, withthe scientic community expressing a view that the optimal investment ratio between investigator-initiated research andtargeted research is in the range o 70:30.

Research Priorities by CSO CategorySignicant background data supported the selection o each breast cancer research priority (including input romdierent stakeholders gathered beore and during the National Summit; identication and collation o internationallydetermined priorities, current and emerging unded research projects in Canada and internationally). NFWG consideredall o this inormation and through urther rigorous discussion identied the ollowing 17 research priorities. They arepresented below by CSO category and are described in terms o their CSO code,51 the types o research questionsconsidered interesting and important, and the current level o activity together with proposed new unding requirements

and mechanisms.52

Chapter 6: Identiying the Research Priorities

51 A detailed breakdown o current unding by CSO code is provided as Appendix B.52Initiate: New investment is needed to encourage research in this area.

Enable: Some unding is currently directed to research within this CSO code, but additional unding is required.

Sustain: Funding currently in place that needs to be continued.


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CSO Category 1: Biology

1. The genetic and epigenetic basis o breast cancer development(linked to CSO code 1.2)

Cancer is a disease o the genes. This research area will ocus on identiying the gene-altering changes underlyingcancer initiation and progression. A better understanding o the role played by genetic and epigenetic changesimplicated in breast cancer and the discovery o new breast cancer susceptibility genes could lead to better

strategies or cancer prevention and treatment.

Current Funding Levels

The most recent CCRA data identies that only 2.8% o total unding to breast cancer research is dedicated to this areao research, primarily through operating grant programs (79%).53

Current Research Activity

No current or emerging initiatives specically or breast cancer were identied in Canada or internationally. Identied

cancer-wide initiatives include: the Ontario Institute or Cancer Research Stem Cell Project (GENESIS) and the CaliorniaInstitute or Regenerative Medicine/CIHR ICR collaboration on cancer stem cell research.

Internationally, or breast cancer specically, the National Cancer Institute (NCI) has unded an RFA on the biologyo breast pre-malignancies, up to $4.5M (2008-2010). In Australia, the Priority-driven Collaborative Cancer ResearchScheme (PdCCRS) receives about $10M o unding rom Cancer Australia and the National Breast Cancer Foundation(NBCF). Projects are in place investigating all cancers in the EU, Sweden and the U.S.

Possible Research Questions

Examples o types o research within this area o enquiry include:

What is the role played by tumour-initiating cells?

What are the new cancer susceptibility genes and mutations associated with dierent subtypes o breast cancer?

What is the role played by epigenetic changes in tumour initiation and progression?

What is the impact o chromosomal integrity in breast cancer initiation?

Proposed Investment Requirements

This area was identied as needing new and more investment to encourage research (initiate and enable) throughmechanisms such as a broad competition directed to breast and other cancer tumour-initiating cells. This competitionwould include the opportunity or the unding o small teams and specic targeted initiatives, such as the impact ochromosomal instability on breast cancer development. An amount o $5-10M over ve years was proposed or each othe suggested unding mechanisms, or a total o $20M.

Chapter 6: Identiying the Research Priorities

53 The CCRA data does not distinguish between investigator-initiated research and targeted research. Thus, the percentage providedincludes grants rom both types o competitions.


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Other Characteristics

Readiness to Initiate Research:1. As there is signicant researcher expertise and capacity in Canada and GenomeCanada has invested in substantial inrastructure, this area has a high degree o readiness to initiate research.

Timing o Impact:2. Research is likely to have amedium-term impact (ve to 10 years) on patient health and thehealth system.

Uniqueness to Breast Cancer:3. The nature o the results (e.g., which gene) will determine whether they are uniqueto breast cancer.

System Support Requirements

Specic areas where improvements or changes are required to the research system to enable success include:

Inrastructure or cancer genome sequencing;

A co-ordinated and systematic approach to specimen collection and annotated clinical inormation;

Capacity training in bioinormatics and encouraging research teams to include bioinormaticians;

Support to international networks.

national framework

Documents