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Survivorship Research
Breast Oncology ProgramBreast Cancer: From Basics to Beyond
Lab Med 180.04
UCSF Helen Diller Family Comprehensive Cancer Center
Robert A. Hiatt, MD, PhD
11.29.10
Survivorship
• Cancer survivorship research encompasses the physical, psychosocial, and economic sequelae of cancer diagnosis and its treatment among both pediatric and adult survivors of cancer. It also includes within its domain, issues related to health care delivery, access, and follow up care, as they relate to survivors. Survivorship research focuses on the health and life of a person with a history of cancer beyond the acute diagnosis and treatment phase. It seeks to both prevent and control adverse cancer diagnosis and treatment-related outcomes such as late effects of treatment, second cancers, and poor quality of life, to provide a knowledge base regarding optimal follow-up care and surveillance of cancers, and to optimize health after cancer treatment. (NCI Office of Cancer Survivorship)
Research Topics
• Symptom Management • Complementary & Alternative Medicine • Psychosocial Care
• Complications of Therapy - late effects• Relapse and Survival• Surveillance
• Quality of Care• Health Outcomes • Economics
Priorities of NCI OCShttp://dccps.nci.nih.gov/ocs
• Chronic and Late Effects of Cancer and Its Treatment
• Interventions to Reduce Adverse Outcomes • Understanding the Role of Healthy Lifestyles and Beh
avioral• Benefit Finding and Posttraumatic Growth• Family
NCI Key Initiatives
• Physical Activity and Cancer Survivorship
• Minority & Underserved Cancer Survivors
• U.S. Prevalence Estimates
• Innovative Cancer Control in Cancer Centers
• Impact of Cancer on the Family
Research Cancer Care
UCSF Survivorship Research-Care Cycle – a positive feedback loop
2009 HDF CCC Strategic PlanMedical Center
Strategy - Expand selected clinical programs and services
Tatics- Develop and operate outpatient symptom management and psycho-oncology program using core
funding that has been provided for a 10-year period
Develop a cancer survivorship program based on a viable economic model, piloted in breast and urology, that can be expanded to serve all Cancer Center practices.
2009 HDF CCC Strategic PlanResearch
Strategy - Develop a new CCC program initiative in cancer survivorship research and
cancer health outcomes research
Tactics - Integrate research in symptom management, complimentary and alternative medicine, palliative care, and survivorship into a strong, functional CCC program within three years
Develop strategy and funding for a broad-based Cancer Survivor Cohort for persons primarily treated at the HDF CCC for use in
quality improvement and research
Survivorship Cohort(s)
• ~ 5,500 new patients per year• Questionnaire, biospecimens, informed
consent for recontact• Clinical trials• Quality improvement• Survivorship research - all types• Need strong IT infrastructure, dedicated
leadership & staff, sustainable funding• Start with breast and prostate
A Complex Systems Model of Breast Cancer Etiology
Robert A. Hiatt, MD, PhDUCSF, Epidemiology & Biostatistics
David H. Rehkopf, ScD, MPH Kaya Balke,
Travis Porco, PhD, MPH
Funded by the Special Research Initiative of the California Breast Cancer Research Program
Post Menopausal Breast Cancer
Incidence
Age at incidence
Age at menarche
Age at menopause
Breast density
High penetrance genes: (e.g., BRCA1, BRCA2, TP53)
Low penetrance genes:(e.g., CASP8, 2a35, FGFR2)
Ancestry
BIOLOGICAL
Immune function (inflammation)
Insulin resistance
New Paradigm of Breast Cancer Causation and Prevention
1234
strength of assoc(1 = strongest)
• This model is specific to incidence, not survival• Factors may differ by tumor subtype
Exit
Genotoxins
Endogenous hormones(e.g., IGF, estradiol)
123
quality of data(1 = strongest)
123
1234
Height
Post Menopausal Breast Cancer
Incidence
Radiation
Age at incidence
Environmental tobacco
PHYSICAL
Sleep disturbance
Age at menarche
Age at menopause
Breast density
High penetrance genes: (e.g., BRCA1, BRCA2, TP53)
Low penetrance genes:(e.g., CASP8, 2a35, FGFR2)
Ancestry
BIOLOGICAL
Immune function (inflammation)
Insulin resistance
New Paradigm of Breast Cancer Causation and Prevention
1234
strength of assoc(1 = strongest)
• This model is specific to incidence, not survival• Factors may differ by tumor subtype
Exit
Latitude
Endocrine disruptors(e.g., BPA, organochlorines)
Genotoxins
Endogenous hormones(e.g., IGF, estradiol)
123
quality of data(1 = strongest)
123
1234
Height
Post Menopausal Breast Cancer
Incidence
Radiation
Age at incidence
Environmental tobacco
PHYSICAL
Sleep disturbance
SOCIO/CULTURAL
Occupation
Country of Birth
Race/Ethnicity
Income
Age at menarche
Age at menopause
Breast density
High penetrance genes: (e.g., BRCA1, BRCA2, TP53)
Low penetrance genes:(e.g., CASP8, 2a35, FGFR2)
Ancestry
BIOLOGICAL
Immune function (inflammation)
Insulin resistance
New Paradigm of Breast Cancer Causation and Prevention
1234
strength of assoc(1 = strongest)
• This model is specific to incidence, not survival• Factors may differ by tumor subtype
Exit
Latitude
Education
Endocrine disruptors(e.g., BPA, organochlorines)
Genotoxins
Endogenous hormones(e.g., IGF, estradiol)
123
quality of data(1 = strongest)
123
1234
Height
Post Menopausal Breast Cancer
Incidence
Radiation
Age at incidence
Environmental tobacco
PHYSICAL
Sleep disturbance
SOCIO/CULTURAL
Occupation
Country of Birth
Race/Ethnicity
Income
HRT
Breast feeding
Age at first birth, parity
Alcohol
Obesity
Age at menarche
Age at menopause
Breast density
Tobacco use
BEHAVIORAL
High penetrance genes: (e.g., BRCA1, BRCA2, TP53)
Low penetrance genes:(e.g., CASP8, 2a35, FGFR2)
Ancestry
BIOLOGICAL
Immune function (inflammation)
Insulin resistance
New Paradigm of Breast Cancer Causation and Prevention
1234
strength of assoc(1 = strongest)
• This model is specific to incidence, not survival• Factors may differ by tumor subtype
Exit
Latitude
Phytoestrogens(e.g., soy)
Education
Endocrine disruptors(e.g., BPA, organochlorines)
Physicalactivity
Genotoxins
Endogenous hormones(e.g., IGF, estradiol)
123
quality of data(1 = strongest)
123
1234
Height
Post Menopausal Breast Cancer
Incidence
Radiation
Age at incidence
Environmental tobacco
PHYSICAL
Sleep disturbance
SOCIO/CULTURAL
Occupation
Country of Birth
Race/Ethnicity
Income
HRT
Breast feeding
Age at first birth, parity
Alcohol
Obesity
Age at menarche
Age at menopause
Breast density
Tobacco use
BEHAVIORAL
High penetrance genes: (e.g., BRCA1, BRCA2, TP53)
Low penetrance genes:(e.g., CASP8, 2a35, FGFR2)
Ancestry
BIOLOGICAL
Immune function (inflammation)
Insulin resistance
New Paradigm of Breast Cancer Causation and Prevention
1234
strength of assoc(1 = strongest)
• This model is specific to incidence, not survival• Factors may differ by tumor subtype
Exit
Latitude
Phytoestrogens(e.g., soy)
Education
Endocrine disruptors(e.g., BPA, organochlorines)
Physicalactivity
Genotoxins
Endogenous hormones(e.g., IGF, estradiol)
123
quality of data(1 = strongest)
123
1234
Lifecourse Model
Family History
Height
References
Post Menopausal Breast Cancer
Incidence
Radiation
Age at incidence
Environmental tobacco
PHYSICAL
Sleep disturbance
SOCIO/CULTURAL
Occupation
Country of Birth
Race/Ethnicity
Income
HRT
Breast feeding
Age at first birth, parity
Alcohol
Obesity
Age at menarche
Age at menopause
Breast density
Tobacco use
BEHAVIORAL
High penetrance genes: (e.g., BRCA1, BRCA2, TP53)
Low penetrance genes:(e.g., CASP8, 2a35, FGFR2)
Ancestry
BIOLOGICAL
Immune function (inflammation)
Insulin resistance
New Paradigm of Breast Cancer Causation and Prevention
• This model is specific to incidence, not survival• Factors may differ by tumor subtype
Exit
Latitude
Phytoestrogens(e.g., soy)
Education
Endocrine disruptors(e.g., BPA, organochlorines)
Physicalactivity
Genotoxins
Endogenous hormones(e.g., IGF, estradiol)
Lifecourse Model
Family History
Height
Back to Full Model
References
Post Menopausal Breast Cancer
Incidence
Radiation
Age at incidence
Environmental tobacco
PHYSICAL
Sleep disturbance
SOCIO/CULTURAL
Occupation
Country of Birth
Race/Ethnicity
Income
HRT
Breast feeding
Age at first birth, parity
Alcohol
Obesity
Age at menarche
Age at menopause
Breast density
Tobacco use
BEHAVIORAL
High penetrance genes: (e.g., BRCA1, BRCA2, TP53)
Low penetrance genes:(e.g., CASP8, 2a35, FGFR2)
Ancestry
BIOLOGICAL
Immune function (inflammation)
Insulin resistance
New Paradigm of Breast Cancer Causation and Prevention
• This model is specific to incidence, not survival• Factors may differ by tumor subtype
Exit
Latitude
Phytoestrogens(e.g., soy)
Education
Endocrine disruptors(e.g., BPA, organochlorines)
Physicalactivity
Genotoxins
Endogenous hormones(e.g., IGF, estradiol)
Lifecourse Model
Family History
Height
Back to Full Model
References
Garcia-Closas M, Chanock S. Genetic Susceptibility Loci for Breast Cancer by Estrogen Receptor Status. Clin Cancer Res 2008; 14(24), 8000-8009.
Garcia-Closas M, Hall P, Nevanlinna H et al. Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics. PLoS Genet. 2008 Apr 25;4(4):e1000054.
Post Menopausal Breast Cancer
Incidence
Radiation
Age at incidence
Environmental tobacco
PHYSICAL
Sleep disturbance
SOCIO/CULTURAL
Occupation
Country of Birth
Race/Ethnicity
Income
HRT
Breast feeding
Age at first birth, parity
Alcohol
Obesity
Age at menarche
Age at menopause
Breast density
Tobacco use
BEHAVIORAL
High penetrance genes: (e.g., BRCA1, BRCA2, TP53)
Low penetrance genes:(e.g., CASP8, 2a35, FGFR2)
Ancestry
BIOLOGICAL
Immune function (inflammation)
Insulin resistance
New Paradigm of Breast Cancer Causation and Prevention
• This model is specific to incidence, not survival• Factors may differ by tumor subtype
Exit
Latitude
Phytoestrogens(e.g., soy)
Education
Endocrine disruptors(e.g., BPA, organochlorines)
Physicalactivity
Genotoxins
Endogenous hormones(e.g., IGF, estradiol)
Lifecourse Model
Family History
Height
References
Rindfuss RR, Morgan SP, Offutt K. Education and the changing pattern of American fertility: 1963-1989. Demography 33:277-290, 1996.
Back to Full Model
Post Menopausal Breast Cancer
Incidence
Radiation
Age at incidence
Environmental tobacco
PHYSICAL
Sleep disturbance
SOCIO/CULTURAL
Occupation
Country of Birth
Race/Ethnicity
Income
HRT
Breast feeding
Age at first birth, parity
Alcohol
Obesity
Age at menarche
Age at menopause
Breast density
Tobacco use
BEHAVIORAL
High penetrance genes: (e.g., BRCA1, BRCA2, TP53)
Low penetrance genes:(e.g., CASP8, 2a35, FGFR2)
Ancestry
BIOLOGICAL
Immune function (inflammation)
Insulin resistance
New Paradigm of Breast Cancer Causation and Prevention
• This model is specific to incidence, not survival• Factors may differ by tumor subtype
Exit
Latitude
Phytoestrogens(e.g., soy)
Education
Endocrine disruptors(e.g., BPA, organochlorines)
Physicalactivity
Genotoxins
Endogenous hormones(e.g., IGF, estradiol)
Lifecourse Model
Family History
Height
Back to Full Model
Family History
1234
strength of assoc(1 = strongest)
123
quality of data(1 = strongest)
123
1234
Endogenous hormones(e.g., IGF, estradiol)Endogenous hormones(e.g., IGF, estradiol)
Radiation
Endocrine disruptors(e.g., BPA, organochlorines)
Environmental tobacco
Genotoxins
Insulin resistance
Immune function (inflammation)
Breast feeding
Age at first birth, parity
Post Menopausal Breast Cancer
Incidence
Radiation
Age at incidence
Environmental tobacco
PHYSICAL
Sleep disturbance
SOCIO/CULTURAL
Occupation
Country of Birth
Race/Ethnicity
Income
HRT
Breast feeding
Age at first birth, parity
Alcohol
Obesity
Age at menarche
Age at menopause
Breast density
Tobacco use
High penetrance genes: (e.g., BRCA1, BRCA2, TP53)
Low penetrance genes:(e.g., CASP8, 2a35, FGFR2)
Ancestry
BIOLOGICAL
Immune function (inflammation)
Insulin resistance
New Paradigm of Breast Cancer Causation and Prevention
Exit
Latitude
Phytoestrogens(e.g., soy)
Education
Endocrine disruptors(e.g., BPA, organochlorines)
Physicalactivity
Genotoxins
Lifecourse Model
Family History
Height
Back to Full Model
Lifecourse Model
prenatal
early childhood/pre-puberty
puberty
pregnancy
pre-menopausal
(post) menopausal
Multiple life stages
Questions?
