Robert A. Hiatt, MD, PhD 11.29.10

1. Survivorship ResearchBreast Oncology ProgramBreast Cancer: From Basics to BeyondLab Med 180.04UCSF Helen Diller Family Comprehensive Cancer Center Robert A. Hiatt, MD, PhD 11.29.10

2. 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)

3. Research Topics • Symptom Management • Complementary & Alternative Medicine • Psychosocial Care • Complications of Therapy - late effects • Relapse and Survival • Surveillance • Quality of Care • Health Outcomes • Economics

4. 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 Behavioral • Benefit Finding and Posttraumatic Growth • Family

5. 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

6. UCSF Survivorship Research-Care Cycle – a positive feedback loop Research Cancer Care

7. 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.

8. 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

9. 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

10. A Complex Systems Model of Breast Cancer Etiology Robert A. Hiatt, MD, PhD UCSF, 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

11. strength of assoc(1 = strongest) 1 2 3 4 quality of data(1 = strongest) 1 2 3 1 2 3 New Paradigm of Breast Cancer Causation and Prevention Post Menopausal Breast Cancer Incidence Genotoxins Age at incidence Breast density Height High penetrance genes: (e.g., BRCA1, BRCA2, TP53) Age at menopause Endogenous hormones(e.g., IGF, estradiol) Low penetrance genes:(e.g., CASP8, 2a35, FGFR2) Immune function (inflammation) 1 2 3 4 Age at menarche Insulin resistance Ancestry BIOLOGICAL Exit • This model is specific to incidence, not survival • Factors may differ by tumor subtype

12. strength of assoc(1 = strongest) 1 2 3 4 quality of data(1 = strongest) 1 2 3 1 2 3 New Paradigm of Breast Cancer Causation and Prevention PHYSICAL Latitude Environmental tobacco Sleep disturbance Endocrine disruptors(e.g., BPA, organochlorines) Radiation Post Menopausal Breast Cancer Incidence Genotoxins Age at incidence Breast density Height High penetrance genes: (e.g., BRCA1, BRCA2, TP53) Age at menopause Endogenous hormones(e.g., IGF, estradiol) Low penetrance genes:(e.g., CASP8, 2a35, FGFR2) Immune function (inflammation) 1 2 3 4 Age at menarche Insulin resistance Ancestry BIOLOGICAL Exit • This model is specific to incidence, not survival • Factors may differ by tumor subtype

13. strength of assoc(1 = strongest) 1 2 3 4 quality of data(1 = strongest) 1 2 3 1 2 3 New Paradigm of Breast Cancer Causation and Prevention SOCIO/CULTURAL PHYSICAL Country of Birth Latitude Education Environmental tobacco Sleep disturbance Occupation Endocrine disruptors(e.g., BPA, organochlorines) Race/Ethnicity Radiation Income Post Menopausal Breast Cancer Incidence Genotoxins Age at incidence Breast density Height High penetrance genes: (e.g., BRCA1, BRCA2, TP53) Age at menopause Endogenous hormones(e.g., IGF, estradiol) Low penetrance genes:(e.g., CASP8, 2a35, FGFR2) Immune function (inflammation) 1 2 3 4 Age at menarche Insulin resistance Ancestry BIOLOGICAL Exit • This model is specific to incidence, not survival • Factors may differ by tumor subtype

14. strength of assoc(1 = strongest) 1 2 3 4 quality of data(1 = strongest) 1 2 3 1 2 3 New Paradigm of Breast Cancer Causation and Prevention SOCIO/CULTURAL PHYSICAL Country of Birth Latitude Education Environmental tobacco Sleep disturbance Occupation Endocrine disruptors(e.g., BPA, organochlorines) Race/Ethnicity Radiation Income Breast feeding HRT Post Menopausal Breast Cancer Incidence Alcohol Genotoxins Phytoestrogens(e.g., soy) Age at first birth, parity Age at incidence Physicalactivity Breast density Height High penetrance genes: (e.g., BRCA1, BRCA2, TP53) Tobacco use Age at menopause Endogenous hormones(e.g., IGF, estradiol) Low penetrance genes:(e.g., CASP8, 2a35, FGFR2) Obesity Immune function (inflammation) 1 2 3 4 Age at menarche Insulin resistance BEHAVIORAL Ancestry BIOLOGICAL Exit • This model is specific to incidence, not survival • Factors may differ by tumor subtype

15. strength of assoc(1 = strongest) 1 2 3 4 quality of data(1 = strongest) 1 2 3 1 2 3 New Paradigm of Breast Cancer Causation and Prevention SOCIO/CULTURAL PHYSICAL Country of Birth Latitude Education Environmental tobacco Sleep disturbance Occupation Endocrine disruptors(e.g., BPA, organochlorines) Race/Ethnicity Radiation Income Breast feeding HRT Post Menopausal Breast Cancer Incidence Alcohol Genotoxins Phytoestrogens(e.g., soy) Age at first birth, parity Age at incidence Physicalactivity Breast density Height High penetrance genes: (e.g., BRCA1, BRCA2, TP53) Tobacco use Age at menopause Endogenous hormones(e.g., IGF, estradiol) Low penetrance genes:(e.g., CASP8, 2a35, FGFR2) Obesity Immune function (inflammation) 1 2 3 4 Age at menarche Insulin resistance BEHAVIORAL Ancestry BIOLOGICAL Lifecourse Model Family History References Exit • This model is specific to incidence, not survival • Factors may differ by tumor subtype

16. New Paradigm of Breast Cancer Causation and Prevention References SOCIO/CULTURAL PHYSICAL Country of Birth Latitude Education Environmental tobacco Sleep disturbance Occupation Endocrine disruptors(e.g., BPA, organochlorines) Race/Ethnicity Radiation Income Breast feeding HRT Post Menopausal Breast Cancer Incidence Alcohol Genotoxins Phytoestrogens(e.g., soy) Age at first birth, parity Age at incidence Physicalactivity Breast density Height High penetrance genes: (e.g., BRCA1, BRCA2, TP53) Tobacco use Age at menopause Endogenous hormones(e.g., IGF, estradiol) Low penetrance genes:(e.g., CASP8, 2a35, FGFR2) Obesity Immune function (inflammation) Age at menarche Insulin resistance BEHAVIORAL Ancestry BIOLOGICAL Lifecourse Model Family History Back to Full Model Exit • This model is specific to incidence, not survival • Factors may differ by tumor subtype

17. New Paradigm of Breast Cancer Causation and Prevention References SOCIO/CULTURAL PHYSICAL Country of Birth Latitude Education Environmental tobacco Sleep disturbance Occupation Endocrine disruptors(e.g., BPA, organochlorines) Race/Ethnicity Radiation Income Breast feeding HRT Post Menopausal Breast Cancer Incidence Alcohol Genotoxins Phytoestrogens(e.g., soy) Age at first birth, parity Age at incidence 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. Physicalactivity Breast density Height High penetrance genes: (e.g., BRCA1, BRCA2, TP53) Tobacco use Age at menopause Endogenous hormones(e.g., IGF, estradiol) Low penetrance genes:(e.g., CASP8, 2a35, FGFR2) Obesity Immune function (inflammation) Age at menarche Insulin resistance BEHAVIORAL Ancestry BIOLOGICAL Lifecourse Model Family History Back to Full Model Exit • This model is specific to incidence, not survival • Factors may differ by tumor subtype

18. New Paradigm of Breast Cancer Causation and Prevention References SOCIO/CULTURAL PHYSICAL Country of Birth Latitude Education Environmental tobacco Sleep disturbance Occupation Endocrine disruptors(e.g., BPA, organochlorines) Race/Ethnicity Radiation Income Breast feeding HRT Rindfuss RR, Morgan SP, Offutt K. Education and the changing pattern of American fertility: 1963-1989. Demography 33:277-290, 1996. Post Menopausal Breast Cancer Incidence Alcohol Genotoxins Phytoestrogens(e.g., soy) Age at first birth, parity Age at incidence Physicalactivity Breast density Height High penetrance genes: (e.g., BRCA1, BRCA2, TP53) Tobacco use Age at menopause Endogenous hormones(e.g., IGF, estradiol) Low penetrance genes:(e.g., CASP8, 2a35, FGFR2) Obesity Immune function (inflammation) Age at menarche Insulin resistance BEHAVIORAL Ancestry BIOLOGICAL Lifecourse Model Family History Back to Full Model Exit • This model is specific to incidence, not survival • Factors may differ by tumor subtype

19. strength of assoc(1 = strongest) 1 2 3 4 quality of data(1 = strongest) 1 2 3 1 2 3 New Paradigm of Breast Cancer Causation and Prevention Family History SOCIO/CULTURAL PHYSICAL Country of Birth Latitude Education Environmental tobacco Sleep disturbance Occupation Endocrine disruptors(e.g., BPA, organochlorines) Race/Ethnicity Radiation Income Breast feeding HRT Post Menopausal Breast Cancer Incidence Alcohol Genotoxins Phytoestrogens(e.g., soy) Age at first birth, parity Age at incidence Physicalactivity Breast density Height High penetrance genes: (e.g., BRCA1, BRCA2, TP53) Tobacco use Age at menopause Endogenous hormones(e.g., IGF, estradiol) Low penetrance genes:(e.g., CASP8, 2a35, FGFR2) Obesity Immune function (inflammation) 1 2 3 4 Age at menarche Insulin resistance BEHAVIORAL Ancestry BIOLOGICAL Lifecourse Model Family History Back to Full Model Exit • This model is specific to incidence, not survival • Factors may differ by tumor subtype

20. New Paradigm of Breast Cancer Causation and Prevention Lifecourse Model SOCIO/CULTURAL PHYSICAL Country of Birth Latitude Education Environmental tobacco Environmental tobacco Sleep disturbance Occupation Endocrine disruptors(e.g., BPA, organochlorines) Endocrine disruptors(e.g., BPA, organochlorines) Race/Ethnicity Radiation Radiation Income Breast feeding Breast feeding HRT Post Menopausal Breast Cancer Incidence Alcohol Genotoxins Genotoxins Phytoestrogens(e.g., soy) Age at first birth, parity Age at first birth, parity Age at incidence Physicalactivity Breast density Height High penetrance genes: (e.g., BRCA1, BRCA2, TP53) Tobacco use Age at menopause Endogenous hormones(e.g., IGF, estradiol) Endogenous hormones(e.g., IGF, estradiol) prenatal Low penetrance genes:(e.g., CASP8, 2a35, FGFR2) Obesity Immune function (inflammation) Immune function (inflammation) early childhood/pre-puberty Age at menarche puberty Insulin resistance Insulin resistance pregnancy pre-menopausal Ancestry (post) menopausal BIOLOGICAL Multiple life stages Lifecourse Model Family History Back to Full Model Exit

21. Questions?