1. Survivorship Research Breast Oncology Program Breast Cancer: From Basics to Beyond Lab Med 180.04 UCSF 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 OCS http://dccps.nci.nih.gov/ocs Chronic and Late Effects of Cancer and Its TreatmentChronic and Late Effects of Cancer and Its Treatment Interventions to Reduce Adverse Outcomes Understanding the Role of Healthy Lifestyles and BehavioralUnderstanding 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. Research Cancer Care UCSF Survivorship Research-Care Cycle – a positive feedback loop

7. 2009 HDF CCC Strategic Plan Medical 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 Plan Research 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. 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 12341234 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) Physical activity Genotoxins Endogenous hormones (e.g., IGF, estradiol) 123123 quality of data (1 = strongest) 123123 12341234 Lifecourse Model Family History Height

12. 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 12341234 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) Physical activity Genotoxins Endogenous hormones (e.g., IGF, estradiol) 123123 quality of data (1 = strongest) 123123 12341234 Lifecourse Model Family History Height

13. 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 12341234 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) 123123 quality of data (1 = strongest) 123123 12341234 Height

14. 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 12341234 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) 123123 quality of data (1 = strongest) 123123 12341234 Height

15. 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 12341234 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) 123123 quality of data (1 = strongest) 123123 12341234 Height

16. 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 12341234 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) Physical activity Genotoxins Endogenous hormones (e.g., IGF, estradiol) 123123 quality of data (1 = strongest) 123123 12341234 Height

17. 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 12341234 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) Physical activity Genotoxins Endogenous hormones (e.g., IGF, estradiol) 123123 quality of data (1 = strongest) 123123 12341234 Lifecourse Model Family History Height References

18. 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) Physical activity Genotoxins Endogenous hormones (e.g., IGF, estradiol) Lifecourse Model Family History Height Use for making new slides References

19. 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) Physical activity Genotoxins Endogenous hormones (e.g., IGF, estradiol) Lifecourse Model Family History Height Back to Full Model References

20. 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) Physical activity 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.

21. 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) Physical activity 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

22. 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) Physical activity Genotoxins Endogenous hormones (e.g., IGF, estradiol) Lifecourse Model Family History Height Back to Full Model Family History 12341234 strength of assoc (1 = strongest) 123123 quality of data (1 = strongest) 123123 12341234

23. 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) Physical activity 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

24. Questions?