Community Participation in Cancer Discovery Research: Linking Biology, Cancer Disparities, and Dissemination

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1 Community Participation in Cancer Discovery Research: Linking Biology, Cancer Disparities, and Dissemination Robert A. Hiatt UCSF Helen Diller Family Comprehensive Cancer Center July 13, 2011 Bethesda, MD

2 Question? How can basic research on the origins of cancer disparities be 1) better understood by the public and 2) better disseminated to the people who are intended to benefit from the results?

3 Community Participation Community Based Participatory Research (CBPR) is not new, but its application to discovery research is unusual. For cancer disparities research that takes a transdisciplinary approach and seeks to integrate basic biologic understanding into a fuller picture of its origins, dissemination can be a challenge.

4 Community Participation How can community participation be integrated into cancer disparities research for the benefit of science and the public health? An example from the Breast Cancer and the Environment Research Centers, an NCI/NIEHS sponsored national network.

5 The Breast Cancer and the Environment Research Centers

6 Research Question Do environmental factors contribute to the etiology of breast cancer in humans?

7 What evidence motivates this question?

8 Female Breast Cancer Incidence Rates age-standardized rates, Cases/100,000 p-yrs From Parkin, et al., IARC, 1997

9 Variation in Breast Cancer Rates, Japanese age-standardized incidence rates, Cases/100,000 p-yrs From Parkin, et al., IARC, 1997

10 Research Approaches Mechanistic. Animal studies Epidemiology

11 Epidemiologic Studies Most have been performed in adults Study designs have followed case-control or cohort approaches. Some natural experiments

12 Selected Factors Known to Influence Breast Cancer Risk Factor Comparison RR 95% CI Age at menarche 15 vs. <12 y 0.72 ( ) Parity 3 vs. none 0.72 ( ) Age at First Birth >30 vs. 20 y 1.46 ( ) Education >HS vs. <HS 1.08 ( ) BBD Yes vs. No 1.53 ( ) Maternal History Yes vs. No 1.38 ( ) Sister History Yes vs. No 1.47 ( ) From Hunter DJ, et al. Cancer Causes Control 1997;8: Analysis includes 322,647 women followed for 5-7 years, with 4,827 incident cases of breast cancer.

13 Seasons of Life & Breast Cancer Risk In utero: birthweight; in utero exposures? Infancy: infant feeding practices? Early childhood: growth patterns? Adolescence: earlier age at menarche increases risk Young adulthood: late age at first birth increases risk Childbearing years: greater parity decreases risk; breastfeeding decreases risk Menopausal transition: late menopause increases risk; use of HRT increases risk Postmenopausal years: lifetime body weight patterns influence risk

14 Has led to more interest in windows of susceptibility

15 Puberty Reasons for interest as a window of susceptibility: Time of rapid development of both epithelial cells and stroma. Period of rapid growth in height. Age of menarche highly variable internationally Age of menarche dropping over last century with industrialization

16 The Changing Age of Puberty Over Time

17 International Trends in Age at Menarche

18 Korean example Cho GJ et al. Eur J Pediatrics 2010

19 Prevalence of Breast Development at Tanner Stage 2 or Greater by Age and Race Herman-Giddens et al., Pediatrics, 1997

20 Height & Breast Cancer Pooled Analysis, Cohort Studies of Diet & Breast Cancer Pooled RR = 1.25 ( ) Relative Risk, Height (m) 1.68 vs <1.6 Cohort from van den Brandt, et al., Am J Epidemiol, 2000

21 Median Age at Maturation Milestones NHLBI Growth and Health Study, Biro et al., Pediatrics, 2006

22 New Approach Age at menarche an established risk factor Puberty a time of rapid breast development Changing age for initiation of puberty -likely due to environmental factors So Take a life-course approach Focus on early development

23 Bay Area Breast Cancer & Environment Research Center PI: Project 1: Robert A. Hiatt, MD, PhD, UCSF CCC Environmental Effects on the Molecular Architecture and Function of the Mammary Gland across the Lifespan. PI: Zena Werb, PhD, UCSF Project 2: Environmental and Genetic Determinants of Puberty PI: Lawrence Kushi, ScD, KP/DOR COTC: Community Outreach and Translation Core PI: Janice Barlow, RN, Zero Breast Cancer

24 Breast Cancer and the Environment Research Centers (BCERCs) Marin County DHHS Zero Breast Cancer UCSF California Department of Health Services LBNL Kaiser Permanente Michigan State University University of Michigan University of Cincinnati Cincinnati Children s Hospital Roswell Park Cancer Institute NCI NIEHS Mount Sinai School of Medicine Fox Chase Cancer Center University of Alabama Funding Agencies BCERC Prime Institutions Collaborating Institutions

25 Project 1 - Specific Aims Specific Aim 1: Determine the alterations in the mammary microenvironment and the mammary cells in normal and cancer prone mice in vivo during prenatal development, pubertal branching morphogenesis, pregnancy and aging. Specific Aim 2: Determine the effects of exposure to prototypical environmental stressors during prenatal development, pubertal branching morphogenesis, pregnancy and aging on the mammary gland in normal and cancer prone mice in vivo Specific Aim 3: Determine the effects of environmental agents implicated from studies in Project 2 on regulating the mammary microenvironment of mammary cells during branching morphogenesis Specific Aim 4: Validate the animal experiments by determining how these environmental stressors affect human mammary epithelial cells in culture through the telomere crisis, comparing the critical endpoints derived from the animal.

26 Distinct mechanisms pattern the mammary gland Lateral branching TEB invasion Dichotomous branching Adapted from Wiseman & Werb (2002) Science

27 Mammary Development lymph node 3 wks nipple 5 wks 11 wks nipple Cap cells Luminal (Keratin 8/18) Myoepithelial (Keratin 5/14) Mature Duct Body cells Terminal End Bud

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30 BCERC Epidemiology Study Populations Healthy girls age 6-8 yrs at time of recruitment California: Ohio: Bay area KPNC members Larry Kushi, PI, Division of Research, Kaiser Permanente Northern California Cincinnati-area school districts Frank Biro, PI, Cincinnati Children s Hospital New York: East Harlem neighborhood clinics Mary Wolff, PI, Mount Sinai School of Medicine

31 Methods Food intake Physical activity Environmental exposures Medical and related history Psychosocial measures Demographics Anthropometry Biospecimens Tanner Staging

32 Puberty Tanner Staging

33 Tempo (Pace, B2 Menarche) B2 9 y 10 y Menarche 12 y 13 y Tempo 3 y 2 y 3 y Age (years)

34 Cohort study of Young Girls Nutrition, Environment & Transitions A Project of the Bay Area Breast Cancer and the Environment Research Center

35 CYGNET Study Population Born in and currently a member of Kaiser Permanente Resident at birth and currently of Marin County, San Francisco, and selected East Bay communities (e.g., Richmond, El Cerrito, Berkeley, Oakland) in western Contra Costa and Alameda Counties Age 6 or 7 yrs at time of recruitment

36 KP San Rafael KP San Francisco KP DOR

37 Results to Date

38 Breast Maturation Status, age 7 years BCERP Puberty Studies, Biro et al., Pediatrics, 2010 Group MSSM Cincinnati KPNC Total B1 B2+ (%) B1 B2+ (%) B1 B2+ (%) B1 B2+ (%) Black (28.7) (31.3) (25.7) (23.4) Hispanic (17.6) 10 1 (9.1) (11.2) (14.9) Asian 4 0 (0.0) 40 1 (2.4) 44 1 (2.2) White (13.6) (6.8) (10.4)

39 Breast Maturation Status, age 8 years BCERP Puberty Studies, Biro et al., Pediatrics, 2010 Group MSSM Cincinnati KPNC Total B1 B2+ (%) B1 B2+ (%) B1 B2+ (%) B1 B2+ (%) Black (11.7) (51.8) (30.4) (42.9) Hispanic (38.2) 8 4 (33.3) (18.8) (30.9) Asian 4 0 (0.0) 34 6 (15.0) 38 6 (13.6) White (26.7) (7.3) (18.3)

40 Breast Development in the BCERP Puberty Studies (Biro, 2010) and PROS (Herman-Giddens, 1997) Age 7 y Age 8 y

41 Father absence and breast development adjusted for BMI Deardorff, et al., J Adol Health 2011 Income category Higher income, $75,000/year Lower income, <$75,000/year B2 onset All RR (95% CI) PH2 onset - AA RR (95% CI) 2.4 ( ) 4.6( ) 0.8 ( ) 1.1(.5-2.6)

42 A Transdisciplinary Approach

43 Policy Neighborhoods Workplace METABOLOME PROTEOME TRANSCRIPTOME GENOME Exercise Smoking Diet

44 TDS Conceptual Model Life-course approach Multiple levels of analysis (social ecologic model) Stages of carcinogenesis Must incorporate aims of constituent investigators and collaborators Demonstrate hypotheses Predictive value

45 Life-course Approach Pre-natal Early childhood Pre-puberty Pregnancy Pre-menopause Menopause Post-menopause

46 Levels of Analysis Gene Cell Tissue/Organ Individual Family Neighborhood/City Society

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49 Dissemination Activities Community meetings - bidirectional exchange (e.g., Town Halls, Tea Talks) Fact sheets on chemical exposures and puberty Communication (e.g., videos) Recruitment and retention Evaluation

50 COTC Collaborations with Biology Hands-on Laboratory Training for Advocates Modeling Breast Cancer and the Environment Report DVD Of Mice and Women DVD The Breast Biologues

51 Of Mice and Women: Modeling Breast Cancer and the Environment An innovative educational tool to engage the community on why mouse models are used in breast cancer research Developed by the Bay Area Breast Cancer and Environment Research Center, Community Outreach and Translation Core in partnership with Dr. Mary Helen Barcellos-Hoff, PhD, co-investigator, Project 1

52 The Breast Biologues: A biology dialogue about breast cancer and the environment A new education kit that explains how the breast develops and how exposures to potential cancer-causing chemicals at specific times during development might influence future breast cancer risk. Developed by the Bay Area Breast Cancer and Environment Research Center, Community Outreach and Translation Core in partnership with Lori Schkufza, an animation consultant; the BABCERC basic science researchers: Dr. Zena Werb at University of California San Francisco, Dr. Paul Yaswen at Lawrence Berkeley National Laboratory, and Dr. Mary Helen Barcellos-Hoff at New York University Langone School of Medicine.

53 COTC Collaborations with Epidemiology Target Populations 1. Study Participants Recruitment and Retention Newsletters, Community Meetings Returning Individual Level Results

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55 COTC Collaborations with Epidemiology 2. Pediatricians PARDNER grant: Partnerships for the Dissemination of New Results.

56 COTC Collaborations with Epidemiology 3. Lay Public Community Participation Town Hall Meetings Resource Tables Presentations Public Health Messages

57 How can we create effective messages/tools/interventions that integrate findings from genetic, cellular, animal and human studies?

58 Public Health Messages Purpose: To synthesize the BCERC biological, toxicologic, and epidemiologic research results into integrated messages at appropriate education levels that can be broadly disseminated to affected communities To identify key messages integrating the body of peer reviewed research derived from the BCERC network To identify strategies for developing key messages for affected communities To develop a well designed dissemination plan for the key messages developed

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61 Public Health Messages Challenges: Are findings from the laboratory relevant for human populations? When are findings consistent enough to warrant dissemination? How can we evaluate the impact of the findings on final endpoints? What messages do we want to prioritize for the lay public? How do findings translate so they have utility for members of the lay public?

62 FIN

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