Organization and Communication: The W omen’s E nvironment, C ancer a nd R adiation E pidemiology (WECARE) Study

1. Organization and Communication: The Women’s Environment, Cancer and Radiation Epidemiology (WECARE) Study Jonine Bernstein, Ph.D.

2. WECARE Study Overview Purpose To examine the interaction of radiation exposure and genetic susceptibility in the etiology of second primary breast cancer. Hypothesis A woman who carries a mutant variant in one of the genes under study will be more susceptible to radiation-induced cancer than a woman who is not a carrier. Design Population-based, case-control study • Cases are women with bilateral breast cancer • Controls are women with unilateral breast cancer (Bernstein, … , Thompson, Br Ca Res 2004)

3. Data Sources

4. WECARE Study Design Cases (n=708) • Diagnosed since 1/1/1985 with incidentbreast cancer • Diagnosed since 1/1/1986 with contralateral breast cancer • One year or longer time lag between primaries • Under age 55 at diagnosis of the first primary • No other cancer diagnosis • Alive

5. WECARE Study Design Controls(n=1397) • With unilateral breast cancer • Individually matched 2:1 to cases on: • Registry • Age (5 year) • Diagnosis date of breast cancer (4 year) • Race • No other cancer diagnosis • Counter-matched on radiotherapy status • 2:1 (RRT+: RRT -)

6. WECARE Study Data Collection • Women identified through 5 population-based cancer registries (US and Denmark) • Telephone interview using a structured questionnaire • During home visits, a blood sample drawn by a study phlebotomist

7. Medical Treatment Information and Data for Radiation Dosimetry • Sources • Treatment and tumor characteristics information collected registry records • Hospital charts • Pathology/surgery reports • Doctor office /mammography records • Radiation oncology files • Missing Data • ~ 7% patient records inadequate for dosimetry • ~ 2% participants have all documentation missing

8. Contralateral Breast Dose (cGy): Mean and Range among Patients Treated with Breast Irradiation (1488 patients)

9. Laboratory Screening • Genetic Analyses • Conducted in 5 labs for all 2100 WECARE Study participants (US, Norway, and Sweden) • Staged approach: DHPLC followed by direct sequencing • All conditions, primers standardized across labs • Inter- and Intra-lab QC implemented (Bernstein, … , Concannon, Hum Mut 2003)

10. WECARE Study Organization

11. USC MSKCC USM UTMDACC VU NYU WECARE Study Working Groups: Field Organization DCS SEER Sites USC FHCRC UCI IOWA Laboratories Data Collection Centers BRI NRH USC LUND UCLA MSSM Coordinating Center NCI Program Officer External Advisory Committee Internal Advisory Epidemiological/ Biostatistical Methods Radiation Dosimetry Cell Line Prep/Biorepository Data Management Coriell DCS USC MSKCC MSKCC

12. WECARE Study Working Subcommittees Data & Biorepository Use Rotating Membership Publications Rotating Membership Allocation of Specimens and Lab Protocol Review Fixed Membership Steering Committee All PIs and Key Investigators Internal Advisory Fixed Membership Data Analysis Centrally Coordinated/All invited Budget Fixed Membership Derived Variables Centrally Coordinated/ All Invited

13. WECARE Study Collaborative Group Coordinating Center Jonine Bernstein MSKCC Xiaolin Liang MSKCC Abigail Wolitzer MSKCC Internal Advisors Leslie Bernstein Robert Haile Pat Conconnan WD Thompson Data Collection Leslie Bernstein USC Laura Donnelly USC Valerie Zayas USC Kathy Lane USC Jane Sullivan-Halley USC Jorgen Olsen DCS Lene Mellemkjaer DCS Helle Clement Petersen DCS Lisbeth Bertelsen DCS Michael Andersson DCS Kathleen Malone FHCRC Noemi Epstein FHCRC Heather Jurado FHCRC Hoda Anton-Culver UCI Joan Largent UCI Kay Bergdahl UCI Chuck Lynch Iowa Jeanne DeWall Iowa Lori Odle Iowa Methods Duncan Thomas USC W. Douglas Thompson USM Bryan Langholz USC Xinbo Zhang USC Yaping Wang USC Colin Begg MSKCC Marinela Capanu MSKCC Amanda Hummer MSKCC Laboratory Pat Concannon BRI Sharon Teraoka BRI Eric Olson BRI Robert Haile USC Anh Diep USC Yong Liu USC Nianmin Zhou USC Shanyan Xue USC Andre Hernandez USC Evgenia Ter-Karapetova USC Anne-Lise Borresen-Dale NRH Laila Jasen NRH Olaug Rodningen NRH Ake Borg Lund Therese Sandberg Lund Lina Johansson Lund Barry Rosenstein MSSM David Atencio MSSM Per Guldberg DCS Radiation Dosimetry Marilyn Stovall MDAAC Susan Smith MDACC Roy Shore NYU Repository Jeanne Beck Coriell Rick Martinas Coriell Anh Diep USC Yong Liu USC Irene Orlow MSKCC Consultants Richard Gatti UCLA Elaine Ostrander NIH John Boice, Jr. VU External Advisors Alice Whittemore Stanford Jack Schull UTH Bruce Ponder Cambridge Program Officer Daniela Seminara NCI

14. WECARE Study Communication

15. Communication Through-out Study • Working Group Communication during field work-Constant • Within Group • Bi-monthly conference calls • Monthly data delivery and progress reports • Dedicated web-site • Between Group • Annual/ semi-annual key investigator meetings

16. Central Informatics Management System Functional domains • Tracking database – every phase and every aspect of study on individual level and triplet level • Database for storage, cleaning and maintain data acquired through data collection instruments • Mutation screening database – screening process and results • Long term storage and access • Secures confidentiality CIMS links and maintains data from all sources and tracks all information so it is instantly available.

17. Tracking database-Data Collection

18. Production Report 1

19. WECARE Study Informatics

20. WECARE Study Informatics

21. WECARE Study Informatics

22. WECARE Study Informatics

23. Summary: Challenges • Study set up is key– anticipate the type of informatics that will be needed and plan ahead; • Involve trained personnel, including informatics specialists, data managers and editors (for both lab and epi data); • Over-communicate throughout the study, especially if the study involves scientists from diverse geographic regions; • Plan in advance to maintain the infrastructure, even as the study is winding down.