Acknowledgements
Amanda Spurdle is supported by an NHMRC Senior Research Fellowship, and aspects of this research were funded by Australian NHMRC Project grant ID 1010719. This work was supported in part by NIH grants CA128978 and CA116167, an NIH specialized program of research excellence in breast cancer to the Mayo Clinic (P50 CA116201), and the Breast Cancer Research Foundation. CIMBA data management was supported by Cancer Research-UK grant C12292/A11174 and C1287/A10118. ACA is a Cancer Research-UK Senior Cancer Research Fellow. BCAC data management was funded by Cancer Research UK (C1287/A10118 and C1287/A12014) and by the European Community’s Seventh Framework Programme under grant agreement 223175 (HEALTH-F2-2009-223175).
Study-specific Acknowledgements
ABCS was supported by Dutch Cancer Society grants NKI 2007-3839; 2009 4363.
ABCFS thanks Maggie Angelakos, Judi Maskiell, Gillian Dite, and Helen Tsimiklis.
The Australian Breast Cancer Tissue Bank is generously supported by the National Health and Medical Research Council of Australia, The Cancer Institute NSW, and the National Breast Cancer Foundation.
The work of the BBCC was partly funded by ELAN-Fond of the University Hospital of Erlangen.
The BBCS is funded by Cancer Research UK and Breakthrough Breast Cancer and acknowledges NHS funding to the NIHR Biomedical Research Centre, and the National Cancer Research Network (NCRN).
The work of the Breast Cancer Family Registry (BCFR) centers (BCFR-AU (ABCFS), BCFR-NC, BCFR-NY, BCFR-ON (OFBCR), BCFR-PA (FCCC), and BCFR-UT was supported by grant UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the Breast Cancer Family Registry.
BCFR-ON (OFBCR) work was additionally supported by the Canadian Institutes of Health Research “CIHR Team in Familial Risks of Breast Cancer” program.
BIDMC is supported by the Breast Cancer Research Foundation.
For BRICOH, data were collected under NIH R01 CA74415. SLN is holder of the Morris and Horowitz Families Endowed Professorship.
The BSUCH study was supported by the Dietmar-Hopp Foundation, the Helmholtz Society, and the German Cancer Research Center (DKFZ).
CBCS thanks Anne-Marie Gerdes and Bent Ejletsen for clinical data.
The CGPS was supported by the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish Medical Research Council, and Herlev Hospital. CGPS thanks staff and participants of the Copenhagen General Population Study. For the excellent technical assistance, thanks to Dorthe Uldall Andersen, Maria Birna Arnadottir, Anne Bank, and Dorthe Kjeldgård Hansen.
The Danish Breast Cancer Group (DBCG) is acknowledged for the tumor information.
The work of CNIO was partially supported by Spanish Association against Cancer (AECC08), RTICC 06/0020/1060, FISPI08/1120, Mutua Madrileña Foundation (FMMA) and SAF2010-20493.
MBCSG and CONSIT TEAM is supported by grants from the Italian Association for Cancer Research (AIRC) and by funds from the Italian citizens who allocated the 5/1,000 share of their tax payment according to Italian laws in support of the Fondazione IRCCS Istituto Nazionale Tumori to SM and of the IRCCS AOU San Martino-IST to LV and from FiorGen Foundation for Pharmacogenomics to LP. MBCSG and CONSIT TEAM thank Bernard Peissel of the Fondazione IRCCS Istituto Nazionale Tumori (INT), Milan, Italy; Laura Ottini and Giuseppe Giannini of the Sapienza University, Rome, Italy; Antonella Savarese and Aline Martayan of the Istituto Nazionale Tumori Regina Elena, Rome, Italy ; Maria Grazia Tibiletti and Daniela Furlan of the Ospedale di Circolo-Università dell’Insubria, Varese, Italy; Stefania Tommasi of the Istituto Nazionale Tumori “Giovanni Paolo II, Bari”, Italy, and Loris Bernard and the personnel of the Cogentech Cancer Genetic Test Laboratory, Milan, Italy.
The University of Westminster curates the DietCompLyf database created by and funded by Against Breast Cancer Registered Charity No. 1121258.
DKFZ are grateful to all the patients for their participation in this study.
The HEBON (j.d.lange@nki.nl) study is supported by the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756, the NWO grant 91109024, the Pink Ribbon grant 110005 and the BBMRI grant CP46/NWO. The Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON), Coordinating center: Netherlands Cancer Institute, Amsterdam, The Netherlands.
EMBRACE (dfe20@medschl.cam.ac.uk) is supported by Cancer Research UK Grants C1287/A10118 and C1287/A11990. D. Gareth Evans and Fiona Lalloo are supported by an NIHR grant to the Biomedical Research Centre, Manchester. The Investigators at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust are supported by an NIHR grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. Ros Eeles and Elizabeth Bancroft are supported by Cancer Research UK Grant C5047/A8385, Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
ESTHER was supported in part by the Baden-Württemberg State Ministry of Science, Research and Arts; and by the German Federal Ministry of Education and Research. Additional cases were recruited in the context of the VERDI study, which was supported by a grant from the German Cancer Aid (Deutsche Krebshilfe). We thank all the individuals who took part in this study and all the researchers, clinicians, technicians, and administrative staff who have enabled this work to be carried out.
The FCCC thanks Ms. JoEllen Weaver, and Dr. Betsy Bove for their technical support. The authors acknowledge support from The University of Kansas Cancer Center (P30 CA168524) and the Kansas Bioscience Authority Eminent Scholar Program. AKG was funded by 5U01CA113916, R01CA140323, and by the Chancellors Distinguished Chair in Biomedical Sciences Professorship.
GC-HBOC was kindly supported by the German Cancer Aid to R. K. Schmutzler (grant 109076). We are very thankful to all family members who participated in this study.
The GENICA (hiltrud.brauch@ikp-stuttgart.de) was funded by the Federal Ministry of Education and Research (BMBF) Germany grants 01KW9975/5, 01KW9976/8, 01KW9977/0 and 01KW0114, the Robert Bosch Foundation, Stuttgart, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), as well as the Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus Bonn, Germany. The GENICA network (Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, and University of Tübingen, Germany; (HB, Wing-Yee Lo, Christina Justenhoven), Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany (YDK, Christian Baisch), Institute of Pathology, University of Bonn, Germany (Hans-Peter Fischer), Molecular Genetics of Breast Cancer, Deutsches Krebsforschungszentrum (DKFZ) Heidelberg, Germany [Ute Hamann], Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Germany [TB, Beate Pesch, Sylvia Rabstein, Anne Lotz], Institute of Occupational Medicine and Maritime Medicine, University Medical Center Hamburg-Eppendorf, Germany [Volker Harth]). Molecular Genetics of Breast Cancer, Deutsches Krebsforschungszentrum (DKFZ), Im Neuenheimer Feld 580, 69120 Heidelberg, Germany. University of Tübingen, Geschwister-Scholl-Platz, 72074 Tübingen, Germany. Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Auerbachstraße 112, 70376 Stuttgart, Germany. Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Bürkle-de-la-Camp-Platz 1, 44789 Bochum, Germany. Institute of Occupational Medicine and Maritime Medicine, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. Institute of Pathology, Medical Faculty of the University of Bonn, Sigmund-Freud-Str. 25, Haus 372, 53127 Bonn, Germany.Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, and Johanniter Krankenhaus, Johanniterstrasse 3, 53113 Bonn, Germany.
The GESBC was supported by the Deutsche Krebshilfe e. V. [70492], and genotyping in part by the state of Baden-Württemberg through the Medical Faculty of the University of Ulm [P.685].
The HABCS study was supported by an intramural grant from Hannover Medical School.
HCSC was supported by grant RD12/0036/006. Instituto de Salud Carlos III (FEDER). Spanish Ministry of Science.
The HEBCS was financially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (266528), the Finnish Cancer Society and the Sigrid Juselius Foundation. HEBCS thanks Kirsimari Aaltonen, Karl von Smitten, and Irja Erkkilä.
IOVHBOCS was supported by Ministero dell’Istruzione, dell’Università e della Ricerca and Ministero della Salute.
Financial support for KARBAC was provided through the regional agreement on medical training and clinical research (ALF) between Stockholm City Council and Karolinska Institutet, and from the Stockholm Cancer Foundation and the Swedish Cancer Society.
The KBCP was financially supported by the special Government Funding (EVO) of Kuopio University Hospital grants, Cancer Fund of North Savo, the Finnish Cancer Organizations, the Academy of Finland, and by the strategic funding of the University of Eastern Finland.
KConFab (heather.thorne@petermac.org) is supported by grants from the National Breast Cancer Foundation, the National Health and Medical Research Council (NHMRC), and by the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania, and South Australia, and the Cancer Foundation of Western Australia. GCT is an NHMRC Senior Principal Research Fellow. RB was a Cancer Institute NSW Clinical Research Fellow. We thank Heather Thorne, Eveline Niedermayr, all the kConFab research nurses and staff, the heads and staff of the Family Cancer Clinics. Peter MacCallum Cancer Centre, 7 St Andrews Pl, East Melbourne VIC 3002, Australia.
The MARIE study was supported by the Deutsche Krebshilfe e.V. [70-2892-BR I], the Hamburg Cancer Society, the German Cancer Research Center, and the Federal Ministry of Education and Research (BMBF) Germany [01KH0402]. MARIE thanks Alina Vrieling, Katharina Buck, Muhabbet Celik, Ursula Eilber, and Sabine Behrens.
MAYO is supported by NIH grant CA128978, an NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a U.S. Department of Defense Ovarian Cancer Idea award (W81XWH-10-1-0341) and a grant from the Breast Cancer Research Foundation.
MBCSG is supported by grants from the Italian Association for Cancer Research (AIRC) and by funds from the Italian citizens who allocated the 5/1,000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects “5 × 1000”).
The MCBCS was supported by the NIH grant CA128978 and a Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201], the Breast Cancer Research Foundation and a generous gift from the David F. and Margaret T. Grohne Family Foundation and the Ting Tsung and Wei Fong Chao Foundation.
MCCS cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further supported by Australian NHMRC grants 209057, 251553 and 504711 and by infrastructure provided by Cancer Council Victoria.
The MEC was support by NIH grants CA63464, CA54281, CA098758, and CA132839.
MSKCC is supported by grants from the Breast Cancer Research Foundation and Robert and Kate Niehaus Clinical Cancer Genetics Initiative.
OBCS thank Meeri Otsukka, Kari Mononen, Jukka Moilanen, Saila Kauppila. OBCS was supported by research grants from the Finnish Cancer Foundation, the Academy of Finland Centre of Excellence grant 251314, the Sigrid Juselius Foundation, the University of Oulu, and the Oulu University Hospital Research Fund.
OFBCR was supported by grant UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the BCFR.
The ORIGO study was supported by the Dutch Cancer Society (RUL 1997-1505) and the Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL CP16).
OSU CCG thanks Leigha Senter, Kevin Sweet, Caroline Craven, and Michelle O’Conor, who were instrumental in accrual of study participants, ascertainment of medical records, and database management.
The CNIO-BCS was supported by the Genome Spain Foundation, the Red Temática de Investigación Cooperativa en Cáncer and grants from the Asociación Española Contra el Cáncer and the Fondo de Investigación Sanitario (PI11/00923 and PI081120). The Human Genotyping-CEGEN Unit (CNIO) is supported by the Instituto de Salud Carlos III. Thanks to Guillermo Pita, Charo Alonso, Daniel Herrero, Nuria Álvarez, Pilar Zamora, Primitiva Menendez, and the Human Genotyping-CEGEN Unit (CNIO).
The PBCS was supported by the Intramural Research Programs of the Division of Cancer Epidemiology and Genetics and Center for Cancer Research of the National Cancer Institute.
The pKARMA study was supported by Märit and Hans Rausings Initiative Against Breast Cancer.
POSH was supported by Cancer Research UK (grant refs A7572, A11699, C22524) and Breast Cancer Campaign 2005NOV53.
RBCS thanks Petra Bos, Jannet Blom, Ellen Crepin, Anja Nieuwlaat, Annette Heemskerk, and the Erasmus MC Family Cancer Clinic. The RBCS was funded by the Dutch Cancer Society (DDHK 2004-3124, DDHK 2009-4318).
The SASBAC study was supported by funding from the Agency for Science, Technology and Research of Singapore (A*STAR), the US National Institutes of Health (NIH), and the Susan G. Komen Breast Cancer Foundation.
SBCS thanks Sue Higham, Helen Cramp, Ian Brock, Dan Connley, and Sabapathy Balasubramanian. The SBCS was supported by Yorkshire Cancer Research S295, S299, S305PA.
SEARCH was supported by grants CRUK A490/A11021, C490/A16561.
SEARCH thanks Marie Mack and Mitul Shah.
SKKDKFZS are grateful to all the patients for their participation. We thank the physicians, other hospital staff and research assistants who contributed to the patient recruitment, data collection, and sample preparation.
SWE-BRCA collaborators are supported by the Swedish Cancer Society.
The IHCC and SZBCS studies were supported by Grant PBZ_KBN_122/P05/2004.
The UCIBCS component of this research was supported by the NIH (CA58860, CA92044) and the Lon V Smith Foundation (LVS39420).
UPENN is funded by National Institutes of Health (NIH) (R01-CA102776 and R01-CA083855; Breast Cancer Research Foundation; Susan G. Komen Foundation for the cure, Basser Research Center for BRCA.
The Women’s Cancer Program (WCP) at the Samuel Oschin Comprehensive Cancer Institute is funded by the American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN).
Authors’ contributions
ABS, FJC, and DEG conceived and designed the study. ABS and MTP coordinated data collation for analysis, and DEG performed the statistical analysis. ABS and DEG drafted the manuscript. ACA, LMcG, DB, and SH coordinated the cleaning of pathology data, risk factor data, and mutation classification for CIMBA, overseen by GC-T. MKS, MKB, and QW coordinated the collation and cleaning of pathology and risk-factor data for BCAC, overseen by DFE. FJC, RKS, BW, KR, EH, CE, A Meindl, ND, NA, HP, DN, C Sutter, SW-G, DS, SP-A, KK, RV-M, SDE, DF, RP, J Perkins, DGE, LI, RE, JA, RD, TC, GS, S Manoukian, B Bonanni, F Mariette, SF, AV, BP, LP, LV, RB, KLN, SMD, KO, AJ, NL, MT, UBJ, JR, AB, ILA, A Miron, TvOH, TC, SLN, AET, HN, MM, J Garber, AKG, AO, REF, MBT, TRR, BYK, MS, MUR, NT, PDPP, FMB, AMD, EP, P Hall, KC, MKS, AB, SC, SV, PAF, MWB, ABE, DJS, SEB, BGN, SFN, HF, JC-C, DF-J, AR, PS, KA, TAM, P Heikkila, CB, JF, SJC, L Brinton, J Lissowska, JEO, VSP, EMJ, ASW, DWW, UH, DT, HUU, TR, PD, RAEMT, C Seynaeve, CJVA, DME, WJT, LD, LJ, J Peto, IdS-S, OF, NJ, MD, R Swann, ALB, GG, AMM, GGG, RLM, L Baglietto, CM, JC, CC, R Scott, H Brauch, TB, Y-DK, AC, SSC, MWRR, J Lubinski, KJ-B, KD, J Gronwald, TD, NB, T-WP-S, P Hillemanns, CAH, BEH, FS, LLM, B Burwinkel, F Marme, HS, RY, HA-C, AZ, MJH, JMC, JWMM, MMAT-L, HB, AKD, VA, C Stegmaier, RW, KP, AJ-V, MG, AL, S Margolin, VJ, MR, RR-M, AG-N, JIA, PZ, JB, AM, VK, V-MK, JMH, PP, DZ, MB, FC, PR, S-HT, and GC-T contributed to baseline study design and recruitment of subjects included in the analysis, and provided access to genetic, epidemiologic, and pathology data from these characterized cohorts. All authors read and approved the final manuscript.