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Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers.

Abstract The clinical management of BRCA1 and BRCA2 mutation carriers requires accurate, prospective cancer risk estimates.
PMID
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Authors

Mayor MeshTerms
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Journal Title jama
Publication Year Start




PMID- 28632866
OWN - NLM
STAT- In-Process
DA  - 20170620
LR  - 20170620
IS  - 1538-3598 (Electronic)
IS  - 0098-7484 (Linking)
VI  - 317
IP  - 23
DP  - 2017 Jun 20
TI  - Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2
      Mutation Carriers.
PG  - 2402-2416
LID - 10.1001/jama.2017.7112 [doi]
AB  - Importance: The clinical management of BRCA1 and BRCA2 mutation carriers requires
      accurate, prospective cancer risk estimates. Objectives: To estimate age-specific
      risks of breast, ovarian, and contralateral breast cancer for mutation carriers
      and to evaluate risk modification by family cancer history and mutation location.
      Design, Setting, and Participants: Prospective cohort study of 6036 BRCA1 and
      3820 BRCA2 female carriers (5046 unaffected and 4810 with breast or ovarian
      cancer or both at baseline) recruited in 1997-2011 through the International
      BRCA1/2 Carrier Cohort Study, the Breast Cancer Family Registry and the Kathleen 
      Cuningham Foundation Consortium for Research into Familial Breast Cancer, with
      ascertainment through family clinics (94%) and population-based studies (6%). The
      majority were from large national studies in the United Kingdom (EMBRACE), the
      Netherlands (HEBON), and France (GENEPSO). Follow-up ended December 2013; median 
      follow-up was 5 years. Exposures: BRCA1/2 mutations, family cancer history, and
      mutation location. Main Outcomes and Measures: Annual incidences, standardized
      incidence ratios, and cumulative risks of breast, ovarian, and contralateral
      breast cancer. Results: Among 3886 women (median age, 38 years; interquartile
      range [IQR], 30-46 years) eligible for the breast cancer analysis, 5066 women
      (median age, 38 years; IQR, 31-47 years) eligible for the ovarian cancer
      analysis, and 2213 women (median age, 47 years; IQR, 40-55 years) eligible for
      the contralateral breast cancer analysis, 426 were diagnosed with breast cancer, 
      109 with ovarian cancer, and 245 with contralateral breast cancer during
      follow-up. The cumulative breast cancer risk to age 80 years was 72% (95% CI,
      65%-79%) for BRCA1 and 69% (95% CI, 61%-77%) for BRCA2 carriers. Breast cancer
      incidences increased rapidly in early adulthood until ages 30 to 40 years for
      BRCA1 and until ages 40 to 50 years for BRCA2 carriers, then remained at a
      similar, constant incidence (20-30 per 1000 person-years) until age 80 years. The
      cumulative ovarian cancer risk to age 80 years was 44% (95% CI, 36%-53%) for
      BRCA1 and 17% (95% CI, 11%-25%) for BRCA2 carriers. For contralateral breast
      cancer, the cumulative risk 20 years after breast cancer diagnosis was 40% (95%
      CI, 35%-45%) for BRCA1 and 26% (95% CI, 20%-33%) for BRCA2 carriers (hazard ratio
      [HR] for comparing BRCA2 vs BRCA1, 0.62; 95% CI, 0.47-0.82; P=.001 for
      difference). Breast cancer risk increased with increasing number of first- and
      second-degree relatives diagnosed as having breast cancer for both BRCA1 (HR for 
      >/=2 vs 0 affected relatives, 1.99; 95% CI, 1.41-2.82; P<.001 for trend) and
      BRCA2 carriers (HR, 1.91; 95% CI, 1.08-3.37; P=.02 for trend). Breast cancer risk
      was higher if mutations were located outside vs within the regions bounded by
      positions c.2282-c.4071 in BRCA1 (HR, 1.46; 95% CI, 1.11-1.93; P=.007) and
      c.2831-c.6401 in BRCA2 (HR, 1.93; 95% CI, 1.36-2.74; P<.001). Conclusions and
      Relevance: These findings provide estimates of cancer risk based on BRCA1 and
      BRCA2 mutation carrier status using prospective data collection and demonstrate
      the potential importance of family history and mutation location in risk
      assessment.
FAU - Kuchenbaecker, Karoline B
AU  - Kuchenbaecker KB
AD  - Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary
      Care, University of Cambridge, Cambridge, England2Wellcome Trust Sanger
      Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, England.
FAU - Hopper, John L
AU  - Hopper JL
AD  - Centre for Epidemiology and Biostatistics, Melbourne School of Population Health,
      University of Melbourne, Melbourne, Australia.
FAU - Barnes, Daniel R
AU  - Barnes DR
AD  - Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary
      Care, University of Cambridge, Cambridge, England.
FAU - Phillips, Kelly-Anne
AU  - Phillips KA
AD  - Centre for Epidemiology and Biostatistics, Melbourne School of Population Health,
      University of Melbourne, Melbourne, Australia4Division of Cancer Medicine, Peter 
      MacCallum Cancer Centre, Melbourne, Australia5Department of Medicine, St
      Vincent's Hospital, University of Melbourne, Parkville, Australia6Sir Peter
      MacCallum Department of Oncology, University of Melbourne, Parkville, Australia.
FAU - Mooij, Thea M
AU  - Mooij TM
AD  - Department of Epidemiology, Netherlands Cancer Institute, Amsterdam, the
      Netherlands.
FAU - Roos-Blom, Marie-Jose
AU  - Roos-Blom MJ
AD  - Department of Epidemiology, Netherlands Cancer Institute, Amsterdam, the
      Netherlands8Department of Medical Informatics, Academic Medical Center,
      University of Amsterdam, Amsterdam, the Netherlands.
FAU - Jervis, Sarah
AU  - Jervis S
AD  - Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary
      Care, University of Cambridge, Cambridge, England9Mathematics Institute,
      University of Warwick, Coventry, England.
FAU - van Leeuwen, Flora E
AU  - van Leeuwen FE
AD  - Department of Epidemiology, Netherlands Cancer Institute, Amsterdam, the
      Netherlands.
FAU - Milne, Roger L
AU  - Milne RL
AD  - Centre for Epidemiology and Biostatistics, Melbourne School of Population Health,
      University of Melbourne, Melbourne, Australia10Cancer Epidemiology and
      Intelligence Division, Cancer Council Victoria, Melbourne, Australia.
FAU - Andrieu, Nadine
AU  - Andrieu N
AD  - Inserm U900, Paris, France12Institut Curie, Paris, France13Mines ParisTech,
      Fontainebleau, France14PSL Research University, Paris, France.
FAU - Goldgar, David E
AU  - Goldgar DE
AD  - Department of Dermatology, University of Utah School of Medicine, Salt Lake City,
      Utah.
FAU - Terry, Mary Beth
AU  - Terry MB
AD  - Department of Epidemiology, Columbia University, New York, New York.
FAU - Rookus, Matti A
AU  - Rookus MA
AD  - Department of Epidemiology, Netherlands Cancer Institute, Amsterdam, the
      Netherlands.
FAU - Easton, Douglas F
AU  - Easton DF
AD  - Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary
      Care, University of Cambridge, Cambridge, England.
FAU - Antoniou, Antonis C
AU  - Antoniou AC
AD  - Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary
      Care, University of Cambridge, Cambridge, England.
CN  - and the BRCA1 and BRCA2 Cohort Consortium
FAU - McGuffog, Lesley
AU  - McGuffog L
AD  - Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary
      Care, University of Cambridge, Cambridge, England.
FAU - Evans, D Gareth
AU  - Evans DG
AD  - Genomic Medicine, Manchester Academic Health Sciences Centre, Institute of Human 
      Development, Manchester University, Central Manchester University Hospitals NHS
      Foundation Trust, Manchester, England.
FAU - Barrowdale, Daniel
AU  - Barrowdale D
AD  - Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary
      Care, University of Cambridge, Cambridge, England.
FAU - Frost, Debra
AU  - Frost D
AD  - Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary
      Care, University of Cambridge, Cambridge, England.
FAU - Adlard, Julian
AU  - Adlard J
AD  - Yorkshire Regional Genetics Service, Chapel Allerton Hospital, Leeds, England.
FAU - Ong, Kai-Ren
AU  - Ong KR
AD  - West Midlands Regional Genetics Service, Birmingham Women's Hospital Healthcare
      NHS Trust, Birmingham, England.
FAU - Izatt, Louise
AU  - Izatt L
AD  - Clinical Genetics, Guy's and St Thomas' NHS Foundation Trust, London, England.
FAU - Tischkowitz, Marc
AU  - Tischkowitz M
AD  - Department of Medical Genetics and National Institute for Health Research
      Cambridge Biomedical Research Centre, University of Cambridge, Cambridge,
      England.
FAU - Eeles, Ros
AU  - Eeles R
AD  - Oncogenetics Team, Institute of Cancer Research and Royal Marsden NHS Foundation 
      Trust, Sutton, England.
FAU - Davidson, Rosemarie
AU  - Davidson R
AD  - Department of Clinical Genetics, South Glasgow University Hospitals, Glasgow,
      Scotland.
FAU - Hodgson, Shirley
AU  - Hodgson S
AD  - Department of Clinical Genetics, St George's, University of London, London,
      England.
FAU - Ellis, Steve
AU  - Ellis S
AD  - Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary
      Care, University of Cambridge, Cambridge, England.
FAU - Nogues, Catherine
AU  - Nogues C
AD  - Oncogenetique Clinique, Hopital Rene Huguenin/Institut Curie, Saint-Cloud,
      France.
FAU - Lasset, Christine
AU  - Lasset C
AD  - Unite de Prevention et d'Epidemiologie Genetique, Centre Leon Berard, Lyon,
      France.
FAU - Stoppa-Lyonnet, Dominique
AU  - Stoppa-Lyonnet D
AD  - Institut Curie, Department of Tumour Biology, Paris, France28Institut Curie,
      INSERM U830, Paris, France29Universite Paris Descartes, Sorbonne Paris Cite,
      Paris, France.
FAU - Fricker, Jean-Pierre
AU  - Fricker JP
AD  - Unite d'Oncogenetique, Centre Paul Strauss, Strasbourg, France.
FAU - Faivre, Laurence
AU  - Faivre L
AD  - Centre de Lutte Contre le Cancer Georges Francois Leclerc, Dijon, France32Centre 
      de Genetique, Hopital d'Enfants, CHU Dijon, Dijon, France.
FAU - Berthet, Pascaline
AU  - Berthet P
AD  - Centre Francois Baclesse, Caen, France.
FAU - Hooning, Maartje J
AU  - Hooning MJ
AD  - Department of Medical Oncology, Family Cancer Clinic, Erasmus MC Cancer
      Institute, Rotterdam, the Netherlands.
FAU - van der Kolk, Lizet E
AU  - van der Kolk LE
AD  - Family Cancer Clinic, Netherlands Cancer Institute, Amsterdam, the Netherlands.
FAU - Kets, Carolien M
AU  - Kets CM
AD  - Department of Human Genetics, Radboud University Medical Center, Nijmegen, the
      Netherlands.
FAU - Adank, Muriel A
AU  - Adank MA
AD  - Department of Clinical Genetics, VU University Medical Center, Amsterdam, the
      Netherlands.
FAU - John, Esther M
AU  - John EM
AD  - Department of Epidemiology, Cancer Prevention Institute of California, Fremont.
FAU - Chung, Wendy K
AU  - Chung WK
AD  - Departments of Pedicatrics and Medicine, Columbia University, New York, New York.
FAU - Andrulis, Irene L
AU  - Andrulis IL
AD  - Department of Molecular Genetics, University of Toronto, Toronto, Ontario,
      Canada41Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto,
      Ontario, Canada.
FAU - Southey, Melissa
AU  - Southey M
AD  - Genetic Epidemiology Laboratory, Department of Pathology, University of
      Melbourne, Parkville, Australia.
FAU - Daly, Mary B
AU  - Daly MB
AD  - Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia,
      Pennsylvania.
FAU - Buys, Saundra S
AU  - Buys SS
AD  - Department of Medicine, Huntsman Cancer Institute, Salt Lake City, Utah.
FAU - Osorio, Ana
AU  - Osorio A
AD  - Human Genetics Group, Spanish National Cancer Centre, Madrid, Spain46Biomedical
      Network on Rare Diseases (CIBERER), Madrid, Spain.
FAU - Engel, Christoph
AU  - Engel C
AD  - Institute for Medical Informatics, Statistics and Epidemiology, University of
      Leipzig, Leipzig, Germany48LIFE-Leipzig Research Centre for Civilization
      Diseases, University of Leipzig, Leipzig, Germany.
FAU - Kast, Karin
AU  - Kast K
AD  - Department of Gynaecology and Obstetrics, University Hospital Carl Gustav Carus, 
      Dresden, Germany50National Center for Tumor Diseases, Partner Site Dresden,
      Dresden, Germany51German Cancer Consortium, Dresden and German Cancer Research
      Center, Heidelberg, Germany.
FAU - Schmutzler, Rita K
AU  - Schmutzler RK
AD  - Center for Familial Breast and Ovarian Cancer, Center for Integrated Oncology,
      Medical Faculty, University of Cologne and University Hospital Cologne, Cologne, 
      Germany.
FAU - Caldes, Trinidad
AU  - Caldes T
AD  - Molecular Oncology Laboratory, Hospital Clinico San Carlos, Instituto de
      Investigacion Sanitaria San Carlos, Madrid, Spain.
FAU - Jakubowska, Anna
AU  - Jakubowska A
AD  - Department of Genetics and Pathology, Pomeranian Medical University, Szczecin,
      Poland.
FAU - Simard, Jacques
AU  - Simard J
AD  - Genomics Center, Centre Hospitalier Universitaire de Quebec Research Center and
      Laval University, Quebec City, Quebec, Canada.
FAU - Friedlander, Michael L
AU  - Friedlander ML
AD  - Prince of Wales Clinical School, University of New South Wales, Sydney,
      Australia57Department of Medical Oncology, Prince of Wales Hospital, Randwick,
      Australia.
FAU - McLachlan, Sue-Anne
AU  - McLachlan SA
AD  - Division of Cancer Medicine, Peter MacCallum Cancer Centre, Melbourne,
      Australia58Department of Medical Oncology, St Vincent's Hospital, Fitzroy,
      Australia.
FAU - Machackova, Eva
AU  - Machackova E
AD  - Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer
      Institute, Brno, Czech Republic.
FAU - Foretova, Lenka
AU  - Foretova L
AD  - Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer
      Institute, Brno, Czech Republic.
FAU - Tan, Yen Y
AU  - Tan YY
AD  - Department of Obstetrics and Gynecology and Comprehensive Cancer Center, Medical 
      University of Vienna, Vienna, Austria61QIMR Berghofer Medical Research Institute,
      Herston, Australia.
FAU - Singer, Christian F
AU  - Singer CF
AD  - Department of Obstetrics and Gynecology and Comprehensive Cancer Center, Medical 
      University of Vienna, Vienna, Austria.
FAU - Olah, Edith
AU  - Olah E
AD  - Department of Molecular Genetics, National Institute of Oncology, Budapest,
      Hungary.
FAU - Gerdes, Anne-Marie
AU  - Gerdes AM
AD  - Department of Clinical Genetics, Copenhagen University Hospital Rigshospital,
      Copenhagen, Denmark.
FAU - Arver, Brita
AU  - Arver B
AD  - Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden.
FAU - Olsson, Hakan
AU  - Olsson H
AD  - Department of Oncology, Lund University Hospital, Lund, Sweden.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - JAMA
JT  - JAMA
JID - 7501160
EDAT- 2017/06/21 06:00
MHDA- 2017/06/21 06:00
CRDT- 2017/06/21 06:00
AID - 2632503 [pii]
AID - 10.1001/jama.2017.7112 [doi]
PST - ppublish
SO  - JAMA. 2017 Jun 20;317(23):2402-2416. doi: 10.1001/jama.2017.7112.

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