Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers
Karoline Kuchenbaecker,Karoline Kuchenbaecker,John L. Hopper,Daniel R. Barnes,Kelly-Anne Phillips,T.M. Mooij,Marie-José Roos-Blom,Marie-José Roos-Blom,Sarah Jervis,Sarah Jervis,Flora E. van Leeuwen,Roger L. Milne,Roger L. Milne,Nadine Andrieu,David E. Goldgar,Mary Beth Terry,Matti A. Rookus,Douglas F. Easton,Antonis C. Antoniou,Lesley McGuffog,D. Gareth Evans,Daniel Barrowdale,Debra Frost,Julian Adlard,Kai-ren Ong,Louise Izatt,Marc Tischkowitz,Ros Eeles,Rosemarie Davidson,Shirley Hodgson,Steve Ellis,Catherine Noguès,Christine Lasset,Dominique Stoppa-Lyonnet,Dominique Stoppa-Lyonnet,Jean-Pierre Fricker,Laurence Faivre,Pascaline Berthet,Maartje J. Hooning,Lizet E. van der Kolk,Carolien M. Kets,Muriel A. Adank,Esther M. John,Wendy K. Chung,Irene L. Andrulis,Irene L. Andrulis,Melissa C. Southey,Mary B. Daly,Saundra S. Buys,Ana Osorio,Christoph Engel,Karin Kast,Rita K. Schmutzler,Trinidad Caldés,Anna Jakubowska,Jacques Simard,Michael Friedlander,Sue-Anne McLachlan,Sue-Anne McLachlan,Eva Machackova,Lenka Foretova,Yen Y. Tan,Yen Y. Tan,Christian F. Singer,Edith Olah,Anne-Marie Gerdes,Brita Arver,Håkan Olsson +67 more
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TLDR
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, a large cohort study recruited in 1997-2011 provides estimates of cancer risk based on BRCA1 and BRCa2 mutation carrier status.Abstract:
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.read more
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References
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Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: a combined analysis of 22 studies
Antonis C. Antoniou,Paul D.P. Pharoah,Steven A. Narod,Harvey A. Risch,Jorunn E. Eyfjord,John L. Hopper,Niklas Loman,Håkan Olsson,Oskar T. Johannsson,Åke Borg,Barbara Pasini,Paolo Radice,Siranoush Manoukian,Diana Eccles,Nelson L.S. Tang,E. Olah,Hoda Anton-Culver,Ellen Warner,Jan Lubinski,Jacek Gronwald,Bohdan Górski,Hrafn Tulinius,Steinunn Thorlacius,Hannaleena Eerola,Heli Nevanlinna,Kirsi Syrjäkoski,Olli Kallioniemi,Deborah J. Thompson,Christopher H. Evans,Julian Peto,Julian Peto,Fiona Lalloo,D G R Evans,Douglas F. Easton +33 more
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Meta-analysis of BRCA1 and BRCA2 penetrance
Sining Chen,Giovanni Parmigiani +1 more
TL;DR: A set of risk estimates for BRCa1 and BRCA2 mutation carriers that can be used by counselors and clinicians who are interested in advising patients based on a comprehensive set of studies rather than one specific study are provided.
Journal ArticleDOI
Cancer Risks for BRCA1 and BRCA2 Mutation Carriers: Results From Prospective Analysis of EMBRACE
Nasim Mavaddat,Susan Peock,Debra Frost,Steve Ellis,Radka Platte,Elena Fineberg,D. Gareth Evans,Louise Izatt,Rosalind A. Eeles,Julian Adlard,Rosemarie Davidson,Diana Eccles,Trevor Cole,Jackie Cook,Carole Brewer,Marc Tischkowitz,Fiona Douglas,Shirley Hodgson,Lisa Walker,Mary Porteous,Patrick J. Morrison,Lucy Side,M. John Kennedy,C. E. Houghton,Alan Donaldson,Mark T. Rogers,Huw Dorkins,Zosia Miedzybrodzka,Helen Gregory,Jacqueline Eason,Julian Barwell,Emma McCann,Alex Murray,Antonis C. Antoniou,Douglas F. Easton +34 more
TL;DR: Prospective risk estimates for breast cancer, ovarian cancer, and contralateral breast cancer in a prospective series of mutation carriers confirm findings from retrospective studies that common breast cancer susceptibility alleles in combination are predictive of breast cancer risk for BRCA2 carriers.
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