Skip to main content
Grant Details

Grant Number: 5R01CA207365-04 Interpret this number
Primary Investigator: Rebbeck, Timothy
Organization: Dana-Farber Cancer Inst
Project Title: Precision Assessment and Delivery of Cancer Risks in Brca 1/2 Mutation Cancers
Fiscal Year: 2020


Project Summary In current risk assessment and counseling practices, all women who test positive for a deleterious BRCA1/2 mutation are quoted the same general range of ovarian cancer risk and are given the same recommendation regarding utilization of risk reducing salpingo- oophorectomy (RRSO) and other preventive measures. We have recently published a model that reports substantial and clinically relevant differences in risk depending on the specific mutation a woman has inherited. In particular, we have recently shown that specific mutations confer an increased risk or earlier age of onset for breast or ovarian cancer compared with the generic risk estimates made for any BRCA1/2 mutation. In addition, risk estimates that consider previous exposure to important risk factors (e.g., reproductive history, oral contraceptive use, or preventive surgery use) may have a large impact on cancer risk estimates in this population. More precise risk information could be critical for optimal decision-making for women who are considering cancer prevention strategies. Based on these initial observations, we propose to develop precision absolute risk models that incorporate information about mutation risk group, to apply in vitro methods to identify new clinically relevant BRCA1/2 mutations and validate their capacity to cause disease, and to gain a better understanding of how personal values affect how individual women interpret and act on risk estimates, for use in a future decision aid intervention. Thus, this proposal will develop a “precision prevention” approach to BRCA1/2-associated cancer risk to lower the chances a woman will die from ovarian cancer, and will have immediate translational impact for women with BRCA1/2 mutations.


Optimal sampling for positive only electronic health record data.
Authors: Lee S.H. , Ma Y. , Wei Y. , Chen J. .
Source: Biometrics, 2023 Dec; 79(4), p. 2974-2986.
EPub date: 2023-01-28.
PMID: 36632649
Related Citations

Reply to V. Fallet et al.
Authors: Li S. , Silvestri V. , Rebbeck T.R. , Neuhausen S.L. , Hopper J.L. , Nielsen H.R. , Ottini L. , Antoniou A.C. .
Source: Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2022-08-01; 40(22), p. 2509-2510.
EPub date: 2022-05-12.
PMID: 35549306
Related Citations

The tumor mutational landscape of BRCA2-deficient primary and metastatic prostate cancer.
Authors: Kensler K.H. , Baichoo S. , Pathania S. , Rebbeck T.R. .
Source: NPJ precision oncology, 2022-06-17; 6(1), p. 39.
EPub date: 2022-06-17.
PMID: 35715489
Related Citations

Cancer in sub-Saharan Africa: a Lancet Oncology Commission.
Authors: Ngwa W. , Addai B.W. , Adewole I. , Ainsworth V. , Alaro J. , Alatise O.I. , Ali Z. , Anderson B.O. , Anorlu R. , Avery S. , et al. .
Source: The Lancet. Oncology, 2022 Jun; 23(6), p. e251-e312.
EPub date: 2022-05-09.
PMID: 35550267
Related Citations

Cancer Risks Associated With BRCA1 and BRCA2 Pathogenic Variants.
Authors: Li S. , Silvestri V. , Leslie G. , Rebbeck T.R. , Neuhausen S.L. , Hopper J.L. , Nielsen H.R. , Lee A. , Yang X. , McGuffog L. , et al. .
Source: Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2022-05-10; 40(14), p. 1529-1541.
EPub date: 2022-01-25.
PMID: 35077220
Related Citations

Therapeutic implications of germline vulnerabilities in DNA repair for precision oncology.
Authors: Shah S.M. , Demidova E.V. , Lesh R.W. , Hall M.J. , Daly M.B. , Meyer J.E. , Edelman M.J. , Arora S. .
Source: Cancer treatment reviews, 2022 Mar; 104, p. 102337.
EPub date: 2022-01-05.
PMID: 35051883
Related Citations

Risk factors for an advanced breast cancer diagnosis within 2 years of a negative mammogram.
Authors: McCarthy A.M. , Ehsan S. , Appel S. , Welch M. , He W. , Bahl M. , Chen J. , Lehman C.D. , Armstrong K. .
Source: Cancer, 2021-09-15; 127(18), p. 3334-3342.
EPub date: 2021-06-01.
PMID: 34061353
Related Citations

A pedigree-based prediction model identifies carriers of deleterious de novo mutations in families with Li-Fraumeni syndrome.
Authors: Gao F. , Pan X. , Dodd-Eaton E.B. , Recio C.V. , Montierth M.D. , Bojadzieva J. , Mai P.L. , Zelley K. , Johnson V.E. , Braun D. , et al. .
Source: Genome research, 2020 Aug; 30(8), p. 1170-1180.
EPub date: 2020-08-18.
PMID: 32817165
Related Citations

Phenotyping issues for exploring electronic health records to design clinical trials.
Authors: Schnall J. , Zhang L. , Chen J. .
Source: Clinical trials (London, England), 2020 Aug; 17(4), p. 402-404.
EPub date: 2020-06-10.
PMID: 32522027
Related Citations

Legacy Genetic Testing Results for Cancer Susceptibility: How Common are Conflicting Classifications in a Large Variant Dataset from Multiple Practices?
Authors: Yin K. , Liu Y. , Lamichhane B. , Sandbach J.F. , Patel G. , Compagnoni G. , Kanak R.H. , Rosen B. , Ondrula D.P. , Smith L. , et al. .
Source: Annals of surgical oncology, 2020 Jul; 27(7), p. 2212-2220.
EPub date: 2020-04-27.
PMID: 32342295
Related Citations

Novel two-phase sampling designs for studying binary outcomes.
Authors: Wang L. , Williams M.L. , Chen Y. , Chen J. .
Source: Biometrics, 2020 Mar; 76(1), p. 210-223.
EPub date: 2019-11-14.
PMID: 31449330
Related Citations

Precision prophylaxis: Identifying the optimal timing for risk-reducing salpingo-oophorectomy based on type of BRCA1 and BRCA2 cluster region mutations.
Authors: Solsky I. , Chen J. , Rebbeck T.R. .
Source: Gynecologic oncology, 2020 Feb; 156(2), p. 363-376.
EPub date: 2020-01-07.
PMID: 31918993
Related Citations

BRCA1 and BRCA2 pathogenic sequence variants in women of African origin or ancestry.
Authors: Friebel T.M. , Andrulis I.L. , Balmaña J. , Blanco A.M. , Couch F.J. , Daly M.B. , Domchek S.M. , Easton D.F. , Foulkes W.D. , Ganz P.A. , et al. .
Source: Human mutation, 2019 Oct; 40(10), p. 1781-1796.
EPub date: 2019-07-03.
PMID: 31112363
Related Citations

Back to Top