Skip to main content
Grant Details

Grant Number: 5R01CA102740-03 Interpret this number
Primary Investigator: Goodwin, Pamela
Organization: Sinai Health System
Project Title: Prognosis in BRCA1 Associated Breast Cancer
Fiscal Year: 2007


DESCRIPTION (provided by applicant): An international population-based, prospective cohort study, conducted in Northern California, Australia and Ontario (Canada), will build upon activities of the Cooperative Familial Registry for Breast Cancer Studies (CFRBCS) to study women with BRCA1 associated or sporadic breast cancer to address the following objectives: (1) To examine the germline mutations in BRCA1 on risk of distant recurrence and death in women with newly diagnosed locoregional breast cancer (examination of the impact of mutations on distant recurrence is our primary objective). (2) To explore the frequency and prognostic importance of traditional pathologic factors and selected molecular markers (p53, HER2/neu) on distant recurrence and death in BRCA1 mutation carriers. (3) To describe the associations of treatment (systemic therapy, surgery, radiation) with outcomes (local breast events, contralateral breast events, distant recurrence, death) for BRCA1 mutation carriers and sporadic cases in order to generate hypotheses regarding treatment effects that can be tested in future randomized trials. Specifically, we will review medical records to collect detailed clinical, treatment and outcome information on women enrolled onto the prognostic study and we will perform a series of immunohistochemical assays for hormone receptors, p53 and HER2/neu. Additional information will be drawn from previously funded CFRBCS activities including detailed pathology review, results of mutation analysis, family history and demographic data. Data from these 2 sources will be incorporated into the statistical analysis which will address our 3 study objectives. Our proposed research improves upon existing research because it is population-based, prospective, involves rigorous control of clinical and pathologic prognostic factors, and includes sufficient subjects with BRCA1 associated hereditary breast cancer (100-140 women) that objectives can be addressed with adequate power (>80% power to detect hazard ratios under 2.0). It will also lead to the establishment of a well characterized cohort of 3000 women with standard clinical and pathologic data that can be used as a resource for future research into prognostic effects of mutations in BRCA2 (once testing is complete) and in other yet to be discovered breast cancer predisposition genes. Because this research is nested within the CFRBCS, the objectives can be addressed in a timely and cost effective manner.


Associations of common variants at 1p11.2 and 14q24.1 (RAD51L1) with breast cancer risk and heterogeneity by tumor subtype: findings from the Breast Cancer Association Consortium.
Authors: Figueroa J.D. , Garcia-Closas M. , Humphreys M. , Platte R. , Hopper J.L. , Southey M.C. , Apicella C. , Hammet F. , Schmidt M.K. , Broeks A. , et al. .
Source: Human molecular genetics, 2011-12-01; 20(23), p. 4693-706.
EPub date: 2011-08-18.
PMID: 21852249
Related Citations

7q21-rs6964587 and breast cancer risk: an extended case-control study by the Breast Cancer Association Consortium.
Authors: Milne R.L. , Lorenzo-Bermejo J. , Burwinkel B. , Malats N. , Arias J.I. , Zamora M.P. , Benítez J. , Humphreys M.K. , García-Closas M. , Chanock S.J. , et al. .
Source: Journal of medical genetics, 2011 Oct; 48(10), p. 698-702.
PMID: 21931171
Related Citations

Constitutional methylation of the BRCA1 promoter is specifically associated with BRCA1 mutation-associated pathology in early-onset breast cancer.
Authors: Wong E.M. , Southey M.C. , Fox S.B. , Brown M.A. , Dowty J.G. , Jenkins M.A. , Giles G.G. , Hopper J.L. , Dobrovic A. .
Source: Cancer prevention research (Philadelphia, Pa.), 2011 Jan; 4(1), p. 23-33.
EPub date: 2010-10-26.
PMID: 20978112
Related Citations

Missense variants in ATM in 26,101 breast cancer cases and 29,842 controls.
Authors: Fletcher O. , Johnson N. , dos Santos Silva I. , Orr N. , Ashworth A. , Nevanlinna H. , Heikkinen T. , Aittomäki K. , Blomqvist C. , Burwinkel B. , et al. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2010 Sep; 19(9), p. 2143-51.
PMID: 20826828
Related Citations

A BRCA1 promoter variant (rs11655505) and breast cancer risk.
Authors: Verderio P. , Pizzamiglio S. , Southey M.C. , Spurdle A.B. , Hopper J.L. , Chen X. , Beesley J. , Australian Ovarian Cancer Study Group KConFab , Schmutzler R.K. , Engel C. , et al. .
Source: Journal of medical genetics, 2010 Apr; 47(4), p. 268-70.
PMID: 20413709
Related Citations

No evidence that GATA3 rs570613 SNP modifies breast cancer risk.
Authors: Johnatty S.E. , Couch F.J. , Fredericksen Z. , Tarrell R. , Spurdle A.B. , Beesley J. , Chen X. , kConFab Investigators , AOCS Group , Swedish BRCA1 and BRCA2 Study Collaborators , et al. .
Source: Breast cancer research and treatment, 2009 Sep; 117(2), p. 371-9.
EPub date: 2008-12-11.
PMID: 19082709
Related Citations

Risk of estrogen receptor-positive and -negative breast cancer and single-nucleotide polymorphism 2q35-rs13387042.
Authors: Milne R.L. , Benítez J. , Nevanlinna H. , Heikkinen T. , Aittomäki K. , Blomqvist C. , Arias J.I. , Zamora M.P. , Burwinkel B. , Bartram C.R. , et al. .
Source: Journal of the National Cancer Institute, 2009-07-15; 101(14), p. 1012-8.
EPub date: 2009-06-30.
PMID: 19567422
Related Citations

Prediagnosis reproductive factors and all-cause mortality for women with breast cancer in the breast cancer family registry.
Authors: Phillips K.A. , Milne R.L. , West D.W. , Goodwin P.J. , Giles G.G. , Chang E.T. , Figueiredo J.C. , Friedlander M.L. , Keegan T.H. , Glendon G. , et al. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2009 Jun; 18(6), p. 1792-7.
PMID: 19505912
Related Citations

Newly discovered breast cancer susceptibility loci on 3p24 and 17q23.2.
Authors: Ahmed S. , Thomas G. , Ghoussaini M. , Healey C.S. , Humphreys M.K. , Platte R. , Morrison J. , Maranian M. , Pooley K.A. , Luben R. , et al. .
Source: Nature genetics, 2009 May; 41(5), p. 585-90.
EPub date: 2009-03-29.
PMID: 19330027
Related Citations

Psychosocial factors and survival of young women with breast cancer: a population-based prospective cohort study.
Authors: Phillips K.A. , Osborne R.H. , Giles G.G. , Dite G.S. , Apicella C. , Hopper J.L. , Milne R.L. .
Source: Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2008-10-01; 26(28), p. 4666-71.
PMID: 18824713
Related Citations

Back to Top