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Grant Details

Grant Number: 5R01CA102740-03 Interpret this number
Primary Investigator: Goodwin, Pamela
Organization: Mt Sinai Hosp-Samuel Lunenfeld Res Inst
Project Title: Prognosis in BRCA1 Associated Breast Cancer
Fiscal Year: 2007
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Abstract

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.

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Publications

7q21-rs6964587 and breast cancer risk: an extended case-control study by the Breast Cancer Association Consortium.
Authors: Milne RL, Lorenzo-Bermejo J, Burwinkel B, Malats N, Arias JI, Zamora MP, Benítez J, Humphreys MK, García-Closas M, Chanock SJ, Lissowska J, Sherman ME, Mannermaa A, Kataja V, Kosma VM, Nevanlinna H, Heikkinen T, Aittomäki K, Blomqvist C, Anton-Culver H, Ziogas A, Devilee P, van Asperen CJ, Tollenaar RA, Seynaeve C, Hall P, Czene K, Liu J, Irwanto AK, Kang D, Yoo KY, Noh DY, Couch FJ, Olson JE, Wang X, Fredericksen Z, Nordestgaard BG, Bojesen SE, Flyger H, Margolin S, Lindblom A, Fasching PA, Schulz-Wendtland R, Ekici AB, Beckmann MW, Wang-Gohrke S, Shen CY, Yu JC, Hsu HM, Wu PE, Giles GG, Severi G, Baglietto L, English DR, Cox A, Brock I, Elliott G, Reed MW, Beesley J, Chen X, Investigators K, AOCS Group, Fletcher O, Gibson L, dos Santos Silva I, Peto J, Frank B, Heil J, Meindl A, Chang-Claude J, Hein R, Vrieling A, Flesch-Janys D, Southey MC, Smith L, Apicella C, Hopper JL, Dunning AM, Pooley KA, Pharoah PD, Hamann U, Pesch B, Ko YD, GENICA Network, Easton DF, Chenevix-Trench G
Source: J Med Genet, 2011 Oct;48(10), p. 698-702.
PMID: 21931171
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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 JD, Garcia-Closas M, Humphreys M, Platte R, Hopper JL, Southey MC, Apicella C, Hammet F, Schmidt MK, Broeks A, Tollenaar RA, Van't Veer LJ, Fasching PA, Beckmann MW, Ekici AB, Strick R, Peto J, dos Santos Silva I, Fletcher O, Johnson N, Sawyer E, Tomlinson I, Kerin M, Burwinkel B, Marme F, Schneeweiss A, Sohn C, Bojesen S, Flyger H, Nordestgaard BG, Benítez J, Milne RL, Ignacio Arias J, Zamora MP, Brenner H, Müller H, Arndt V, Rahman N, Turnbull C, Seal S, Renwick A, Brauch H, Justenhoven C, Brüning T, GENICA Network, Chang-Claude J, Hein R, Wang-Gohrke S, Dörk T, Schürmann P, Bremer M, Hillemanns P, Nevanlinna H, Heikkinen T, Aittomäki K, Blomqvist C, Bogdanova N, Antonenkova N, Rogov YI, Karstens JH, Bermisheva M, Prokofieva D, Gantcev SH, Khusnutdinova E, Lindblom A, Margolin S, Chenevix-Trench G, Beesley J, Chen X, kConFab AOCS Management Group, Mannermaa A, Kosma VM, Soini Y, Kataja V, Lambrechts D, Yesilyurt BT, Chrisiaens MR, Peeters S, Radice P, Peterlongo P, Manoukian S, Barile M, Couch F, Lee AM, Diasio R, Wang X, Giles GG, Severi G, Baglietto L, Maclean C, Offit K, Robson M, Joseph V, Gaudet M, John EM, Winqvist R, Pylkäs K, Jukkola-Vuorinen A, Grip M, Andrulis I, Knight JA, Mulligan AM, O'Malley FP, Brinton LA, Sherman ME, Lissowska J, Chanock SJ, Hooning M, Martens JW, van den Ouweland AM, Collée JM, Hall P, Czene K, Cox A, Brock IW, Reed MW, Cross SS, Pharoah P, Dunning AM, Kang D, Yoo KY, Noh DY, Ahn SH, Jakubowska A, Lubinski J, Jaworska K, Durda K, Sangrajrang S, Gaborieau V, Brennan P, McKay J, Shen CY, Ding SL, Hsu HM, Yu JC, Anton-Culver H, Ziogas A, Ashworth A, Swerdlow A, Jones M, Orr N, Trentham-Dietz A, Egan K, Newcomb P, Titus-Ernstoff L, Easton D, Spurdle AB
Source: Hum Mol Genet, 2011 Dec 1;20(23), p. 4693-706.
EPub date: 2011 Aug 18.
PMID: 21852249
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Constitutional methylation of the BRCA1 promoter is specifically associated with BRCA1 mutation-associated pathology in early-onset breast cancer.
Authors: Wong EM, Southey MC, Fox SB, Brown MA, Dowty JG, Jenkins MA, Giles GG, Hopper JL, Dobrovic A
Source: Cancer Prev Res (Phila), 2011 Jan;4(1), p. 23-33.
EPub date: 2010 Oct 26.
PMID: 20978112
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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, Bartram CR, Meindl A, Schmutzler RK, Cox A, Brock I, Elliott G, Reed MW, Southey MC, Smith L, Spurdle AB, Hopper JL, Couch FJ, Olson JE, Wang X, Fredericksen Z, Schürmann P, Waltes R, Bremer M, Dörk T, Devilee P, van Asperen CJ, Tollenaar RA, Seynaeve C, Hall P, Czene K, Humphreys K, Liu J, Ahmed S, Dunning AM, Maranian M, Pharoah PD, Chenevix-Trench G, kConFab Investigators, AOCS Group, Beesley J, Bogdanova NV, Antonenkova NN, Zalutsky IV, Anton-Culver H, Ziogas A, Brauch H, Ko YD, Hamann U, GENICA Consortium, Fasching PA, Strick R, Ekici AB, Beckmann MW, Giles GG, Severi G, Baglietto L, English DR, Milne RL, Benítez J, Arias JI, Pita G, Nordestgaard BG, Bojesen SE, Flyger H, Kang D, Yoo KY, Noh DY, Mannermaa A, Kataja V, Kosma VM, García-Closas M, Chanock S, Lissowska J, Brinton LA, Chang-Claude J, Wang-Gohrke S, Broeks A, Schmidt MK, van Leeuwen FE, Van't Veer LJ, Margolin S, Lindblom A, Humphreys MK, Morrison J, Platte R, Easton DF, Peto J, Breast Cancer Association Consortium
Source: Cancer Epidemiol Biomarkers Prev, 2010 Sep;19(9), p. 2143-51.
PMID: 20826828
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A BRCA1 promoter variant (rs11655505) and breast cancer risk.
Authors: Verderio P, Pizzamiglio S, Southey MC, Spurdle AB, Hopper JL, Chen X, Beesley J, Australian Ovarian Cancer Study Group KConFab, Schmutzler RK, Engel C, Burwinkel B, Bugert P, Ficarazzi F, Manoukian S, Barile M, Wappenschmidt B, Chenevix-Trench G, Radice P, Peterlongo P
Source: J Med Genet, 2010 Apr;47(4), p. 268-70.
PMID: 20413709
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Risk of estrogen receptor-positive and -negative breast cancer and single-nucleotide polymorphism 2q35-rs13387042.
Authors: Milne RL, Benítez J, Nevanlinna H, Heikkinen T, Aittomäki K, Blomqvist C, Arias JI, Zamora MP, Burwinkel B, Bartram CR, Meindl A, Schmutzler RK, Cox A, Brock I, Elliott G, Reed MW, Southey MC, Smith L, Spurdle AB, Hopper JL, Couch FJ, Olson JE, Wang X, Fredericksen Z, Schürmann P, Bremer M, Hillemanns P, Dörk T, Devilee P, van Asperen CJ, Tollenaar RA, Seynaeve C, Hall P, Czene K, Liu J, Li Y, Ahmed S, Dunning AM, Maranian M, Pharoah PD, Chenevix-Trench G, Beesley J, kConFab Investigators, AOCS Group, Bogdanova NV, Antonenkova NN, Zalutsky IV, Anton-Culver H, Ziogas A, Brauch H, Justenhoven C, Ko YD, Haas S, Fasching PA, Strick R, Ekici AB, Beckmann MW, Giles GG, Severi G, Baglietto L, English DR, Fletcher O, Johnson N, dos Santos Silva I, Peto J, Turnbull C, Hines S, Renwick A, Rahman N, Nordestgaard BG, Bojesen SE, Flyger H, Kang D, Yoo KY, Noh DY, Mannermaa A, Kataja V, Kosma VM, García-Closas M, Chanock S, Lissowska J, Brinton LA, Chang-Claude J, Wang-Gohrke S, Shen CY, Wang HC, Yu JC, Chen ST, Bermisheva M, Nikolaeva T, Khusnutdinova E, Humphreys MK, Morrison J, Platte R, Easton DF, Breast Cancer Association Consortium
Source: J Natl Cancer Inst, 2009 Jul 15;101(14), p. 1012-8.
EPub date: 2009 Jun 30.
PMID: 19567422
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Prediagnosis reproductive factors and all-cause mortality for women with breast cancer in the breast cancer family registry.
Authors: Phillips KA, Milne RL, West DW, Goodwin PJ, Giles GG, Chang ET, Figueiredo JC, Friedlander ML, Keegan TH, Glendon G, Apicella C, O'Malley FP, Southey MC, Andrulis IL, John EM, Hopper JL
Source: Cancer Epidemiol Biomarkers Prev, 2009 Jun;18(6), p. 1792-7.
PMID: 19505912
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Newly discovered breast cancer susceptibility loci on 3p24 and 17q23.2.
Authors: Ahmed S, Thomas G, Ghoussaini M, Healey CS, Humphreys MK, Platte R, Morrison J, Maranian M, Pooley KA, Luben R, Eccles D, Evans DG, Fletcher O, Johnson N, dos Santos Silva I, Peto J, Stratton MR, Rahman N, Jacobs K, Prentice R, Anderson GL, Rajkovic A, Curb JD, Ziegler RG, Berg CD, Buys SS, McCarty CA, Feigelson HS, Calle EE, Thun MJ, Diver WR, Bojesen S, Nordestgaard BG, Flyger H, Dörk T, Schürmann P, Hillemanns P, Karstens JH, Bogdanova NV, Antonenkova NN, Zalutsky IV, Bermisheva M, Fedorova S, Khusnutdinova E, SEARCH, Kang D, Yoo KY, Noh DY, Ahn SH, Devilee P, van Asperen CJ, Tollenaar RA, Seynaeve C, Garcia-Closas M, Lissowska J, Brinton L, Peplonska B, Nevanlinna H, Heikkinen T, Aittomäki K, Blomqvist C, Hopper JL, Southey MC, Smith L, Spurdle AB, Schmidt MK, Broeks A, van Hien RR, Cornelissen S, Milne RL, Ribas G, González-Neira A, Benitez J, Schmutzler RK, Burwinkel B, Bartram CR, Meindl A, Brauch H, Justenhoven C, Hamann U, GENICA Consortium, Chang-Claude J, Hein R, Wang-Gohrke S, Lindblom A, Margolin S, Mannermaa A, Kosma VM, Kataja V, Olson JE, Wang X, Fredericksen Z, Giles GG, Severi G, Baglietto L, English DR, Hankinson SE, Cox DG, Kraft P, Vatten LJ, Hveem K, Kumle M, Sigurdson A, Doody M, Bhatti P, Alexander BH, Hooning MJ, van den Ouweland AM, Oldenburg RA, Schutte M, Hall P, Czene K, Liu J, Li Y, Cox A, Elliott G, Brock I, Reed MW, Shen CY, Yu JC, Hsu GC, Chen ST, Anton-Culver H, Ziogas A, Andrulis IL, Knight JA, kConFab, Australian Ovarian Cancer Study Group, Beesley J, Goode EL, Couch F, Chenevix-Trench G, Hoover RN, Ponder BA, Hunter DJ, Pharoah PD, Dunning AM, Chanock SJ, Easton DF
Source: Nat Genet, 2009 May;41(5), p. 585-90.
EPub date: 2009 Mar 29.
PMID: 19330027
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No evidence that GATA3 rs570613 SNP modifies breast cancer risk.
Authors: Johnatty SE, Couch FJ, Fredericksen Z, Tarrell R, Spurdle AB, Beesley J, Chen X, kConFab Investigators, AOCS Group, Swedish BRCA1 and BRCA2 Study Collaborators, Gschwantler-Kaulich D, Singer CF, Fuerhauser C, Fink-Retter A, Domchek SM, Nathanson KL, Pankratz VS, Lindor NM, Godwin AK, Caligo MA, Hopper J, Southey MC, Giles GG, Justenhoven C, Brauch H, Hamann U, Ko YD, Heikkinen T, Aaltonen K, Aittomäki K, Blomqvist C, Nevanlinna H, Hall P, Czene K, Liu J, Peock S, Cook M, Platte R, Gareth Evans D, Lalloo F, Eeles R, Pichert G, Eccles D, Davidson R, Cole T, Cook J, Douglas F, Chu C, Hodgson S, Paterson J, Hogervorst FB, Rookus MA, Seynaeve C, Wijnen J, Vreeswijk M, Ligtenberg M, van der Luijt RB, van Os TA, Gille HJ, Blok MJ, HEBON, Issacs C, Humphreys MK, McGuffog L, Healey S, Sinilnikova O, Antoniou AC, Easton DF, Chenevix-Trench G, Breast Cancer Association Consortium and Consortium of Investigators of Modifiers of BRCA1/2
Source: Breast Cancer Res Treat, 2009 Sep;117(2), p. 371-9.
EPub date: 2008 Dec 11.
PMID: 19082709
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Psychosocial factors and survival of young women with breast cancer: a population-based prospective cohort study.
Authors: Phillips KA, Osborne RH, Giles GG, Dite GS, Apicella C, Hopper JL, Milne RL
Source: J Clin Oncol, 2008 Oct 1;26(28), p. 4666-71.
PMID: 18824713
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