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Grant Details

Grant Number: 5R01CA089608-05 Interpret this number
Primary Investigator: Bondy, Melissa
Organization: University Of Tx Md Anderson Can Ctr
Project Title: Determinants of Breast Cancer Survival
Fiscal Year: 2006
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Abstract

We propose a molecular epidemiologic cohort study of all newly diagnosed Stage IIA and IIB breast cancer patients who registered at The University of Texas M.D. Anderson Cancer Center (MDACC) between January 1, 1985 and December 31, 1999, and were residents of the state of Texas (N=2,875). This cohort is characterized by extensive long-term follow-up, and equal access to "best of care" practices. It offers us the opportunity to test hypotheses regarding the role of host genetic (i.e., such as gene polymorphisms in drug and radiation sensitivity, family history and ethnicity) and exposure factors (i.e., smoking, reproductive events, BMI, HRT, co-morbid conditions) in relation to tumor phenotype, as independent and interactive determinants of risk of recurrence, distant metastasis, contralateral breast cancer, second malignancies, and/or disease-free survival. In this population, we will examine a series of promising candidate host genetic markers and suspected environmental and lifestyle factors for their added value in clinical decision making when compared or combined with standard histopathological prognostic markers (e.g., lymph node status, tumor size, histological grade). In order to address our study hypotheses, we propose the following 4 specific aims: 1) To compile a comprehensive database of epidemiologic risk factors and clinical data (including treatment, pathology, and long-term follow-up) on all breast cancer patients seen exclusively at MDACC for Stage II disease. 2) To evaluate baseline epidemiologic profiles as independent and inter-related determinants of risk of recurrence, distant metastasis, contralateral breast cancer, new primary malignancies, and disease-free survival. These profiles will include comprehensive information on the use of tobacco, reproductive factors including ovarectomy and the use of HRT, body mass index (BMI), family history of cancer, age and ethnicity in relation to standard histopathology markers. 3) We will evaluate the interaction between these epidemiological factors and a) host and b) tumor molecular markers that show a relationship with disease prognosis and patient events. Specifically, in our sample set we will evaluate: the tumor specific expression of HER2-neu, Ki-67, ER, PR and p53, using standardized immunohistochemical analysis, as informative markers of tumor phenotype and patient performance. Inherited variability in genes that modulate host sensitivity to therapeutic agents, including the glutathione sulfotransferase (GSTpi, GSTM1, GSTT1); enzymes important in defending against chemical injury by catalyzing conjugation of reactive electrophilic molecules with glutathione, and an allele variant in the multi-drug resistance gene MDR-1 whose products, P- glycoprotein, is strongly linked with chemotherapeutic resistance. Our fourth aim is to construct statistical models to determine which marker or combination of markers and host factors (genetic and lifestyle) are better predictors of patient performance than the commonly used histopathologic methods.

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Publications

Impact of acculturation on breast cancer treatment and survivorship care among Mexican American patients in Texas.
Authors: Advani P. , Bondy M. , Thompson P.A. , Martínez M.E. , Nodora J.N. , Vernon S.W. , Diamond P. , Burnett J. , Brewster A.M. .
Source: Journal of cancer survivorship : research and practice, 2018 10; 12(5), p. 659-668.
EPub date: 2018-07-25.
PMID: 30043339
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Association between germline single nucleotide polymorphisms in the PI3K-AKT-mTOR pathway, obesity, and breast cancer disease-free survival.
Authors: Pande M. , Bondy M.L. , Do K.A. , Sahin A.A. , Ying J. , Mills G.B. , Thompson P.A. , Brewster A.M. .
Source: Breast cancer research and treatment, 2014 Sep; 147(2), p. 381-7.
EPub date: 2014-08-10.
PMID: 25108739
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Loss of LRIG1 locus increases risk of early and late relapse of stage I/II breast cancer.
Authors: Thompson P.A. , Ljuslinder I. , Tsavachidis S. , Brewster A. , Sahin A. , Hedman H. , Henriksson R. , Bondy M.L. , Melin B.S. .
Source: Cancer research, 2014-06-01; 74(11), p. 2928-35.
PMID: 24879564
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Genomic copy number imbalances associated with bone and non-bone metastasis of early-stage breast cancer.
Authors: Liu Y. , Zhou R. , Baumbusch L.O. , Tsavachidis S. , Brewster A.M. , Do K.A. , Sahin A. , Hortobagyi G.N. , Taube J.H. , Mani S.A. , et al. .
Source: Breast cancer research and treatment, 2014 Jan; 143(1), p. 189-201.
EPub date: 2013-12-04.
PMID: 24305980
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Prognostic value of single nucleotide polymorphisms of candidate genes associated with inflammation in early stage breast cancer.
Authors: Murray J.L. , Thompson P. , Yoo S.Y. , Do K.A. , Pande M. , Zhou R. , Liu Y. , Sahin A.A. , Bondy M.L. , Brewster A.M. .
Source: Breast cancer research and treatment, 2013 Apr; 138(3), p. 917-24.
EPub date: 2013-03-26.
PMID: 23529385
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Genetic variants in the vitamin D pathway and breast cancer disease-free survival.
Authors: Pande M. , Thompson P.A. , Do K.A. , Sahin A.A. , Amos C.I. , Frazier M.L. , Bondy M.L. , Brewster A.M. .
Source: Carcinogenesis, 2013 Mar; 34(3), p. 587-94.
EPub date: 2012-11-24.
PMID: 23180655
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The relationship between eight GWAS-identified single-nucleotide polymorphisms and primary breast cancer outcomes.
Authors: Bayraktar S. , Thompson P.A. , Yoo S.Y. , Do K.A. , Sahin A.A. , Arun B.K. , Bondy M.L. , Brewster A.M. .
Source: The oncologist, 2013; 18(5), p. 493-500.
EPub date: 2013-05-01.
PMID: 23635555
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Factors that influence mammography use and breast cancer detection among Mexican-American and African-American women.
Authors: Garcia R.Z. , Carvajal S.C. , Wilkinson A.V. , Thompson P.A. , Nodora J.N. , Komenaka I.K. , Brewster A. , Cruz G.I. , Wertheim B.C. , Bondy M.L. , et al. .
Source: Cancer causes & control : CCC, 2012 Jan; 23(1), p. 165-73.
EPub date: 2011-11-13.
PMID: 22080276
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A review of body size and breast cancer risk in Hispanic and African American women.
Authors: Sexton K.R. , Franzini L. , Day R.S. , Brewster A. , Vernon S.W. , Bondy M.L. .
Source: Cancer, 2011-12-01; 117(23), p. 5271-81.
EPub date: 2011-05-19.
PMID: 21598244
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Copy number imbalances between screen- and symptom-detected breast cancers and impact on disease-free survival.
Authors: Brewster A.M. , Thompson P. , Sahin A.A. , Do K. , Edgerton M. , Murray J.L. , Tsavachidis S. , Zhou R. , Liu Y. , Zhang L. , et al. .
Source: Cancer prevention research (Philadelphia, Pa.), 2011 Oct; 4(10), p. 1609-16.
EPub date: 2011-07-27.
PMID: 21795423
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Expression and relevance of TRPS-1: a new GATA transcription factor in breast cancer.
Authors: Chen J.Q. , Bao Y. , Litton J. , Xiao L. , Zhang H.Z. , Warneke C.L. , Wu Y. , Shen X. , Wu S. , Katz R.L. , et al. .
Source: Hormones & cancer, 2011 Apr; 2(2), p. 132-43.
PMID: 21761336
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Selective genomic copy number imbalances and probability of recurrence in early-stage breast cancer.
Authors: Thompson P.A. , Brewster A.M. , Kim-Anh D. , Baladandayuthapani V. , Broom B.M. , Edgerton M.E. , Hahn K.M. , Murray J.L. , Sahin A. , Tsavachidis S. , et al. .
Source: PloS one, 2011; 6(8), p. e23543.
EPub date: 2011-08-12.
PMID: 21858162
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Quantitative immunohistochemical analysis and prognostic significance of TRPS-1, a new GATA transcription factor family member, in breast cancer.
Authors: Chen J.Q. , Litton J. , Xiao L. , Zhang H.Z. , Warneke C.L. , Wu Y. , Shen X. , Wu S. , Sahin A. , Katz R. , et al. .
Source: Hormones & cancer, 2010 Feb; 1(1), p. 21-33.
EPub date: 2010-02-13.
PMID: 21761348
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Premenopausal breast cancer: estrogen receptor status and insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-3 (IGFBP-3), and leptin.
Authors: Eng-Wong J. , Perkins S.N. , Bondy M. , Li D. , Eva Singletary S. , Núñez N. , Hursting S. , Chang S. .
Source: The breast journal, 2009 Jul-Aug; 15(4), p. 426-8.
PMID: 19601950
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High quality copy number and genotype data from FFPE samples using Molecular Inversion Probe (MIP) microarrays.
Authors: Wang Y. , Carlton V.E. , Karlin-Neumann G. , Sapolsky R. , Zhang L. , Moorhead M. , Wang Z.C. , Richardson A.L. , Warren R. , Walther A. , et al. .
Source: BMC medical genomics, 2009-02-19; 2, p. 8.
EPub date: 2009-02-19.
PMID: 19228381
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Relationship between obesity and pathologic response to neoadjuvant chemotherapy among women with operable breast cancer.
Authors: Litton J.K. , Gonzalez-Angulo A.M. , Warneke C.L. , Buzdar A.U. , Kau S.W. , Bondy M. , Mahabir S. , Hortobagyi G.N. , Brewster A.M. .
Source: Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2008-09-01; 26(25), p. 4072-7.
PMID: 18757321
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Residual risk of breast cancer recurrence 5 years after adjuvant therapy.
Authors: Brewster A.M. , Hortobagyi G.N. , Broglio K.R. , Kau S.W. , Santa-Maria C.A. , Arun B. , Buzdar A.U. , Booser D.J. , Valero V. , Bondy M. , et al. .
Source: Journal of the National Cancer Institute, 2008-08-20; 100(16), p. 1179-83.
EPub date: 2008-08-11.
PMID: 18695137
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Relationship between epidemiologic risk factors and breast cancer recurrence.
Authors: Brewster A.M. , Do K.A. , Thompson P.A. , Hahn K.M. , Sahin A.A. , Cao Y. , Stewart M.M. , Murray J.L. , Hortobagyi G.N. , Bondy M.L. .
Source: Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2007-10-01; 25(28), p. 4438-44.
EPub date: 2007-09-04.
PMID: 17785707
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Reduced DNA repair of benzo[a]pyrene diol epoxide-induced adducts and common XPD polymorphisms in breast cancer patients.
Authors: Shi Q. , Wang L.E. , Bondy M.L. , Brewster A. , Singletary S.E. , Wei Q. .
Source: Carcinogenesis, 2004 Sep; 25(9), p. 1695-700.
EPub date: 2004-04-16.
PMID: 15090466
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