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Grant Details

Grant Number: 5R01CA132879-05 Interpret this number
Primary Investigator: Hartmann, Lynn
Organization: Mayo Clinic Rochester
Project Title: Risk Prediction for Breast Cancer: a Tissue-Based Strategy
Fiscal Year: 2012
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Abstract

DESCRIPTION (provided by applicant): Optimal early detection and prevention strategies for breast cancer depend on our ability to accurately identify individuals with significantly increased risk for this disease. Unfortunately the ability of the medical community to predict risk of breast cancer accurately for individual women remains limited. Risk assessment for other cancers is enhanced significantly when the tissue at risk can be examined for premalignant features (models include cervix, colon, esophagus, etc). This suggests that a tissue-based strategy could enhance risk prediction for breast cancer. Of note, the diagnostic categories seen in breast biopsies with benign findings (so-called benign breast disease [BBD]) - non-proliferative, proliferative without atypia and atypical hyperplasia - are accepted by many to form a continuum in the progression toward breast cancer. This histological assessment can serve as a base to which other markers of risk can be added for the construction of tissue based risk prediction strategies for breast cancer. To this end, we have assembled a large cohort of women with BBD identified at Mayo Clinic. Over the period of this proposed grant, the cohort will be expanded to include ~ 13,000 women who had biopsies 1967-2001 and who will have developed an expected ~ 1200 breast cancers. For the women in this Mayo BBD Cohort, we have collected extensive histologic features along with clinical and epidemiologic risk factors. Original benign tissue will be available for all women included, and these BBD tissue blocks will be used in the study of select biomarkers. In our work to date, we have shown that robust discriminatory features are detectable within the benign tissue. These include the overall diagnostic category of BBD, the extent of the proliferative process (e.g. number of foci), the extent of involution of background terminal duct lobular units and the expression of COX-2, the first biomarker tested. This further motivates our hypothesis that a comprehensive model that incorporates histologic and molecular features from benign breast tissue can enhance the precision of breast cancer risk prediction. The proposed work encompasses three aims that will be performed in a nested case-control series within the cohort: 1) test the calibration and discriminatory accuracy of the three available risk prediction models that incorporate BBDrelated data (Gail, Tyrer-Cuzick, Colditz-Rosner); 2) build a tissue-based risk prediction model that incorporates histologic and molecular features, along with clinical and epidemiologic risk factors and 3) validate the best model from aim 2 in an independent set of cases and controls from Mayo and two external validation sets from BBD cohorts at Vanderbilt and Henry Ford Hospital. With the assessment of the performance of risk prediction tools in women with BBD, and the construction and validation of a tissue-based risk prediction model, we aim to improve the accuracy of breast cancer risk assessment. PUBLIC HEALTH RELEVANCE: Accurate prediction of who is at increased risk for breast cancer is essential to identify those women who would benefit most from heightened surveillance and risk reduction strategies. Women who have had breast biopsies with benign findings (approximately 1 million US women/year) are known to be at increased risk for a later breast cancer. In their tissue we have found strong correlates of risk of a later breast cancer. We will combine tissue-based histologic and biomarker information, with standard risk factor data, from a large cohort of women with benign breast biopsies to craft a comprehensive risk prediction model for breast cancer.

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Publications

Sclerosing adenosis and risk of breast cancer.
Authors: Visscher DW, Nassar A, Degnim AC, Frost MH, Vierkant RA, Frank RD, Tarabishy Y, Radisky DC, Hartmann LC
Source: Breast Cancer Res Treat, 2014 Feb;144(1), p. 205-12.
EPub date: 2014 Feb 8.
PMID: 24510013
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Benign breast disease and the risk of subsequent breast cancer in African American women.
Authors: Cote ML, Ruterbusch JJ, Alosh B, Bandyopadhyay S, Kim E, Albashiti B, Sharaf Aldeen B, Radisky DC, Frost MH, Visscher DW, Hartmann LC, Nassar WH, Ali-Femhi R
Source: Cancer Prev Res (Phila), 2012 Dec;5(12), p. 1375-80.
EPub date: 2012 Oct 19.
PMID: 23087047
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Involvement of hnRNP A1 in the matrix metalloprotease-3-dependent regulation of Rac1 pre-mRNA splicing.
Authors: Pelisch F, Khauv D, Risso G, Stallings-Mann M, Blaustein M, Quadrana L, Radisky DC, Srebrow A
Source: J Cell Biochem, 2012 Jul;113(7), p. 2319-29.
PMID: 22345078
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Atypical apocrine adenosis of the breast: long-term follow-up in 37 patients.
Authors: Fuehrer N, Hartmann L, Degnim A, Allers T, Vierkant R, Frost M, Visscher D
Source: Arch Pathol Lab Med, 2012 Feb;136(2), p. 179-82.
PMID: 22288965
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p16(INK4a) expression and breast cancer risk in women with atypical hyperplasia.
Authors: Radisky DC, Santisteban M, Berman HK, Gauthier ML, Frost MH, Reynolds CA, Vierkant RA, Pankratz VS, Visscher DW, Tlsty TD, Hartmann LC
Source: Cancer Prev Res (Phila), 2011 Dec;4(12), p. 1953-60.
EPub date: 2011 Sep 15.
PMID: 21920875
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Histologic findings in normal breast tissues: comparison to reduction mammaplasty and benign breast disease tissues.
Authors: Degnim AC, Visscher DW, Hoskin TL, Frost MH, Vierkant RA, Vachon CM, Shane Pankratz V, Radisky DC, Hartmann LC
Source: Breast Cancer Res Treat, 2012 May;133(1), p. 169-77.
EPub date: 2011 Sep 1.
PMID: 21881938
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Tissue composition of mammographically dense and non-dense breast tissue.
Authors: Ghosh K, Brandt KR, Reynolds C, Scott CG, Pankratz VS, Riehle DL, Lingle WL, Odogwu T, Radisky DC, Visscher DW, Ingle JN, Hartmann LC, Vachon CM
Source: Breast Cancer Res Treat, 2012 Jan;131(1), p. 267-75.
EPub date: 2011 Aug 30.
PMID: 21877142
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Estrogen receptor expression in atypical hyperplasia: lack of association with breast cancer.
Authors: Barr FE, Degnim AC, Hartmann LC, Radisky DC, Boughey JC, Anderson SS, Vierkant RA, Frost MH, Visscher DW, Reynolds C
Source: Cancer Prev Res (Phila), 2011 Mar;4(3), p. 435-44.
EPub date: 2011 Jan 5.
PMID: 21209395
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Microenvironmental influences that drive progression from benign breast disease to invasive breast cancer.
Authors: Cichon MA, Degnim AC, Visscher DW, Radisky DC
Source: J Mammary Gland Biol Neoplasia, 2010 Dec;15(4), p. 389-97.
EPub date: 2010 Dec 16.
PMID: 21161341
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Independent association of lobular involution and mammographic breast density with breast cancer risk.
Authors: Ghosh K, Vachon CM, Pankratz VS, Vierkant RA, Anderson SS, Brandt KR, Visscher DW, Reynolds C, Frost MH, Hartmann LC
Source: J Natl Cancer Inst, 2010 Nov 17;102(22), p. 1716-23.
EPub date: 2010 Oct 29.
PMID: 21037116
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Evaluation of the Tyrer-Cuzick (International Breast Cancer Intervention Study) model for breast cancer risk prediction in women with atypical hyperplasia.
Authors: Boughey JC, Hartmann LC, Anderson SS, Degnim AC, Vierkant RA, Reynolds CA, Frost MH, Pankratz VS
Source: J Clin Oncol, 2010 Aug 1;28(22), p. 3591-6.
EPub date: 2010 Jul 6.
PMID: 20606088
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Pseudoangiomatous stromal hyperplasia and breast cancer risk.
Authors: Degnim AC, Frost MH, Radisky DC, Anderson SS, Vierkant RA, Boughey JC, Pankratz VS, Ghosh K, Hartmann LC, Visscher DW
Source: Ann Surg Oncol, 2010 Dec;17(12), p. 3269-77.
EPub date: 2010 Jun 22.
PMID: 20567920
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Matrix metalloproteinase-induced epithelial-mesenchymal transition in breast cancer.
Authors: Radisky ES, Radisky DC
Source: J Mammary Gland Biol Neoplasia, 2010 Jun;15(2), p. 201-12.
EPub date: 2010 May 5.
PMID: 20440544
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Association between mammographic density and age-related lobular involution of the breast.
Authors: Ghosh K, Hartmann LC, Reynolds C, Visscher DW, Brandt KR, Vierkant RA, Scott CG, Radisky DC, Sellers TA, Pankratz VS, Vachon CM
Source: J Clin Oncol, 2010 May 1;28(13), p. 2207-12.
EPub date: 2010 Mar 29.
PMID: 20351335
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Novel breast tissue feature strongly associated with risk of breast cancer.
Authors: McKian KP, Reynolds CA, Visscher DW, Nassar A, Radisky DC, Vierkant RA, Degnim AC, Boughey JC, Ghosh K, Anderson SS, Minot D, Caudill JL, Vachon CM, Frost MH, Pankratz VS, Hartmann LC
Source: J Clin Oncol, 2009 Dec 10;27(35), p. 5893-8.
EPub date: 2009 Oct 5.
PMID: 19805686
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Ki67: a time-varying biomarker of risk of breast cancer in atypical hyperplasia.
Authors: Santisteban M, Reynolds C, Barr Fritcher EG, Frost MH, Vierkant RA, Anderson SS, Degnim AC, Visscher DW, Pankratz VS, Hartmann LC
Source: Breast Cancer Res Treat, 2010 Jun;121(2), p. 431-7.
EPub date: 2009 Sep 23.
PMID: 19774459
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Mammary involution and breast cancer risk: transgenic models and clinical studies.
Authors: Radisky DC, Hartmann LC
Source: J Mammary Gland Biol Neoplasia, 2009 Jun;14(2), p. 181-91.
EPub date: 2009 Apr 30.
PMID: 19404726
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Lobular involution: localized phenomenon or field effect?
Authors: Vierkant RA, Hartmann LC, Pankratz VS, Anderson SS, Radisky D, Frost MH, Vachon CM, Ghosh K, Distad TJ, Degnim AC, Reynolds CA
Source: Breast Cancer Res Treat, 2009 Sep;117(1), p. 193-6.
EPub date: 2008 Jul 1.
PMID: 18592369
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