Grant Number:	5R01CA070923-04 Interpret this number
Primary Investigator:	Worsham, Maria
Organization:	Henry Ford Health System
Project Title:	Benign Breast Disease-Molecular Differentiation of Risk
Fiscal Year:	1999

DESCRIPTION: (Adapted from Investigator's Abstract) Although the risk of breast cancer for women in the U.S. is approximately 1 in 9, identification of risk factors and translation of that knowledge into strategies for prevention have been inhibited by poor understanding of disease pathogenesis. A few benign breast proliferations are associated with higher risk of breast cancer but definition of a preneoplastic morphologic continuum is lacking. The investigators propose to study 5353 eligible women, derived from a large multi-ethnic population, diagnosed by biopsy with benign breast disease between 1981-1991, followed from 5-15 years, and yielding an estimated 248 women who will have developed invasive breast cancer. The overall aims are to 1) ascertain the incidence and time span of breast cancer development in this cohort, 2) to estimate the frequency of selected genetic alterations in both benign breast disease (BBD) and invasive cancers from the same individuals in a subset of the cohort and 3) using a nested case-control approach, to evaluate risk factors for breast cancer among women with BBD, including specific histological characteristics, molecular markers, family history of breast cancer, and reproductive history. The purpose of the study is to evaluate the importance of biomarkers for risk for breast cancer development and determination of their contribution to definition of a genetic sequence in breast carcinogenesis. Assessment of genetic alterations will employ florescent in situ hybridization and the polymerase chain reaction (PCR). The PI will identify chromosomal aneuploidy, selective with respect to individual chromosomes and as a measure of DNA ploidy, and HER-2/neu amplification patterns in BBD and invasive cancer. The PI will identify p53 mutations by single strand conformation analysis (SSCP), determine clonality using the PCR nested primer approach for the PGK locus (on Xq arm), and assess loss of heterozygosity (LOH) for intragenic markers of the BRCA1 (17q21) and E-cadherin (16q22) genes. When LOH is observed, analysis of the genes using SSCP will attempt to identify the putative mutations. Lack of a constitutional BRCA1 mutation will rule out one form of inherited breast cancer, allowing subtyping of the remaining tumors by histopathological and genetic profiles, and time frame of cancer development. This study should help establish a genetic and morphologic continuum from BBD to breast cancer and provide a firmer basis for interpretation of the roles of known risk factors, with the eventual objective of permitting targeted testing of preventive strategies and therapeutic regimens.




Delineating an epigenetic continuum for initiation, transformation and progression to breast cancer.
Authors: Chen K.M. , Stephen J.K. , Raju U. , Worsham M.J. .
Source: Cancers, 2011 Jun; 3(2), p. 1580-92.
PMID: 21776373
Related Citations

Risk factors for breast cancer from benign breast disease in a diverse population.
Authors: Worsham M.J. , Raju U. , Lu M. , Kapke A. , Botttrell A. , Cheng J. , Shah V. , Savera A. , Wolman S.R. .
Source: Breast Cancer Research And Treatment, 2009 Nov; 118(1), p. 1-7.
EPub date: 2008-10-04 00:00:00.0.
PMID: 18836828
Related Citations

Benign breast disease heterogeneity: association with histopathology, age, and ethnicity.
Authors: Cheng J. , Qiu S. , Raju U. , Wolman S.R. , Worsham M.J. .
Source: Breast Cancer Research And Treatment, 2008 Sep; 111(2), p. 289-96.
EPub date: 2007-10-05 00:00:00.0.
PMID: 17917807
Related Citations

Breast cancer incidence in a cohort of women with benign breast disease from a multiethnic, primary health care population.
Authors: Worsham M.J. , Abrams J. , Raju U. , Kapke A. , Lu M. , Cheng J. , Mott D. , Wolman S.R. .
Source: The Breast Journal, 2007 Mar-Apr; 13(2), p. 115-21.
PMID: 17319851
Related Citations

Real-time polymerase chain reaction for the rapid detection of group B streptococcal colonization in neonates.
Authors: Natarajan G. , Johnson Y.R. , Zhang F. , Chen K.M. , Worsham M.J. .
Source: Pediatrics, 2006 Jul; 118(1), p. 14-22.
PMID: 16818544
Related Citations

High-resolution mapping of molecular events associated with immortalization, transformation, and progression to breast cancer in the MCF10 model.
Authors: Worsham M.J. , Pals G. , Schouten J.P. , Miller F. , Tiwari N. , van Spaendonk R. , Wolman S.R. .
Source: Breast Cancer Research And Treatment, 2006 Mar; 96(2), p. 177-86.
PMID: 16319984
Related Citations

Molecular classification of breast carcinoma in situ.
Authors: Raju U. , Mei L. , Seema S. , Hina Q. , Wolman S.R. , Worsham M.J. .
Source: Current Genomics, 2006; 7(8), p. 523-32.
PMID: 17375183
Related Citations

Delineating genetic pathways of disease progression in head and neck squamous cell carcinoma.
Authors: Worsham M.J. , Pals G. , Schouten J.P. , Van Spaendonk R.M. , Concus A. , Carey T.E. , Benninger M.S. .
Source: Archives Of Otolaryngology--head & Neck Surgery, 2003 Jul; 129(7), p. 702-8.
PMID: 12874067
Related Citations

Modifying a breast cancer risk factor survey for African American women.
Authors: Ford M.E. , Hill D.D. , Blount A. , Morrison J. , Worsham M. , Havstad S.L. , Johnson C.C. .
Source: Oncology Nursing Forum, 2002 Jun; 29(5), p. 827-34.
PMID: 12058157
Related Citations

Mutations in the von Hippel-Lindau (VHL) gene refine differential diagnostic criteria in renal cell carcinoma.
Authors: Barnabas N. , Amin M.B. , Pindolia K. , Nanavati R. , Amin M.B. , Worsham M.J. .
Source: Journal Of Surgical Oncology, 2002 May; 80(1), p. 52-60.
PMID: 11967908
Related Citations

Establishing a molecular continuum in breast cancer DNA microarrays and benign breast disease.
Authors: Worsham M.J. , Pals G. , Raju U. , Wolman S.R. .
Source: Cytometry, 2002-01-01 00:00:00.0; 47(1), p. 56-9.
PMID: 11774352
Related Citations

Loss of nm23 expression predicts distal metastases and poorer survival for breast cancer.
Authors: Mao H. , Liu H. , Fu X. , Fang Z. , Abrams J. , Worsham M.J. .
Source: International Journal Of Oncology, 2001 Mar; 18(3), p. 587-91.
PMID: 11179491
Related Citations

Molecular approaches to identification of tissue contamination in surgical pathology sections.
Authors: Worsham M.J. , Wolman S.R. , Zarbo R.J. .
Source: The Journal Of Molecular Diagnostics : Jmd, 2001 Feb; 3(1), p. 11-5.
PMID: 11227066
Related Citations

Detection of a single base substitution in a single cell using the LightCycler.
Authors: Pals G. , Young C. , Mao H.S. , Worsham M.J. .
Source: Journal Of Biochemical And Biophysical Methods, 2001-01-30 00:00:00.0; 47(1-2), p. 121-9.
PMID: 11179768
Related Citations

Significance of p53 mutations in patients with chronic lymphocytic leukemia: a sequential study of 30 patients.
Authors: Barnabas N. , Shurafa M. , Van Dyke D.L. , Wolman S.R. , Clark D. , Worsham M.J. .
Source: Cancer, 2001-01-15 00:00:00.0; 91(2), p. 285-93.
PMID: 11180073
Related Citations

Patterns of allelic loss at the BRCA1 locus in Arabic women with breast cancer.
Authors: Rouba A. , Kaisi N. , Al-Chaty E. , Badin R. , Pals G. , Young C. , Worsham M.J. .
Source: International Journal Of Molecular Medicine, 2000 Nov; 6(5), p. 565-9.
PMID: 11029525
Related Citations

Enhanced assessment of allogeneic bone marrow transplant engraftment using automated fluorescent-based typing.
Authors: Pindolia K. , Janakiraman N. , Kasten-Sportes C. , Demanet C. , Van Waeyenberge C. , Pals G. , Worsham M.J. .
Source: Bone Marrow Transplantation, 1999 Dec; 24(11), p. 1235-41.
PMID: 10642814
Related Citations

A rapid and sensitive approach to mutation detection using real-time polymerase chain reaction and melting curve analyses, using BRCA1 as an example.
Authors: Pals G. , Pindolia K. , Worsham M.J. .
Source: Molecular Diagnosis : A Journal Devoted To The Understanding Of Human Disease Through The Clinical Application Of Molecular Biology, 1999 Sep; 4(3), p. 241-6.
PMID: 10553024
Related Citations

Chromosomal aberrations identified in culture of squamous carcinomas are confirmed by fluorescence in situ hybridisation.
Authors: Worsham M.J. , Wolman S.R. , Carey T.E. , Zarbo R.J. , Benninger M.S. , Van Dyke D.L. .
Source: Molecular Pathology : Mp, 1999 Feb; 52(1), p. 42-6.
PMID: 10439839
Related Citations

A new BRCA1 mutation in a Filipino woman with a family history of breast and ovarian cancer.
Authors: Worsham M.J. , Nathanson S.D. , Pals G. , Christopherson P. , Strunk M. , Wolman S.R. .
Source: Diagnostic Molecular Pathology : The American Journal Of Surgical Pathology, Part B, 1998 Jun; 7(3), p. 164-7.
PMID: 9836072
Related Citations

Applications of fluorescence in situ hybridization techniques in cytopathology.
Authors: Wolman S.R. .
Source: Cancer, 1997-08-25 00:00:00.0; 81(4), p. 193-7.
PMID: 9292734
Related Citations

New directions in breast cancer research.
Authors: Wolman S.R. , Heppner G.H. , Wolman E. .
Source: Faseb Journal : Official Publication Of The Federation Of American Societies For Experimental Biology, 1997 Jun; 11(7), p. 535-43.
PMID: 9212077
Related Citations