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Multifactorial analysis of differences between sporadic breast cancers and cancers involving BRCA1 and BRCA2 mutations

Item Type:Article
Title:Multifactorial analysis of differences between sporadic breast cancers and cancers involving BRCA1 and BRCA2 mutations
Creators Name:Lakhani, S.R. and Jacquemier, J. and Sloane, J.P. and Gusterson, B.A. and Anderson, T.J. and Vandevijver, M.J. and Farid, L.M. and Venter, D. and Antoniou, A. and Storferisser, A. and Smyth, E. and Steel, C.M. and Haites, N. and Scott, R.J. and Goldgar, D. and Neuhausen, S. and Daly, P.A. and Ormiston, W. and Mcmanus, R. and Scherneck, S. and Ponder, B.A.J. and Ford, D. and Peto, J. and Stoppa-Lyonnet, D. and Bignon, Y.J. and Struewing, J.P. and Spurr, N.K. and Bishop, D.T. and Klijn, J.G.M. and Devilee, P. and Cornelisse, C.J. and Lasset, C. and Lenoir, G. and Barkardottir, R.B. and Egilsson, V. and Hamann, U. and Changclaude, J. and Sobol, H. and Weber, B. and Stratton, M.R. and Easton, D.F.
Abstract:BACKGROUND: We have previously demonstrated that breast cancers associated with inherited BRCA1 and BRCA2 gene mutations differ from each other in their histopathologic appearances and that each of these types differs from breast cancers in patients unselected for family history (i.e., sporadic cancers). We have now conducted a more detailed examination of cytologic and architectural features of these tumors. METHODS: Specimens of tumor tissue (5-microm-thick sections) were examined independently by two pathologists, who were unaware of the case or control subject status, for the presence of cell mitosis, lymphocytic infiltration, continuous pushing margins, and solid sheets of cancer cells; cell nuclei, cell nucleoli, cell necrosis, and cell borders were also evaluated. The resulting data were combined with previously available information on tumor type and tumor grade and further evaluated by multifactorial analysis. All statistical tests are two-sided. RESULTS: Cancers associated with BRCA1 mutations exhibited higher mitotic counts (P = .001), a greater proportion of the tumor with a continuous pushing margin (P<.0001), and more lymphocytic infiltration (P = .002) than sporadic (i.e., control) cancers. Cancers associated with BRCA2 mutations exhibited a higher score for tubule formation (fewer tubules) (P = .0002), a higher proportion of the tumor perimeter with a continuous pushing margin (P<.0001), and a lower mitotic count (P = .003) than control cancers. CONCLUSIONS: Our study has identified key features of the histologic phenotypes of breast cancers in carriers of mutant BRCA1 and BRCA2 genes. This information may improve the classification of breast cancers in individuals with a family history of the disease and may ultimately aid in the clinical management of patients.
Keywords:BRCA1 Genes, BRCA2 Protein, Breast Neoplasms, Multivariate Analysis, Mutation, Neoplasm Proteins, Transcription Factors
Source:Journal of the National Cancer Institute
Publisher:Oxford University Press
Page Range:1138-1145
Date:5 August 1998
Official Publication:https://doi.org/10.1093/jnci/90.15.1138
PubMed:View item in PubMed

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