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

Lakhani, Sunil R., Jacquemier, Jocelyne, Sloane, John P, Gusterson, Barry A., Anderson, Thomas J., van de Vijver, Marc J., Farid, Linda M., Venter, Deon, Antoniou, Antonios, Storfer-Isser, Amy, Smyth, Elizabeth, Steel, C. Michael, Haites, Neva, Scott, Rodney J., Goldgar, David, Neuhausen, Susan, Daly, Peter A., Ormiston, Wilma, McManus, Ross, Scherneck, Siegfried, Ponder, Bruce A. J., Ford, Debbie, Peto, Julian, Stoppa-Lyonnet, Dominique, Bignon, Yves-Jean, Struewing, Jeffrey P., Spurr, Nigel K., Bishop, D. Timothy, Klijn, J. G. M., Devilee, Peter, Cornelisse, Cornelisse J., Lasset, Christine, Lenoir, Gilbert, Barkardottir, Rosa Bjork, Egilsson, Valgurdur, Hamann, Ute, Chang-Claude, Jenny, Sobol, Hagay, Weber, Barbara, Stratton, Michael R. and Easton, Douglas F. (1998) Multifactorial analysis of differences between sporadic breast cancers and cancers involving BRCA1 and BRCA2 mutations. Journal of the National Cancer Institute, 90 15: 1138-1145. doi:10.1093/jnci/90.15.1138

Author Lakhani, Sunil R.
Jacquemier, Jocelyne
Sloane, John P
Gusterson, Barry A.
Anderson, Thomas J.
van de Vijver, Marc J.
Farid, Linda M.
Venter, Deon
Antoniou, Antonios
Storfer-Isser, Amy
Smyth, Elizabeth
Steel, C. Michael
Haites, Neva
Scott, Rodney J.
Goldgar, David
Neuhausen, Susan
Daly, Peter A.
Ormiston, Wilma
McManus, Ross
Scherneck, Siegfried
Ponder, Bruce A. J.
Ford, Debbie
Peto, Julian
Stoppa-Lyonnet, Dominique
Bignon, Yves-Jean
Struewing, Jeffrey P.
Spurr, Nigel K.
Bishop, D. Timothy
Klijn, J. G. M.
Devilee, Peter
Cornelisse, Cornelisse J.
Lasset, Christine
Lenoir, Gilbert
Barkardottir, Rosa Bjork
Egilsson, Valgurdur
Hamann, Ute
Chang-Claude, Jenny
Sobol, Hagay
Weber, Barbara
Stratton, Michael R.
Easton, Douglas F.
Title Multifactorial analysis of differences between sporadic breast cancers and cancers involving BRCA1 and BRCA2 mutations
Journal name Journal of the National Cancer Institute   Check publisher's open access policy
ISSN 0027-8874
Publication date 1998-08
Sub-type Article (original research)
DOI 10.1093/jnci/90.15.1138
Volume 90
Issue 15
Start page 1138
End page 1145
Total pages 8
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Language eng
Formatted 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-μm-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.
Keyword Susceptibility gene
Medullary carcinoma
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Faculty of Health and Behavioural Sciences -- Publications
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