TY - JOUR
T1 - Prediction of BRCA1 status in patients with breast cancer using estrogen receptor and basal phenotype
AU - Lakhani, Sunil R
AU - Reis-Filho, Jorge S
AU - Fulford, Laura
AU - Penault-Llorca, Frederique
AU - van der Vijver, Marc
AU - Parry, Suzanne
AU - Bishop, Timothy
AU - Benitez, Javier
AU - Rivas, Carmen
AU - Bignon, Yves-Jean
AU - Chang-Claude, Jenny
AU - Hamann, Ute
AU - Cornelisse, Cees J
AU - Devilee, Peter
AU - Beckmann, Matthias W
AU - Nestle-Krämling, Carolin
AU - Daly, Peter A
AU - Haites, Neva
AU - Varley, Jenny
AU - Lalloo, Fiona
AU - Evans, Gareth
AU - Maugard, Christine
AU - Meijers-Heijboer, Hanne
AU - Klijn, Jan G M
AU - Olah, Edith
AU - Gusterson, Barry A
AU - Pilotti, Silvana
AU - Radice, Paolo
AU - Scherneck, Siegfried
AU - Sobol, Hagay
AU - Jacquemier, Jocelyne
AU - Wagner, Teresa
AU - Peto, Julian
AU - Stratton, Michael R
AU - McGuffog, Lesley
AU - Easton, Douglas F
AU - Breast Cancer Linkage Consortium
PY - 2005/7
Y1 - 2005/7
N2 - Purpose: To investigate the proportion of breast cancers arising inpatients with germ line BRCA1 and BRCA2 mutations expressing basal markers and developing predictive tests for identification of high-risk patients.Experimental Design: Histopathologic material from 182 tumors in BRCA1 mutation carriers, 63 BRCA2 carriers, and 109 controls, collected as part of the international Breast Cancer Linkage Consortium were immunohistochemically stained for CK14, CK5/6, CK17, epidermal growth factor receptor (EGFR), and osteonectin.Results: All five basal markers were commoner in BRCA1 tumors than in control tumors (CK14: 61% versus 12%; CK5/6: 58% versus 7%; CK17: 53% versus 10%; osteonectin: 43% versus 19%; EGFR: 67% versus 21%; P < 0.0001 in each case). In a multivariate analysis, CK14, CK5/6, and estrogen receptor (ER) remained significant predictors of BRCA1 carrier status. In contrast, the frequency of basal markers in BRCA2 tumors did not differ significant from controls.Conclusion: The use of cytokeratin staining in combination with ER and morphology provides a more accurate predictor of BRCA1 mutation status than previously available, that may be useful in selecting patients for BRCA1 mutation testing. The high percentage of BRCA1 cases positive for EGFR suggests that specific anti-tyrosine kinase therapy may be of potential benefit in these patients.
AB - Purpose: To investigate the proportion of breast cancers arising inpatients with germ line BRCA1 and BRCA2 mutations expressing basal markers and developing predictive tests for identification of high-risk patients.Experimental Design: Histopathologic material from 182 tumors in BRCA1 mutation carriers, 63 BRCA2 carriers, and 109 controls, collected as part of the international Breast Cancer Linkage Consortium were immunohistochemically stained for CK14, CK5/6, CK17, epidermal growth factor receptor (EGFR), and osteonectin.Results: All five basal markers were commoner in BRCA1 tumors than in control tumors (CK14: 61% versus 12%; CK5/6: 58% versus 7%; CK17: 53% versus 10%; osteonectin: 43% versus 19%; EGFR: 67% versus 21%; P < 0.0001 in each case). In a multivariate analysis, CK14, CK5/6, and estrogen receptor (ER) remained significant predictors of BRCA1 carrier status. In contrast, the frequency of basal markers in BRCA2 tumors did not differ significant from controls.Conclusion: The use of cytokeratin staining in combination with ER and morphology provides a more accurate predictor of BRCA1 mutation status than previously available, that may be useful in selecting patients for BRCA1 mutation testing. The high percentage of BRCA1 cases positive for EGFR suggests that specific anti-tyrosine kinase therapy may be of potential benefit in these patients.
KW - invasive ductal carcinomas
KW - gene-expression profiles
KW - central acellular zones
KW - myoepithelial cells
KW - prognostic markers
KW - mutations
KW - differentiation
KW - pathology
KW - disease
KW - benign
U2 - 10.1158/1078-0432.CCR-04-2424
DO - 10.1158/1078-0432.CCR-04-2424
M3 - Article
C2 - 16033833
SN - 1078-0432
VL - 11
SP - 5175
EP - 5180
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 14
ER -
