Prediction of BRCA1 status in patients with breast cancer using estrogen receptor and basal phenotype.
OBJECTIVE
To investigate the proportion of breast cancers arising in patients with germ line BRCA1 and BRCA2 mutations expressing basal markers and developing predictive tests for identification of high-risk patients.


METHODS
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.


CONCLUSIONS
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.
Lakhani
Sunil R
SR
The Breakthrough Toby Robins Breast Cancer Research Centre, Institute of Cancer Research, London, United Kingdom. s.lakhani@uq.edu.au
Reis-Filho
Jorge S
JS
Fulford
Laura
L
Penault-Llorca
Frederique
F
van der Vijver
Marc
M
Parry
Suzanne
S
Bishop
Timothy
T
Benitez
Javier
J
Rivas
Carmen
C
Bignon
Yves-Jean
YJ
Chang-Claude
Jenny
J
Hamann
Ute
U
Cornelisse
Cees J
CJ
Devilee
Peter
P
Beckmann
Matthias W
MW
Nestle-Krämling
Carolin
C
Daly
Peter A
PA
Haites
Neva
N
Varley
Jenny
J
Lalloo
Fiona
F
Evans
Gareth
G
Maugard
Christine
C
Meijers-Heijboer
Hanne
H
Klijn
Jan G M
JG
Olah
Edith
E
Gusterson
Barry A
BA
Pilotti
Silvana
S
Radice
Paolo
P
Scherneck
Siegfried
S
Sobol
Hagay
H
Jacquemier
Jocelyne
J
Wagner
Teresa
T
Peto
Julian
J
Stratton
Michael R
MR
McGuffog
Lesley
L
Easton
Douglas F
DF
D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D018095:Germ-Line Mutation; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins; D008875:Middle Aged; D015999:Multivariate Analysis; D010641:Phenotype; D011379:Prognosis; D011960:Receptors, Estrogen / Q000032:analysis*; D018570:Risk Assessment; D012680:Sensitivity and Specificity
D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; D007633:Keratins