Efficacy of adjuvant chemotherapy according to Prion protein expression in patients with estrogen receptor-negative breast cancer.
BACKGROUND
Prion protein (PrPc) has been previously reported to be associated with resistance to proapoptotic stimuli. We evaluated whether the expression of PrPc was associated with the resistance to adjuvant chemotherapy in patients with estrogen receptor (ER) -negative breast cancer.


METHODS
The expression of PrPc by primary tumors was assessed by immunohistochemistry in a series of 756 patients included in two randomized trials that compared anthracycline-based chemotherapy to no chemotherapy. The PrPc expression was correlated with ER expression and the benefit of adjuvant chemotherapy was assessed according to PrPc expression in patients with ER-negative tumors.


RESULTS
Immunostaining analysis showed that PrPc was mainly expressed by myoepithelial cells in normal breast tissue. Tissue microarray analysis from 756 breast tumors showed that PrPc was associated with ER-negative breast cancer subsets (P < 0.001). Adjuvant chemotherapy was not associated with a significant risk reduction for death in patients with ER-negative/PrPc-positive disease [adjusted hazard ratio (HR) for death = 0.98, 95% confidence interval (CI) 0.45-2.1, P = 0.95], while it decreased the risk for death (HR = 0.39, 95% CI 0.2-0.74, P = 0.004) in patients with ER-negative/PrPc-negative tumors.


CONCLUSIONS
These data indicate that ER-negative/PrPc-negative phenotype is associated with a high sensitivity to adjuvant chemotherapy.
Meslin
F
F
Institut National de la Santé et de la Recherche Médicale, Laboratoire d'Immunologie des Tumeurs Humaines: Interaction effecteurs cytotoxiques-système tumoral, Institut Gustave Roussy PR1 and IFR 54, 94805 Villejuif Cedex. France.
Conforti
R
R
Mazouni
C
C
Morel
N
N
Tomasic
G
G
Drusch
F
F
Yacoub
M
M
Sabourin
J C
JC
Grassi
J
J
Delaloge
S
S
Mathieu
M C
MC
Chouaib
S
S
Andre
F
F
Mehrpour
M
M
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000401:mortality* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008408:Mastectomy / Q000379:methods; D008875:Middle Aged; D018621:PrPC Proteins / Q000235:genetics / Q000378:metabolism*; D011336:Probability; D011379:Prognosis; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D011960:Receptors, Estrogen / Q000032:analysis*; D018570:Risk Assessment; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D018621:PrPC Proteins; D011960:Receptors, Estrogen