TY - JOUR
T1 - The clinical value of somatic TP53 gene mutations in 1,794 patients with breast cancer
AU - Olivier, Magali
AU - Langerød, Anita
AU - Carrieri, Patrizia
AU - Bergh, Jonas
AU - Klaar, Sigrid
AU - Eyfjord, Jorunn
AU - Theillet, Charles
AU - Rodriguez, Carmen
AU - Lidereau, Rosette
AU - Bièche, Ivan
AU - Varley, Jennifer
AU - Bignon, Yves
AU - Uhrhammer, Nancy
AU - Winqvist, Robert
AU - Jukkola-Vuorinen, Arja
AU - Niederacher, Dieter
AU - Kato, Shunsuke
AU - Ishioka, Chikashi
AU - Hainaut, Pierre
AU - Børresen-Dale, Anne Lise
PY - 2006
Y1 - 2006
N2 - To investigate the clinical value of somatic TP53 mutations in breast cancer, we assembled clinical and molecular data on 1,794 women with primary breast cancer with long-term follow-up and whose tumor has been screened for mutation in exons 5 to 8 of TP53 by gene sequencing. TP53 mutations were more frequent in tumors of ductal and medullar types, aggressive phenotype (high grade, large size, node positive cases, and low hormone receptor content) and in women 10 years; P < 0.0001) compared with patients with no such mutation. The prognostic value of TP53 mutation was independent of tumor size, node status, and hormone receptor content, confirming and reconciling previous findings in smaller series. Moreover, an interaction between TP53 mutation and progesterone receptor (PR) status was revealed, TP53 mutation combined with the absence of progesterone receptor being associated with the worst prognosis. Whereas previous studies have emphasized the fact that missense mutations in the DNA-binding motifs have a worse prognosis than missense mutations outside these motifs, we show that non - missense mutations have prognostic value similar to missense mutations in DNA-binding motifs. Nonetheless, specific missense mutants (codon 179 and R248W) seem to be associated with an even worse prognosis. These results, obtained on the largest series analyzed thus far, show that TP53 mutations identified by gene sequencing have an independent prognostic value in breast cancer and could have potential uses in clinical practice. © 2006 American Association for Cancer Research.
AB - To investigate the clinical value of somatic TP53 mutations in breast cancer, we assembled clinical and molecular data on 1,794 women with primary breast cancer with long-term follow-up and whose tumor has been screened for mutation in exons 5 to 8 of TP53 by gene sequencing. TP53 mutations were more frequent in tumors of ductal and medullar types, aggressive phenotype (high grade, large size, node positive cases, and low hormone receptor content) and in women 10 years; P < 0.0001) compared with patients with no such mutation. The prognostic value of TP53 mutation was independent of tumor size, node status, and hormone receptor content, confirming and reconciling previous findings in smaller series. Moreover, an interaction between TP53 mutation and progesterone receptor (PR) status was revealed, TP53 mutation combined with the absence of progesterone receptor being associated with the worst prognosis. Whereas previous studies have emphasized the fact that missense mutations in the DNA-binding motifs have a worse prognosis than missense mutations outside these motifs, we show that non - missense mutations have prognostic value similar to missense mutations in DNA-binding motifs. Nonetheless, specific missense mutants (codon 179 and R248W) seem to be associated with an even worse prognosis. These results, obtained on the largest series analyzed thus far, show that TP53 mutations identified by gene sequencing have an independent prognostic value in breast cancer and could have potential uses in clinical practice. © 2006 American Association for Cancer Research.
U2 - 10.1158/1078-0432.CCR-05-1029
DO - 10.1158/1078-0432.CCR-05-1029
M3 - Article
C2 - 16489069
SN - 1078-0432
VL - 12
SP - 1157
EP - 1167
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 4
ER -