イワモト　タカユキ   Takayuki Iwamoto   岩本　高行    所属   川崎医科大学  医学部 臨床医学　乳腺甲状腺外科学    職種   講師
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Distinct p53 gene signatures are needed to predict prognosis and response to chemotherapy in ER-positive and ER-negative breast cancers.
掲載誌名	正式名：Clinical cancer research : an official journal of the American Association for Cancer Research 略　 称：Clin Cancer Res ISSNコード：15573265/10780432
掲載区分	国外
巻・号・頁	17(8),pp.2591-601
著者・共著者	Charles Coutant, Roman Rouzier, Yuan Qi, Jacqueline Lehmann-Che, Giampaolo Bianchini, Takayuki Iwamoto, Gabriel N Hortobagyi, W Fraser Symmans, Serge Uzan, Fabrice Andre, Hugues de Thé, Lajos Pusztai
発行年月	2011/04
概要	PURPOSE:Estrogen receptor-positive (ER+) and -negative (ER) breast cancers are molecularly distinct diseases. We hypothesized that p53 mutations may lead to different transcriptional changes and carry different prognostic value in these two different types of cancers.EXPERIMENTAL DESIGN:We developed a 39-gene p53 signature derived from 213 ER+ and a separate 30-gene signature from 38 ER- cancers with known mutation status and tested their prognostic and chemotherapy response predictive values in ER+ and ER- cancers, respectively.RESULTS:External validation to predict p53 status (n = 103) showed sensitivity and specificity of 89% and 54% for the 39-gene signature, and 82% and 61% for the 30-gene signature. The 39-gene signature was predictive of worse distant metastasis free survival in ER+ cancers in two separate prognostic data sets (n = 255, HR: 2.3, P = 0.005 and n = 198, HR: 2.17, P = 0.09). It also predicted for poor prognosis even with adjuvant tamoxifen therapy (n = 277, HR = 2.43, P < 0.0001) but it was not prognostic in ER- cancers. It was also associated with higher chemotherapy sensitivity in ER+ but not in ER- cancers. The prognostic and predictive values remained significant in multivariate analysis. The 30-gene, ER-, p53 signature showed no prognostic or predictive values in ER+ cancers but it was associated with better prognosis in ER- cancers. It also had no chemotherapy response predictive value in ER- or ER+ cancers.CONCLUSIONS:P53 dysfunction is prognostically most relevant in ER+ cancers and supports the hypothesis that different predictive or prognostic markers will be needed for different molecular subsets of breast cancer.
DOI	10.1158/1078-0432.CCR-10-1045
PMID	21248301