p53 accumulation is a strong predictor of recurrence in estrogen receptor-positive breast cancer patients treated with aromatase inhibitors.
p53 accumulation is a strong predictor of recurrence in estrogen receptor-positive breast cancer patients treated with aromatase inhibitors.
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DOI：
10.1111/cas.12302
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发表时间：
2014-01
期刊：
影响因子：
5.7
通讯作者：
Yamashita H
中科院分区：
文献类型：
--
作者：
Yamamoto M;Hosoda M;Nakano K;Jia S;Hatanaka KC;Takakuwa E;Hatanaka Y;Matsuno Y;Yamashita H
芳香酶抑制剂在绝经后女性雌激素受体（ER）阳性乳腺癌的内分泌治疗中发挥着核心作用。然而，尚未确定芳香酶抑制剂疗效的预测因素以及接受辅助芳香酶抑制剂治疗的女性早期和晚期复发的预后因素。全基因组分析发现，ER 阳性乳腺癌中存在 TP53 基因突变，尽管管腔肿瘤中 TP53 基因突变的频率低于基底细胞样或人表皮生长因子受体 2 型 (HER2) 阳性乳腺癌。我们使用免疫组织化学方法检测了接受芳香酶抑制剂作为辅助内分泌治疗的绝经后 ER 阳性乳腺癌患者中 p53 以及 ER、孕激素受体、HER2 和 Ki-67 的表达。有 53 个 (21%) 肿瘤含有 10% 或更多的 p53 阳性细胞。 p53高表达与肿瘤分级、HER2评分和Ki-67表达呈正相关。多变量分析中观察到无病生存率与高 p53 表达之间存在显着相关性 (P < 0.0001)。与未复发的女性相比，早期复发的女性的 p53 表达显着较高（P < 0.0001），晚期复发的女性也是如此（P = 0.037）。本研究表明，p53 积累是接受芳香酶抑制剂辅助内分泌治疗的 ER 阳性乳腺癌患者早期和晚期复发的有力预测因子。 TP53基因改变可能是ER阳性乳腺癌的一个关键生物学特征。
Aromatase inhibitors have played a central role in endocrine therapy for estrogen receptor (ER)-positive breast cancer in postmenopausal women. However, factors predictive of the efficacy of aromatase inhibitors, and prognostic factors, both for early and late recurrence in women treated with adjuvant aromatase inhibitors have not been identified. Whole genome analysis identified that a TP53 gene mutation exists in ER-positive breast cancers, although the frequency of TP53 gene mutation in luminal tumors is lower compared with basal-like or human epidermal growth factor receptor type 2 (HER2)-positive breast cancers. We examined expression of p53, as well as ER, progesterone receptor, HER2 and Ki-67 using immunohistochemistry in postmenopausal ER-positive breast cancer patients who were treated with aromatase inhibitors as adjuvant endocrine therapy. There were 53 (21%) tumors that contained 10% or more p53-positive cells. High p53 expression was positively correlated with tumor grade, HER2 score and Ki-67 expression. Significant association was observed between disease-free survival and high p53 expression in multivariate analysis (P < 0.0001). Compared with women without recurrence, women with early recurrence had significantly higher p53 expression (P < 0.0001), as did women with late recurrence (P = 0.037). The present study demonstrates that p53 accumulation is a strong predictor of both early and late recurrence in ER-positive breast cancer patients treated with aromatase inhibitors as adjuvant endocrine therapy. TP53 gene alteration might be a key biological characteristic of ER-positive breast cancer.
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影响因子：
64.8
作者：
Ellis, Matthew J.;Ding, Li;Shen, Dong;Luo, Jingqin;Suman, Vera J.;Wallis, John W.;Van Tine, Brian A.;Hoog, Jeremy;Goiffon, Reece J.;Goldstein, Theodore C.;Ng, Sam;Lin, Li;Crowder, Robert;Snider, Jacqueline;Ballman, Karla;Weber, Jason;Chen, Ken;Koboldt, Daniel C.;Kandoth, Cyriac;Schierding, William S.;McMichael, Joshua F.;Miller, Christopher A.;Lu, Charles;Harris, Christopher C.;McLellan, Michael D.;Wendl, Michael C.;DeSchryver, Katherine;Allred, D. Craig;Esserman, Laura;Unzeitig, Gary;Margenthaler, Julie;Babiera, G. V.;Marcom, P. Kelly;Guenther, J. M.;Leitch, Marilyn;Hunt, Kelly;Olson, John;Tao, Yu;Maher, Christopher A.;Fulton, Lucinda L.;Fulton, Robert S.;Harrison, Michelle;Oberkfell, Ben;Du, Feiyu;Demeter, Ryan;Vickery, Tammi L.;Elhammali, Adnan;Piwnica-Worms, Helen;McDonald, Sandra;Watson, Mark;Dooling, David J.;Ota, David;Chang, Li-Wei;Bose, Ron;Ley, Timothy J.;Piwnica-Worms, David;Stuart, Joshua M.;Wilson, Richard K.;Mardis, Elaine R.
通讯作者：
Mardis, Elaine R.
影响因子：
45.3
作者：
Bartlett, John M. S.;Bloom, Kenneth J.;Rea, Daniel
通讯作者：
Rea, Daniel
影响因子：
--
作者：
Kobayashi T;Iwaya K;Moriya T;Yamasaki T;Tsuda H;Yamamoto J;Matsubara O
通讯作者：
Matsubara O
影响因子：
45.3
作者：
Hugh, Judith;Hanson, John;Vogel, Charles
通讯作者：
Vogel, Charles
影响因子：
45.3
作者：
Penault-Llorca, Frederique;Andre, Fabrice;Roche, Henri
通讯作者：
Roche, Henri