ERβ1 inversely correlates with PTEN/PI3K/AKT pathway and predicts a favorable prognosis in triple-negative breast cancer

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• 作者：Jin Wang ; Chao Zhang ; Keming Chen ; Hailin Tang…
• 关键词：ERβ1 ; Triple ; negative breast cancer ; pAKT ; PTEN ; Prognosis
• 刊名：Breast Cancer Research and Treatment
• 出版年：2015
• 出版时间：July 2015
• 年：2015
• 卷：152
• 期：2
• 页码：255-269
• 全文大小：1,510 KB
• 参考文献：1.Foulkes WD, Smith IE, Reis-Filho JS (2010) Triple-negative breast cancer. N Engl J Med 363(20):1938-948PubMed View Article
  2.Shah SP, Roth A, Goya R, Oloumi A, Ha G, Zhao Y, Turashvili G, Ding J, Tse K, Haffari G, Bashashati A, Prentice LM, Khattra J, Burleigh A, Yap D, Bernard V, McPherson A, Shumansky K, Crisan A, Giuliany R, Heravi-Moussavi A, Rosner J, Lai D, Birol I, Varhol R, Tam A, Dhalla N, Zeng T, Ma K, Chan SK, Griffith M, Moradian A, Cheng SW, Morin GB, Watson P, Gelmon K, Chia S, Chin SF, Curtis C, Rueda OM, Pharoah PD, Damaraju S, Mackey J, Hoon K, Harkins T, Tadigotla V, Sigaroudinia M, Gascard P, Tlsty T, Costello JF, Meyer IM, Eaves CJ, Wasserman WW, Jones S, Huntsman D, Hirst M, Caldas C, Marra MA, Aparicio S (2012) The clonal and mutational evolution spectrum of primary triple-negative breast cancers. Nature 486(7403):395-99PubMed
  3.Sotiriou C, Pusztai L (2009) Gene-expression signatures in breast cancer. N Engl J Med 360(8):790-00PubMed View Article
  4.O’Shaughnessy J, Schwartzberg L, Danso MA, Miller KD, Rugo HS, Neubauer M, Robert N, Hellerstedt B, Saleh M, Richards P, Specht JM, Yardley DA, Carlson RW, Finn RS, Charpentier E, Garcia-Ribas I, Winer EP (2014) Phase III study of iniparib plus gemcitabine and carboplatin versus gemcitabine and carboplatin in patients with metastatic triple-negative breast cancer. J Clin Oncol 32(34):3840-847PubMed View Article
  5.Gonzalez-Angulo AM, Akcakanat A, Liu S, Green MC, Murray JL, Chen H, Palla SL, Koenig KB, Brewster AM, Valero V, Ibrahim NK, Moulder-Thompson S, Litton JK, Tarco E, Moore J, Flores P, Crawford D, Dryden MJ, Symmans WF, Sahin A, Giordano SH, Pusztai L, Do KA, Mills GB, Hortobagyi GN, Meric-Bernstam F (2014) Open-label randomized clinical trial of standard neoadjuvant chemotherapy with paclitaxel followed by FEC versus the combination of paclitaxel and everolimus followed by FEC in women with triple receptor-negative breast cancer. Ann Oncol 25(6):1122-127PubMed Central PubMed View Article
  6.Fong PC, Boss DS, Yap TA, Tutt A, Wu P, Mergui-Roelvink M, Mortimer P, Swaisland H, Lau A, O’Connor MJ, Ashworth A, Carmichael J, Kaye SB, Schellens JH, de Bono JS (2009) Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med 361:123-34PubMed View Article
  7.Carey LA, Rugo HS, Marcom PK, Mayer EL, Esteva FJ, Ma CX, Liu MC, Storniolo AM, Rimawi MF, Forero-Torres A, Wolff AC, Hobday TJ, Ivanova A, Chiu WK, Ferraro M, Burrows E, Bernard PS, Hoadley KA, Perou CM, Winer EP (2012) TBCRC 001: randomized phase II study of cetuximab in combination with carboplatin in stage IV triple-negative breast cancer. J Clin Oncol 30(21):2615-623PubMed Central PubMed View Article
  8.Bendell JC, Rodon J, Burris HA, de Jonge M, Verweij J, Birle D, Demanse D, De Buck SS, Ru QC, Peters M, Goldbrunner M, Baselga J (2012) Phase I, dose-escalation study of BKM120, an oral pan-Class I PI3K inhibitor, in patients with advanced solid tumors. J Clin Oncol 30(3):282-90PubMed View Article
  9.Imamov O, Lopatkin NA, Gustafsson JA (2004) Estrogen receptor beta in prostate cancer. N Engl J Med 351(26):2773-774PubMed View Article
  10.Kuiper GG, Enmark E, Pelto-Huikko M, Nilsson S, Gustafsson JA (1996) Cloning of a novel receptor expressed in rat prostate and ovary. Proc Natl Acad Sci USA 93(12):5925-930PubMed Central PubMed View Article
  11.Jensen EV, Cheng G, Palmieri C, Saji S, M?kel? S, Van Noorden S, Wahlstr?m T, Warner M, Coombes RC, Gustafsson JA (2001) Estrogen receptors and proliferation markers in primary and recurrent breast cancer. Proc Natl Acad Sci USA 98(26):15197-5202PubMed Central PubMed View Article
  12.Chang EC, Frasor J, Komm B, Katzenellenbogen BS (2006) Impact of estrogen receptor beta on gene networks regulated by estrogen receptor alpha in breast cancer cells. Endocrinology 147(10):4831-842PubMed View Article
  13.Honma N, Horii R, Iwase T, Saji S, Younes M, Takubo K, Matsuura M, Ito Y, Akiyama F, Sakamoto G (2008) Clinical importance of estrogen receptor-beta evaluation in breast cancer patients treated with adjuvant tamoxifen therapy. J Clin Oncol 26(22):3727-734PubMed View Article
  14.Zhao C, Dahlman-Wright K, Gustafsson JA (2008) Estrogen receptor beta: an overview and update. Nucl Recept Signal 6:e003PubMed Central PubMed
  15.Shaaban AM, Green AR, Karthik S, Alizadeh Y, Hughes TA, Harkins L, Ellis IO, Robertson JF, Paish EC, Saunders PT, Groome NP, Speirs V (2008) Nuclear and cytoplasmic expression of ERbeta1, ERbeta2, and ERbeta5 identifies distinct prognostic outcome for breast cancer patients. Clin Cancer Res 14(16):5228-235PubMed View Article
  16.Skliris GP, Parkes AT, Limer JL, Burdall SE, Carder PJ, Speirs V (2002) Evaluation of seven oestrogen receptor beta antibodies for immunohistochemistry, western blotting, and flow cytometry in human breast tissue. J Pathol 197(2):155-62PubMed View Article
  17.Marotti JD, Collins LC, Hu R, Tamimi RM (2010)
• 作者单位：Jin Wang (1)
  Chao Zhang (2)
  Keming Chen (2)
  Hailin Tang (1)
  Jun Tang (1)
  Cailu Song (1)
  Xiaoming Xie (1)
  
  1. Department of Breast Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, No. 651 Dongfeng East Road, Yuexiu District, Guangzhou, 510060, China
  2. Department of Pathology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Yuexiu District, Guangzhou, 510060, China
  
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Oncology
  
• 出版者：Springer Netherlands
• ISSN：1573-7217

文摘

In contrast to the well-established role of estrogen receptor alpha (ERα) in breast cancer, the significance of estrogen receptor beta (ERβ) remains controversial, especially in triple-negative breast cancer (TNBC). We sought to investigate the clinical importance of wild-type ERβ (ERβ1) in TNBC based on a large population, and to explore the potential molecular pathways involved in. A total of 571 patients with invasive TNBC undergoing curative surgery were included in this study. Immunohistochemical staining for ERβ1, pAKT, PTEN, pERK, β-catenin, EGFR, p53, and E-cadherin was performed on tissue microarrays. Prognostic determinants for overall survival (OS) and disease-free survival (DFS), as well as the risk factors for distant metastasis-free survival (DMFS) and locoregional recurrence-free survival, were evaluated in univariate and multivariate analyses. Overexpression of ERβ1 was detected in 30.4?% of tumor samples. Patients with ERβ1 tended to be postmenopausal, and less likely to develop lymphatic metastasis. Multivariate analysis demonstrated that ERβ1 predicted a better OS, DFS, and DMFS independently. Regarding other biomarkers, only pAKT was identified as an independent negative predictor for survival. Additionally, ERβ1 expression was inversely associated with pAKT and the loss of PTEN. Notably, further survival analysis according to status of ERβ1/pAKT indicated that ERβ1(+)/pAKT(? predicted the most favorable prognosis for TNBC. On the contrary, ERβ1(?/pAKT(+) was associated with the worst outcomes. In summary, our findings indicate that ERβ1 independently predicts a better prognosis for TNBC and potentially interacts with the PTEN/PI3K/pAKT pathway. The role of ERβ1-specific agonists combined with the inhibitors of pAKT merits further investigation.