Epigenetic modulation: a novel therapeutic target for overcoming hormonal therapy resistance

• Hsu PY , HsuHK, SingerGAet al. Estrogen-mediated epigenetic repression of large chromosomal regions through DNA looping. Genome Res. 20(6) , 733–744 (2010).
   PubMed Web of Science ®Google Scholar
• Reik W . Stability and flexibility of epigenetic gene regulation in mammalian development. Nature447(7143) , 425–432 (2007).
   PubMed Web of Science ®Google Scholar
• Berdasco M , EstellerM. Aberrant epigenetic landscape in cancer: how cellular identity goes awry. Dev. Cell19(5) , 698–711 (2010).
   PubMed Web of Science ®Google Scholar
• Jemal A , SiegelR, XuJ, WardE. Cancer statistics. CA Cancer J. Clin.60(5) , 277–300 (2010).
   PubMed Web of Science ®Google Scholar
• Thomas S , MunsterPN. Histone deacetylase inhibitor induced modulation of antiestrogen therapy. Cancer Lett.280(2) , 184–191 (2009).
   PubMed Web of Science ®Google Scholar
• Woodcock CL , GhoshRP. Chromatin higher-order structure and dynamics. Cold Spring Harb. Perspect. Biol.2(5) , a000596 (2010).
   PubMedGoogle Scholar
• Pradhan S , BacollaA, WellsRD, RobertsRJ. Recombinant human DNA (cytosine-5) methyltransferase. I. Expression, purification, and comparison of de novo and maintenance methylation. J. Biol. Chem.274(46) , 33002–33010 (1999).
   PubMed Web of Science ®Google Scholar
• Okano M , BellDW, HaberDA, LiE. DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell99(3) , 247–257 (1999).
   PubMed Web of Science ®Google Scholar
• Bird AP , WolffeAP. Methylation-induced repression – belts, braces, and chromatin. Cell99(5) , 451–454 (1999).
   PubMed Web of Science ®Google Scholar
• Kouzarides T . Chromatin modifications and their function. Cell128(4) , 693–705 (2007).
   PubMed Web of Science ®Google Scholar
• Jenuwein T , AllisCD. Translating the histone code. Science293(5532) , 1074–1080 (2001).
   PubMed Web of Science ®Google Scholar
• Jones PA , BaylinSB. The epigenomics of cancer. Cell128(4) , 683–692 (2007).
   PubMed Web of Science ®Google Scholar
• Beisel C , ParoR. Silencing chromatin: comparing modes and mechanisms. Nat. Rev. Genet.12(2) , 123–135 (2011).
   PubMed Web of Science ®Google Scholar
• Lee RC , FeinbaumRL, AmbrosV. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell75(5) , 843–854 (1993).
   PubMed Web of Science ®Google Scholar
• Reinhart BJ , SlackFJ, BassonMet al. The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature 403(6772) , 901–906 (2000).
   PubMed Web of Science ®Google Scholar
• Hawkins PG , MorrisKV. RNA and transcriptional modulation of gene expression. Cell Cycle7(5) , 602–607 (2008).
   PubMed Web of Science ®Google Scholar
• Fabbri M , GarzonR, CimminoAet al. MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B. Proc. Natl Acad. Sci. USA 104(40) , 15805–15810 (2007).
   PubMed Web of Science ®Google Scholar
• Friedman JM , LiangG, LiuCCet al. The putative tumor suppressor microRNA-101 modulates the cancer epigenome by repressing the polycomb group protein EZH2. Cancer Res. 69(6) , 2623–2629 (2009).
   PubMed Web of Science ®Google Scholar
• Noonan EJ , PlaceRF, PookotDet al. miR-449a targets HDAC-1 and induces growth arrest in prostate cancer. Oncogene 28(14) , 1714–1724 (2009).
   PubMed Web of Science ®Google Scholar
• Garzon R , LiuS, FabbriMet al. MicroRNA-29b induces global DNA hypomethylation and tumor suppressor gene reexpression in acute myeloid leukemia by targeting directly DNMT3A and 3B and indirectly DNMT1. Blood 113(25) , 6411–6418 (2009).
   PubMed Web of Science ®Google Scholar
• Szulwach KE , LiX, SmrtRDet al. Cross talk between microRNA and epigenetic regulation in adult neurogenesis. J. Cell Biol. 189(1) , 127–141 (2010).
   PubMed Web of Science ®Google Scholar
• Saito Y , LiangG, EggerGet al. Specific activation of microRNA-127 with downregulation of the proto-oncogene BCL6 by chromatin-modifying drugs in human cancer cells. Cancer Cell 9(6) , 435–443 (2006).
   PubMed Web of Science ®Google Scholar
• Furuta M , KozakiKI, TanakaS, AriiS, ImotoI, InazawaJ. miR-124 and miR-203 are epigenetically silenced tumor-suppressive microRNAs in hepatocellular carcinoma. Carcinogenesis31(5) , 766–776 (2010).
   PubMed Web of Science ®Google Scholar
• Di Leva G , GaspariniP, PiovanCet al. MicroRNA cluster 221–222 and estrogen receptor α interactions in breast cancer. J. Natl Cancer Inst. 102(10) , 706–721 (2010).
   PubMed Web of Science ®Google Scholar
• Tsai KW , KaoHW, ChenHC, ChenSJ, LinWC. Epigenetic control of the expression of a primate-specific microRNA cluster in human cancer cells. Epigenetics4(8) , 587–592 (2009).
   PubMed Web of Science ®Google Scholar
• Jones PA , TaylorSM. Cellular differentiation, cytidine analogs and DNA methylation. Cell20(1) , 85–93 (1980).
   PubMed Web of Science ®Google Scholar
• Issa JP , KantarjianHM. Targeting DNA methylation. Clin. Cancer Res.15(12) , 3938–3946 (2009).
   PubMed Web of Science ®Google Scholar
• Marks PA , RichonVM, RifkindRA. Histone deacetylase inhibitors: inducers of differentiation or apoptosis of transformed cells. J. Natl Cancer Inst.92(15) , 1210–1216 (2000).
   PubMed Web of Science ®Google Scholar
• Thurn KT , ThomasS, MooreA, MunsterPN. Rational therapeutic combinations with histone deacetylase inhibitors for the treatment of cancer. Future Oncol.7(2) , 263–283 (2011).
   PubMed Web of Science ®Google Scholar
• Thomas S , MillerA, ThurnKT, MunsterPN. Clinical applications of histone deacetylase inhibitors. In: Handbook of Epigenetics: N. Mol. Med. Genet. Tollefsbol T (Eds). Academic Press, London, UK, 597–615 (2011).
   Google Scholar
• Hsu PY , DeatherageDE, RodriguezBAet al. Xenoestrogen-induced epigenetic repression of microRNA-9-3 in breast epithelial cells. Cancer Res. 69(14) , 5936–5945 (2009).
   PubMed Web of Science ®Google Scholar
• Clarke RB , HowellA, PottenCS, AndersonE. Dissociation between steroid receptor expression and cell proliferation in the human breast. Cancer Res.57(22) , 4987–4991 (1997).
   PubMed Web of Science ®Google Scholar
• Sommer S , FuquaSA. Estrogen receptor and breast cancer. Semin. Cancer Biol.11(5) , 339–352 (2001).
   PubMed Web of Science ®Google Scholar
• Zilli M , GrassadoniaA, TinariNet al. Molecular mechanisms of endocrine resistance and their implication in the therapy of breast cancer. Biochim. Biophys. Acta 1795(1) , 62–81 (2009).
   PubMed Web of Science ®Google Scholar
• Osborne CK , SchiffR, FuquaSA, ShouJ. Estrogen receptor: current understanding of its activation and modulation. Clin. Cancer Res.7(Suppl. 12) , 4338s–4342s; discussion 4411s–4412s (2001).
   PubMed Web of Science ®Google Scholar
• Merrell KW , CroftsJD, SmithRLet al. Differential recruitment of nuclear receptor coregulators in ligand-dependent transcriptional repression by estrogen receptor-α. Oncogene 30(13) , 1608–1614 (2011).
   PubMed Web of Science ®Google Scholar
• O‘Lone R , FrithMC, KarlssonEK, HansenU. Genomic targets of nuclear estrogen receptors. Mol. Endocrinol.18(8) , 1859–1875 (2004).
   PubMedGoogle Scholar
• Marino M , GalluzzoP, AscenziP. Estrogen signaling multiple pathways to impact gene transcription. Curr. Genomics7(8) , 497–508 (2006).
   PubMed Web of Science ®Google Scholar
• Wei LN , HuX, ChandraD, SetoE, FarooquiM. Receptor-interacting protein 140 directly recruits histone deacetylases for gene silencing. J. Biol. Chem.275(52) , 40782–40787 (2000).
   PubMed Web of Science ®Google Scholar
• Guenther MG , BarakO, LazarMA. The SMRT and N-CoR corepressors are activating cofactors for histone deacetylase 3. Mol. Cell. Biol.21(18) , 6091–6101 (2001).
   PubMed Web of Science ®Google Scholar
• Levin ER . Cell localization, physiology, and nongenomic actions of estrogen receptors. J. Appl. Physiol.91(4) , 1860–1867 (2001).
   PubMed Web of Science ®Google Scholar
• Castoria G , MigliaccioA, BilancioAet al. PI3-kinase in concert with Src promotes the S-phase entry of oestradiol-stimulated MCF-7 cells. EMBO J. 20(21) , 6050–6059 (2001).
   PubMed Web of Science ®Google Scholar
• Pedram A , RazandiM, SainsonRC, KimJK, HughesCC, LevinER. A conserved mechanism for steroid receptor translocation to the plasma membrane. J. Biol. Chem.282(31) , 22278–22288 (2007).
   PubMed Web of Science ®Google Scholar
• Schiff R , MassarwehSA, ShouJet al. Advanced concepts in estrogen receptor biology and breast cancer endocrine resistance: implicated role of growth factor signaling and estrogen receptor coregulators. Cancer Chemother. Pharmacol. 56(Suppl. 1) , 10–20 (2005).
   PubMed Web of Science ®Google Scholar
• Mcdonnell DP . The molecular pharmacology of estrogen receptor modulators: implications for the treatment of breast cancer. Clinical Cancer Res.11(2 Pt 2) , 871s–877s (2005).
   PubMed Web of Science ®Google Scholar
• Jordan VC . Tamoxifen: a most unlikely pioneering medicine. Nat. Rev. Drug Discov.2(3) , 205–213 (2003).
   PubMed Web of Science ®Google Scholar
• Kato S , EndohH, MasuhiroYet al. Activation of the estrogen receptor through phosphorylation by mitogen-activated protein kinase. Science 270(5241) , 1491–1494 (1995).
   PubMed Web of Science ®Google Scholar
• Kumar V , GreenS, StackG, BerryM, JinJR, ChambonP. Functional domains of the human estrogen receptor. Cell51(6) , 941–951 (1987).
   PubMed Web of Science ®Google Scholar
• Osborne CK . Tamoxifen in the treatment of breast cancer. N. Engl. J. Med.339(22) , 1609–1618 (1998).
   PubMed Web of Science ®Google Scholar
• Fawell SE , WhiteR, HoareS, SydenhamM, PageM, ParkerMG. Inhibition of estrogen receptor-DNA binding by the ‘pure‘ antiestrogen ICI 164,384 appears to be mediated by impaired receptor dimerization. Proc. Natl Acad. Sci. USA87(17) , 6883–6887 (1990).
   PubMed Web of Science ®Google Scholar
• Dauvois S , DanielianPS, WhiteR, ParkerMG. Antiestrogen ICI 164,384 reduces cellular estrogen receptor content by increasing its turnover. Proc. Natl Acad. Sci. USA89(9) , 4037–4041 (1992).
   PubMed Web of Science ®Google Scholar
• Dauvois S , WhiteR, ParkerMG. The antiestrogen ICI 182780 disrupts estrogen receptor nucleocytoplasmic shuttling. J. Cell. Sci.106(Pt 4) , 1377–1388 (1993).
   PubMed Web of Science ®Google Scholar
• Kedar RP , BourneTH, PowlesTJet al. Effects of tamoxifen on uterus and ovaries of postmenopausal women in a randomised breast cancer prevention trial. Lancet 343(8909) , 1318–1321 (1994).
   PubMed Web of Science ®Google Scholar
• Anderson WF , ChatterjeeN, ErshlerWB, BrawleyOW. Estrogen receptor breast cancer phenotypes in the Surveillance, Epidemiology, and End Results database. Breast Cancer Res. Treat.76(1) , 27–36 (2002).
   PubMed Web of Science ®Google Scholar
• Sorlie T , TibshiraniR, ParkerJet al. Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc. Natl Acad. Sci. USA 100(14) , 8418–8423 (2003).
   PubMed Web of Science ®Google Scholar
• Sorlie T , PerouCM, TibshiraniRet al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc. Natl Acad. Sci. USA 98(19) , 10869–10874 (2001).
   PubMed Web of Science ®Google Scholar
• Hammond ME , HayesDF, WolffAC, ManguPB, TeminS. American society of clinical oncology/college of american pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J. Oncol. Pract.6(4) , 195–197 (2010).
   PubMedGoogle Scholar
• Arpino G , WeissH, LeeAVet al. Estrogen receptor-positive, progesterone receptor-negative breast cancer: association with growth factor receptor expression and tamoxifen resistance. J. Natl Cancer Inst. 97(17) , 1254–1261 (2005).
   PubMedGoogle Scholar
• Wolff AC , HammondME, SchwartzJNet al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J. Clin. Oncol. 25(1) , 118–145 (2007).
   PubMed Web of Science ®Google Scholar
• Mcguire WL . Hormone receptors: their role in predicting prognosis and response to endocrine therapy. Semin. Oncol.5(4) , 428–433 (1978).
   PubMed Web of Science ®Google Scholar
• Zhang QX , BorgA, WolfDM, OesterreichS, FuquaSA. An estrogen receptor mutant with strong hormone-independent activity from a metastatic breast cancer. Cancer Res.57(7) , 1244–1249 (1997).
   PubMed Web of Science ®Google Scholar
• Tebbit CL , BentleyRC, OlsonJA Jr, Marks JR. Estrogen receptor α (ESR1) mutant A908G is not a common feature in benign and malignant proliferations of the breast. Genes Chromosomes Cancer40(1) , 51–54 (2004).
   PubMed Web of Science ®Google Scholar
• Nielsen KV , EjlertsenB, MullerSet al. Amplification of ESR1 may predict resistance to adjuvant tamoxifen in postmenopausal patients with hormone receptor positive breast cancer. Breast Cancer Res. Treat. 127(2) , 345–355 (2011).
   PubMed Web of Science ®Google Scholar
• Roodi N , BaileyLR, KaoWYet al. Estrogen receptor gene analysis in estrogen receptor-positive and receptor-negative primary breast cancer. J. Natl Cancer Inst. 87(6) , 446–451 (1995).
   PubMedGoogle Scholar
• Al-Bader M , Al-SajiS, FordCH, FrancisI, Al-AyadhyB. Real-time PCR: detection of oestrogen receptor-α and -β isoforms and variants in breast cancer. Anticancer Res.30(10) , 4147–4156 (2010).
   PubMed Web of Science ®Google Scholar
• Ando Y , IwaseH, IchiharaSet al. Loss of heterozygosity and microsatellite instability in ductal carcinoma in situ of the breast. Cancer Lett. 156(2) , 207–214 (2000).
   PubMed Web of Science ®Google Scholar
• Parl FF , CavenerDR, DupontWD. Genomic DNA analysis of the estrogen receptor gene in breast cancer. Breast Cancer Res. Treat.14(1) , 57–64 (1989).
   PubMed Web of Science ®Google Scholar
• Otis CN , KrebsPA, AlbuquerqueAet al. Loss of heterozygosity of p53, BRCA1, VHL, and estrogen receptor genes in breast carcinoma: correlation with related protein products and morphologic features. Int. J. Surg. Pathol. 10(4) , 237–245 (2002).
   PubMed Web of Science ®Google Scholar
• Ottaviano YL , IssaJP, ParlFF, SmithHS, BaylinSB, DavidsonNE. Methylation of the estrogen receptor gene CpG island marks loss of estrogen receptor expression in human breast cancer cells. Cancer Res.54(10) , 2552–2555 (1994).
   PubMed Web of Science ®Google Scholar
• Macaluso M , CintiC, RussoG, RussoA, GiordanoA. pRb2/p130-E2F4/5-HDAC1-SUV39H1-p300 and pRb2/p130-E2F4/5-HDAC1-SUV39H1-DNMT1 multimolecular complexes mediate the transcription of estrogen receptor-α in breast cancer. Oncogene22(23) , 3511–3517 (2003).
   PubMed Web of Science ®Google Scholar
• Sharma D , BlumJ, YangX, BeaulieuN, MacleodAR, DavidsonNE. Release of methyl CpG binding proteins and histone deacetylase 1 from the estrogen receptor α (ER) promoter upon reactivation in ER-negative human breast cancer cells. Mol. Endocrinol.19(7) , 1740–1751 (2005).
   PubMedGoogle Scholar
• Wei M , XuJ, DignamJet al. Estrogen receptor α, BRCA1, and FANCF promoter methylation occur in distinct subsets of sporadic breast cancers. Breast Cancer Res. Treat. 111(1) , 113–120 (2008).
   PubMed Web of Science ®Google Scholar
• Kawai H , LiH, AvrahamS, JiangS, AvrahamHK. Overexpression of histone deacetylase HDAC1 modulates breast cancer progression by negative regulation of estrogen receptor α. Int. J. Cancer107(3) , 353–358 (2003).
   PubMed Web of Science ®Google Scholar
• Lapidus RG , FergusonAT, OttavianoYLet al. Methylation of estrogen and progesterone receptor gene 5´ CpG islands correlates with lack of estrogen and progesterone receptor gene expression in breast tumors. Clin. Cancer Res. 2(5) , 805–810 (1996).
   PubMed Web of Science ®Google Scholar
• Hori M , IwasakiM, YoshimiF, AsatoY, ItabashiM. Hypermethylation of the estrogen receptor α gene is not related to lack of receptor protein in human breast cancer. Breast Cancer6(2) , 79–86 (1999).
   PubMedGoogle Scholar
• Iwase H , OmotoY, IwataHet al. DNA methylation analysis at distal and proximal promoter regions of the oestrogen receptor gene in breast cancers. Br. J. Cancer 80(12) , 1982–1986 (1999).
   PubMed Web of Science ®Google Scholar
• Zhao L , WangL, JinFet al. Silencing of estrogen receptor α (ERα) gene by promoter hypermethylation is a frequent event in Chinese women with sporadic breast cancer. Breast Cancer Res. Treat. 117(2) , 253–259 (2009).
   PubMed Web of Science ®Google Scholar
• Girault I , TozluS, LidereauR, BiecheI. Expression analysis of DNA methyltransferases 1, 3A, and 3B in sporadic breast carcinomas. Clin. Cancer Res.9(12) , 4415–4422 (2003).
   PubMed Web of Science ®Google Scholar
• Yoshida T , EguchiH, NakachiKet al. Distinct mechanisms of loss of estrogen receptor α gene expression in human breast cancer: methylation of the gene and alteration of trans-acting factors. Carcinogenesis 21(12) , 2193–2201 (2000).
   PubMed Web of Science ®Google Scholar
• Radojicic J , ZaravinosA, VrekoussisT, KafousiM, SpandidosDA, StathopoulosEN. MicroRNA expression analysis in triple-negative (ER, PR and Her2/neu) breast cancer. Cell Cycle10(3) , 507–517 (2011).
   PubMed Web of Science ®Google Scholar
• Hannafon BN , SebastianiP, De Las Morenas A, Lu J, Rosenberg CL. Expression of microRNA and their gene targets are dysregulated in preinvasive breast cancer. Breast Cancer Res.13(2) , R24 (2011).
   PubMedGoogle Scholar
• Bockmeyer CL , ChristgenM, MullerMet al. MicroRNA profiles of healthy basal and luminal mammary epithelial cells are distinct and reflected in different breast cancer subtypes. Breast Cancer Res. Treat. DOI: 10.1007/s10549-010-1303-3 (2011) (Epub ahead of print).
   PubMed Web of Science ®Google Scholar
• Adams BD , FurneauxH, WhiteBA. The micro-ribonucleic acid (miRNA) miR-206 targets the human estrogen receptor-α (ERα) and represses ERα messenger RNA and protein expression in breast cancer cell lines. Mol. Endocrinol.21(5) , 1132–1147 (2007).
   PubMed Web of Science ®Google Scholar
• Zhao JJ , LinJ, YangHet al. MicroRNA-221/222 negatively regulates estrogen receptor α and is associated with tamoxifen resistance in breast cancer. J. Biol. Chem. 283(45) , 31079–31086 (2008).
   PubMed Web of Science ®Google Scholar
• Pandey DP , PicardD. miR-22 inhibits estrogen signaling by directly targeting the estrogen receptor α mRNA. Mol. Cell. Biol.29(13) , 3783–3790 (2009).
   PubMed Web of Science ®Google Scholar
• Xiong J , YuD, WeiNet al. An estrogen receptor α suppressor, microRNA-22, is downregulated in estrogen receptor α-positive human breast cancer cell lines and clinical samples. FEBS J. 277(7) , 1684–1694 (2010).
   PubMed Web of Science ®Google Scholar
• Toi M , NakamuraT, MukaidaHet al. Relationship between epidermal growth factor receptor status and various prognostic factors in human breast cancer. Cancer 65(9) , 1980–1984 (1990).
   PubMed Web of Science ®Google Scholar
• Klijn JG , BernsPM, SchmitzPI, FoekensJA. The clinical significance of epidermal growth factor receptor (EGF-R) in human breast cancer: a review on 5232 patients. Endocr. Rev.13(1) , 3–17 (1992).
   PubMed Web of Science ®Google Scholar
• Sharma AK , HorganK, Douglas-JonesA, McclellandR, GeeJ, NicholsonR. Dual immunocytochemical analysis of oestrogen and epidermal growth factor receptors in human breast cancer. Br. J. Cancer69(6) , 1032–1037 (1994).
   PubMed Web of Science ®Google Scholar
• Van Agthoven T , TimmermansM, FoekensJA, DorssersLC, Henzen-LogmansSC. Differential expression of estrogen, progesterone, and epidermal growth factor receptors in normal, benign, and malignant human breast tissues using dual staining immunohistochemistry. Am. J. Pathol.144(6) , 1238–1246 (1994).
   PubMed Web of Science ®Google Scholar
• Pietras RJ , ArboledaJ, ReeseDMet al. HER-2 tyrosine kinase pathway targets estrogen receptor and promotes hormone-independent growth in human breast cancer cells. Oncogene 10(12) , 2435–2446 (1995).
   PubMed Web of Science ®Google Scholar
• Tang CK , PerezC, GruntT, WaibelC, ChoC, LupuR. Involvement of heregulin-β2 in the acquisition of the hormone-independent phenotype of breast cancer cells. Cancer Res.56(14) , 3350–3358 (1996).
   PubMed Web of Science ®Google Scholar
• Digiovanna MP , ChuP, DavisonTLet al. Active signaling by HER-2/neu in a subpopulation of HER-2/neu-overexpressing ductal carcinoma in situ: clinicopathological correlates. Cancer Res. 62(22) , 6667–6673 (2002).
   PubMed Web of Science ®Google Scholar
• Oh AS , LorantLA, HollowayJN, MillerDL, KernFG, El-AshryD. Hyperactivation of MAPK induces loss of ERα expression in breast cancer cells. Mol. Endocrinol.15(8) , 1344–1359 (2001).
   PubMedGoogle Scholar
• Holloway JN , MurthyS, El-AshryD. A cytoplasmic substrate of mitogen-activated protein kinase is responsible for estrogen receptor-α down-regulation in breast cancer cells: the role of nuclear factor-κB. Mol. Endocrinol.18(6) , 1396–1410 (2004).
   PubMedGoogle Scholar
• Bayliss J , HilgerA, VishnuP, DiehlK, El-AshryD. Reversal of the estrogen receptor negative phenotype in breast cancer and restoration of antiestrogen response. Clin. Cancer Res.13(23) , 7029–7036 (2007).
   PubMed Web of Science ®Google Scholar
• Nakshatri H , Bhat-NakshatriP, MartinDA, GouletRJ Jr, Sledge GW Jr. Constitutive activation of NF-κB during progression of breast cancer to hormone-independent growth. Mol. Cell. Biol.17(7) , 3629–3639 (1997).
   PubMed Web of Science ®Google Scholar
• Adams BD , CoweeDM, WhiteBA. The role of miR-206 in the epidermal growth factor (EGF) induced repression of estrogen receptor-α (ERα) signaling and a luminal phenotype in MCF-7 breast cancer cells. Mol. Endocrinol.23(8) , 1215–1230 (2009).
   PubMed Web of Science ®Google Scholar
• Van Den Berg HW , LynchM, MartinJ, NelsonJ, DicksonGR, CrockardAD. Characterisation of a tamoxifen-resistant variant of the ZR-75–71 human breast cancer cell line (ZR-75–9a1) and ability of the resistant phenotype. Br. J. Cancer59(4) , 522–526 (1989).
   PubMed Web of Science ®Google Scholar
• Long B , MckibbenBM, LynchM, Van Den Berg HW. Changes in epidermal growth factor receptor expression and response to ligand associated with acquired tamoxifen resistance or oestrogen independence in the ZR-75-71 human breast cancer cell line. Br. J. Cancer65(6) , 865–869 (1992).
   PubMed Web of Science ®Google Scholar
• Encarnacion CA , CioccaDR, McguireWL, ClarkGM, FuquaSA, OsborneCK. Measurement of steroid hormone receptors in breast cancer patients on tamoxifen. Breast Cancer Res. Treat.26(3) , 237–246 (1993).
   PubMed Web of Science ®Google Scholar
• Johnston SR , Saccani-JottiG, SmithIEet al. Changes in estrogen receptor, progesterone receptor, and pS2 expression in tamoxifen-resistant human breast cancer. Cancer Res. 55(15) , 3331–3338 (1995).
   PubMed Web of Science ®Google Scholar
• Kuukasjarvi T , KononenJ, HelinH, HolliK, IsolaJ. Loss of estrogen receptor in recurrent breast cancer is associated with poor response to endocrine therapy. J. Clin. Oncol.14(9) , 2584–2589 (1996).
   PubMed Web of Science ®Google Scholar
• Gutierrez MC , DetreS, JohnstonSet al. Molecular changes in tamoxifen-resistant breast cancer: relationship between estrogen receptor, HER-2, and p38 mitogen-activated protein kinase. J. Clin.Oncol. 23(11) , 2469–2476 (2005).
   PubMed Web of Science ®Google Scholar
• Dworkin AM , HuangTH, TolandAE. Epigenetic alterations in the breast: implications for breast cancer detection, prognosis and treatment. Semin. Cancer. Biol.19(3) , 165–171 (2009).
   PubMed Web of Science ®Google Scholar
• Ellis MJ , TaoY, YoungOet al. Estrogen-independent proliferation is present in estrogen-receptor HER2-positive primary breast cancer after neoadjuvant letrozole. J. Clin. Oncol. 24(19) , 3019–3025 (2006).
   PubMed Web of Science ®Google Scholar
• Pettersson K , DelaunayF, GustafssonJA. Estrogen receptor β acts as a dominant regulator of estrogen signaling. Oncogene19(43) , 4970–4978 (2000).
   PubMed Web of Science ®Google Scholar
• Murphy LC , WatsonPH. Is oestrogen receptor-β a predictor of endocrine therapy responsiveness in human breast cancer? Endocr. Relat. Cancer13(2) , 327–334 (2006).
   PubMed Web of Science ®Google Scholar
• Paech K , WebbP, KuiperGGet al. Differential ligand activation of estrogen receptors ERα and ERβ at AP1 sites. Science 277(5331) , 1508–1510 (1997).
   PubMed Web of Science ®Google Scholar
• Honma N , HoriiR, IwaseTet al. Clinical importance of estrogen receptor-β evaluation in breast cancer patients treated with adjuvant tamoxifen therapy. J. Clin. Oncol. 26(22) , 3727–3734 (2008).
   PubMed Web of Science ®Google Scholar
• Nair HB , KirmaNB, GanapathyM, VadlamudiRK, TekmalRR. Estrogen receptor-β activation in combination with letrozole blocks the growth of breast cancer tumors resistant to letrozole therapy. Steroids76(8) , 792–796 (2011).
   PubMed Web of Science ®Google Scholar
• Chang HG , KimSJ, ChungKWet al. Tamoxifen-resistant breast cancers show less frequent methylation of the estrogen receptor β but not the estrogen receptor α gene. J. Mol. Med. 83(2) , 132–139 (2005).
   PubMed Web of Science ®Google Scholar
• Speirs V , MaloneC, WaltonDS, KerinMJ, AtkinSL. Increased expression of estrogen receptor β mRNA in tamoxifen-resistant breast cancer patients. Cancer Res.59(21) , 5421–5424 (1999).
   PubMed Web of Science ®Google Scholar
• Jensen EV , ChengG, PalmieriCet al. Estrogen receptors and proliferation markers in primary and recurrent breast cancer. Proc. Natl Acad. Sci. USA 98(26) , 15197–15202 (2001).
   PubMed Web of Science ®Google Scholar
• Klinge CM , RiggsKA, WickramasingheNSet al. Estrogen receptor α 46 is reduced in tamoxifen resistant breast cancer cells and re-expression inhibits cell proliferation and estrogen receptor α 66-regulated target gene transcription. Mol. Cell. Endocrinol. 323(2) , 268–276 (2010).
   PubMed Web of Science ®Google Scholar
• Lin SL , YanLY, ZhangXTet al. ER-α36, a variant of ER-α, promotes tamoxifen agonist action in endometrial cancer cells via the MAPK/ERK and PI3K/Akt pathways. PLoS ONE 5(2) , e9013 (2010).
   PubMed Web of Science ®Google Scholar
• Luco RF , AlloM, SchorIE, KornblihttAR, MisteliT. Epigenetics in alternative pre-mRNA splicing. Cell144(1) , 16–26 (2011).
   PubMed Web of Science ®Google Scholar
• Zhou Y , YauC, GrayJWet al. Enhanced NF κ B and AP-1 transcriptional activity associated with antiestrogen resistant breast cancer. BMC Cancer 7 , 59 (2007).
   PubMed Web of Science ®Google Scholar
• Osborne CK , BardouV, HoppTAet al. Role of the estrogen receptor coactivator AIB1 (SRC-3) and HER-2/neu in tamoxifen resistance in breast cancer. J. Natl Cancer Inst. 95(5) , 353–361 (2003).
   PubMedGoogle Scholar
• Fleming FJ , MyersE, KellyGet al. Expression of SRC-1, AIB1, and PEA3 in HER2 mediated endocrine resistant breast cancer; a predictive role for SRC-1. J. Clin. Pathol. 57(10) , 1069–1074 (2004).
   PubMed Web of Science ®Google Scholar
• Mann M , CortezV, VadlamudiRK. Epigenetics of estrogen receptor signaling: role in hormonal cancer progression and therapy. Cancers3(2) , 1691–1707 (2011).
   PubMedGoogle Scholar
• Lavinsky RM , JepsenK, HeinzelTet al. Diverse signaling pathways modulate nuclear receptor recruitment of N-CoR and SMRT complexes. Proc. Natl Acad. Sci. USA 95(6) , 2920–2925 (1998).
   PubMed Web of Science ®Google Scholar
• Benz CC , ScottGK, SarupJCet al. Estrogen-dependent, tamoxifen-resistant tumorigenic growth of MCF-7 cells transfected with HER2/neu. Breast Cancer Res. Treat. 24(2) , 85–95 (1993).
   Web of Science ®Google Scholar
• Knowlden JM , HutchesonIR, JonesHEet al. Elevated levels of epidermal growth factor receptor/c-erbB2 heterodimers mediate an autocrine growth regulatory pathway in tamoxifen-resistant MCF-7 cells. Endocrinology 144(3) , 1032–1044 (2003).
   PubMed Web of Science ®Google Scholar
• Stal O , BorgA, FernoM, KallstromAC, MalmstromP, NordenskjoldB. ErbB2 status and the benefit from two or five years of adjuvant tamoxifen in postmenopausal early stage breast cancer. Ann. Oncol.11(12) , 1545–1550 (2000).
   PubMed Web of Science ®Google Scholar
• De Laurentiis M , ArpinoG, MassarelliEet al. A meta-analysis on the interaction between HER-2 expression and response to endocrine treatment in advanced breast cancer. Clin. Cancer Res. 11(13) , 4741–4748 (2005).
   PubMed Web of Science ®Google Scholar
• Romond EH , PerezEA, BryantJet al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N. Engl. J. Med. 353(16) , 1673–1684 (2005).
   PubMed Web of Science ®Google Scholar
• Pietras RJ , Marquez-GarbanDC. Membrane-associated estrogen receptor signaling pathways in human cancers. Clin. Cancer Res.13(16) , 4672–4676 (2007).
   PubMed Web of Science ®Google Scholar
• Fan P , WangJ, SantenRJ, YueW. Long-term treatment with tamoxifen facilitates translocation of estrogen receptor α out of the nucleus and enhances its interaction with EGFR in MCF-7 breast cancer cells. Cancer Res.67(3) , 1352–1360 (2007).
   PubMed Web of Science ®Google Scholar
• Yang Z , BarnesCJ, KumarR. Human epidermal growth factor receptor 2 status modulates subcellular localization of and interaction with estrogen receptor α in breast cancer cells. Clin. Cancer Res.10(11) , 3621–3628 (2004).
   PubMed Web of Science ®Google Scholar
• Chung YL , SheuML, YangSC, LinCH, YenSH. Resistance to tamoxifen-induced apoptosis is associated with direct interaction between Her2/neu and cell membrane estrogen receptor in breast cancer. Int. J. Cancer97(3) , 306–312 (2002).
   PubMed Web of Science ®Google Scholar
• Chong K , SubramanianA, SharmaA, MokbelK. Measuring IGF-1, ER-α and EGFR expression can predict tamoxifen-resistance in ER-positive breast cancer. Anticancer Res.31(1) , 23–32 (2011).
   PubMed Web of Science ®Google Scholar
• Skliris GP , NugentZJ, RowanBG, PennerCR, WatsonPH, MurphyLC. A phosphorylation code for oestrogen receptor-α predicts clinical outcome to endocrine therapy in breast cancer. Endocr. Relat. Cancer17(3) , 589–597 (2010).
   PubMed Web of Science ®Google Scholar
• Murphy LC , SeekalluSV, WatsonPH. Clinical significance of estrogen receptor phosphorylation. Endocr. Relat. Cancer18(1) , R1–R14 (2011).
   PubMed Web of Science ®Google Scholar
• Allen KE , WeissGJ. Resistance may not be futile: microRNA biomarkers for chemoresistance and potential therapeutics. Mol. Cancer Ther.9(12) , 3126–3136 (2010).
   PubMed Web of Science ®Google Scholar
• Miller TE , GhoshalK, RamaswamyBet al. MicroRNA-221/222 confers tamoxifen resistance in breast cancer by targeting p27Kip1. J. Biol. Chem. 283(44) , 29897–29903 (2008).
   PubMed Web of Science ®Google Scholar
• Rao X , Di Leva G, Li M et al. MicroRNA-221/222 confers breast cancer fulvestrant resistance by regulating multiple signaling pathways. Oncogene30(9) , 1082–1097 (2011).
   PubMed Web of Science ®Google Scholar
• Kim SJ , KangHS, JungSYet al. Methylation patterns of genes coding for drug-metabolizing enzymes in tamoxifen-resistant breast cancer tissues. J. Mol. Med. 88(11) , 1123–1131 (2010).
   PubMed Web of Science ®Google Scholar
• Khan S , KumagaiT, VoraJet al.PTEN promoter is methylated in a proportion of invasive breast cancers. Int. J. Cancer112(3) , 407–410 (2004).
   PubMed Web of Science ®Google Scholar
• Shoman N , KlassenS, McfaddenA, BickisMG, TorlakovicE, ChibbarR. Reduced PTEN expression predicts relapse in patients with breast carcinoma treated by tamoxifen. Modern Pathol.18(2) , 250–259 (2005).
   PubMed Web of Science ®Google Scholar
• Phuong NT , KimSK, LimSCet al. Role of PTEN promoter methylation in tamoxifen-resistant breast cancer cells. Breast Cancer Res. Treat. DOI: 10.1007/s10549-010-1304-2 (2010).
   PubMed Web of Science ®Google Scholar
• Waltersson MA , AskmalmMS, NordenskjoldB, FornanderT, SkoogL, StalO. Altered expression of cyclin E and the retinoblastoma protein influences the effect of adjuvant therapy in breast cancer. Int. J. Oncol.34(2) , 441–448 (2009).
   PubMed Web of Science ®Google Scholar
• Butt AJ , McneilCM, MusgroveEA, SutherlandRL. Downstream targets of growth factor and oestrogen signalling and endocrine resistance: the potential roles of c-Myc, cyclin D1 and cyclin E. Endocr. Relat. Cancer12(Suppl. 1) , S47–S59 (2005).
   PubMed Web of Science ®Google Scholar
• Miller TW , BalkoJM, GhazouiZet al. A gene expression signature from human breast cancer cells with acquired hormone independence identifies MYC as a mediator of antiestrogen resistance. Clin. Cancer Res. 17(7) , 2024–2034 (2011).
   PubMed Web of Science ®Google Scholar
• Barone I , BruscoL, GuGet al. Loss of Rho GDIα and resistance to tamoxifen via effects on estrogen receptor α. J. Natl Cancer Inst. 103(7) , 538–552 (2011).
   PubMedGoogle Scholar
• Leu YW , YanPS, FanMet al. Loss of estrogen receptor signaling triggers epigenetic silencing of downstream targets in breast cancer. Cancer Res. 64(22) , 8184–8192 (2004).
   PubMed Web of Science ®Google Scholar
• Murphy LC , LeygueE, NiuY, SnellL, HoSM, WatsonPH. Relationship of coregulator and oestrogen receptor isoform expression to de novo tamoxifen resistance in human breast cancer. Br. J. Cancer87(12) , 1411–1416 (2002).
   PubMed Web of Science ®Google Scholar
• Shi L , DongB, LiZet al. Expression of ER-{α}36, a novel variant of estrogen receptor {α}, and resistance to tamoxifen treatment in breast cancer. J. Clin. Oncol. 27(21) , 3423–3429 (2009).
   PubMed Web of Science ®Google Scholar
• Shou J , MassarwehS, OsborneCKet al. Mechanisms of tamoxifen resistance: increased estrogen receptor-HER2/neu cross-talk in ER/HER2-positive breast cancer. J. Natl Cancer Inst. 96(12) , 926–935 (2004).
   PubMedGoogle Scholar
• Ferguson AT , LapidusRG, BaylinSB, DavidsonNE. Demethylation of the estrogen receptor gene in estrogen receptor-negative breast cancer cells can reactivate estrogen receptor gene expression. Cancer Res.55(11) , 2279–2283 (1995).
   PubMed Web of Science ®Google Scholar
• Yang X , FergusonAT, NassSJet al. Transcriptional activation of estrogen receptor α in human breast cancer cells by histone deacetylase inhibition. Cancer Res. 60(24) , 6890–6894 (2000).
   PubMed Web of Science ®Google Scholar
• Bovenzi V , MomparlerRL. Antineoplastic action of 5-aza-2´-deoxycytidine and histone deacetylase inhibitor and their effect on the expression of retinoic acid receptor β and estrogen receptor α genes in breast carcinoma cells. Cancer Chemother. Pharmacol.48(1) , 71–76 (2001).
   PubMed Web of Science ®Google Scholar
• Yang X , PhillipsDL, FergusonAT, NelsonWG, HermanJG, DavidsonNE. Synergistic activation of functional estrogen receptor (ER)-α by DNA methyltransferase and histone deacetylase inhibition in human ER-α-negative breast cancer cells. Cancer Res.61(19) , 7025–7029 (2001).
   PubMed Web of Science ®Google Scholar
• Keen JC , YanL, MackKMet al. A novel histone deacetylase inhibitor, scriptaid, enhances expression of functional estrogen receptor α (ER) in ER negative human breast cancer cells in combination with 5-aza 2´-deoxycytidine. Breast Cancer Res. Treat. 81(3) , 177–186 (2003).
   PubMed Web of Science ®Google Scholar
• Zhou Q , AtadjaP, DavidsonNE. Histone deacetylase inhibitor LBH589 reactivates silenced estrogen receptor α (ER) gene expression without loss of DNA hypermethylation. Cancer Biol. Ther.6(1) , 64–69 (2007).
   PubMed Web of Science ®Google Scholar
• Fan J , YinWJ, LuJSet al. ER α negative breast cancer cells restore response to endocrine therapy by combination treatment with both HDAC inhibitor and DNMT inhibitor. J. Cancer Res. Clin. Oncol. 134(8) , 883–890 (2008).
   PubMed Web of Science ®Google Scholar
• Travaglini L , VianL, BilliM, GrignaniF, NerviC. Epigenetic reprogramming of breast cancer cells by valproic acid occurs regardless of estrogen receptor status. Int. J. Biochem. Cell. Biol.41(1) , 225–234 (2009).
   PubMed Web of Science ®Google Scholar
• Scott GK , MardenC, XuF, KirkL, BenzCC. Transcriptional repression of ErbB2 by histone deacetylase inhibitors detected by a genomically integrated ErbB2 promoter-reporting cell screen. Mol. Cancer Ther.1(6) , 385–392 (2002).
   PubMed Web of Science ®Google Scholar
• Bruzzese F , LeoneA, RoccoMet al. HDAC inhibitor vorinostat enhances the antitumor effect of gefitinib in squamous cell carcinoma of head and neck by modulating ErbB receptor expression and reverting EMT. J. Cell. Physiol. 226(9) , 2378–2390 (2011).
   PubMed Web of Science ®Google Scholar
• Wedel S , HudakL, SeibelJMet al. Inhibitory effects of the HDAC inhibitor valproic acid on prostate cancer growth are enhanced by simultaneous application of the mTOR inhibitor RAD001. Life Sci. 88(9–10) , 418–424 (2011).
   PubMed Web of Science ®Google Scholar
• Chou CW , WuMS, HuangWC, ChenCC. HDAC inhibition decreases the expression of EGFR in colorectal cancer cells. PLoS ONE6(3) , e18087 (2011).
   PubMedGoogle Scholar
• Drummond DC , MarxC, GuoZet al. Enhanced pharmacodynamic and antitumor properties of a histone deacetylase inhibitor encapsulated in liposomes or ErbB2-targeted immunoliposomes. Clin. Cancer Res. 11(9) , 3392–3401 (2005).
   PubMed Web of Science ®Google Scholar
• Scott GK , MarxC, BergerCEet al. Destabilization of ERBB2 transcripts by targeting 3´ untranslated region messenger RNA associated HuR and histone deacetylase-6. Mol. Cancer Res. 6(7) , 1250–1258 (2008).
   PubMed Web of Science ®Google Scholar
• Zhou Q , ShawPG, DavidsonNE. Inhibition of histone deacetylase suppresses EGF signaling pathways by destabilizing EGFR mRNA in ER-negative human breast cancer cells. Breast Cancer Res. Treat.117(2) , 443–451 (2009).
   PubMed Web of Science ®Google Scholar
• Reid G , HubnerMR, MetivierRet al. Cyclic, proteasome-mediated turnover of unliganded and liganded ERα on responsive promoters is an integral feature of estrogen signaling. Mol. Cell 11(3) , 695–707 (2003).
   PubMed Web of Science ®Google Scholar
• Reid G , MetivierR, LinCYet al. Multiple mechanisms induce transcriptional silencing of a subset of genes, including oestrogen receptor α, in response to deacetylase inhibition by valproic acid and trichostatin A. Oncogene 24(31) , 4894–4907 (2005).
   PubMed Web of Science ®Google Scholar
• Bicaku E , MarchionDC, SchmittM, MunsterPN. Selective inhibition of histone deacetylase 2 silences progesterone receptor mediated signaling. Cancer Res.68(5) , 1513–1519 (2008).
   PubMed Web of Science ®Google Scholar
• Hodges-Gallagher L , ValentineCD, BaderSE, KushnerPJ. Inhibition of histone deacetylase enhances the anti-proliferative action of antiestrogens on breast cancer cells and blocks tamoxifen-induced proliferation of uterine cells. Breast Cancer Res. Treat.105(3) , 297–309 (2007).
   PubMed Web of Science ®Google Scholar
• Hirokawa Y , ArnoldM, NakajimaH, ZalcbergJ, MarutaH. Signal therapy of breast cancers by the HDAC inhibitor FK228 that blocks the activation of PAK1 and abrogates the tamoxifen-resistance. Cancer Biol. Ther.4(9) , 956–960, (2005).
   PubMed Web of Science ®Google Scholar
• Thomas S , ThurnKT, BicakuE, MarchionDC, MunsterPN. Addition of a histone deacetylase inhibitor redirects tamoxifen-treated breast cancer cells into apoptosis, which is opposed by the induction of autophagy. Breast Cancer Res. Treat. DOI: 10.1007/s10549-011-1364-y (2011) (Epub ahead of print).
   Google Scholar
• Zuo T , LiuTM, LanXet al. Epigenetic silencing mediated through activated PI3K/AKT signaling in breast cancer. Cancer Res. 71(5) , 1752–1762 (2011).
   PubMed Web of Science ®Google Scholar
• Fuino L , BaliP, WittmannSet al. Histone deacetylase inhibitor LAQ824 down-regulates Her-2 and sensitizes human breast cancer cells to trastuzumab, taxotere, gemcitabine, and epothilone B. Mol. Cancer Ther. 2(10) , 971–984 (2003).
   PubMed Web of Science ®Google Scholar
• Campone M , ConteP, AmadoriDet al. Phase I trial of panobinostat (LBH589) in combination with trastuzumab in pretreated HER2-positive metastatic breast cancer (mBC): preliminary safety, efficacy and pharmacokinetic results. Cancer Res. 69(Suppl. 24) , 6101–6101 (2010).
   Web of Science ®Google Scholar
• Fan M , YanPS, Hartman-FreyCet al. Diverse gene expression and DNA methylation profiles correlate with differential adaptation of breast cancer cells to the antiestrogens tamoxifen and fulvestrant. Cancer Res. 66(24) , 11954–11966 (2006).
   PubMed Web of Science ®Google Scholar
• Rodriguez BA , ChengAS, YanPSet al. Epigenetic repression of the estrogen-regulated homeobox B13 gene in breast cancer. Carcinogenesis 29(7) , 1459–1465 (2008).
   PubMed Web of Science ®Google Scholar
• Okuda H , ToyotaM, IshidaWet al. Epigenetic inactivation of the candidate tumor suppressor gene HOXB13 in human renal cell carcinoma. Oncogene 25(12) , 1733–1742 (2006).
   PubMed Web of Science ®Google Scholar
• Muthusamy V , DuraisamyS, BradburyCMet al. Epigenetic silencing of novel tumor suppressors in malignant melanoma. Cancer Res. 66(23) , 11187–11193 (2006).
   PubMed Web of Science ®Google Scholar
• Iorns E , TurnerNC, ElliottRet al. Identification of CDK10 as an important determinant of resistance to endocrine therapy for breast cancer. Cancer Cell 13(2) , 91–104 (2008).
   PubMed Web of Science ®Google Scholar
• Munster PN , ThurnKT, ThomasSet al. A Phase II study of the histone deacetylase inhibitor vorinostat combined with tamoxifen for the treatment of patients with hormone therapy-resistant breast cancer. Br. J. Cancer 104(12) , 1828–1835 (2011).
   PubMed Web of Science ®Google Scholar

▪ Websites

• National comprehensive cancer network. Clinical practice guidelines in oncology – breast cancer (2011) www.nccn.gov
   Google Scholar
• Clinical trials registry www.clinicaltrials.gov
   Google Scholar
• Azacitidine in Treating Patients With Triple Negative Stage I–IV Invasive Breast Cancer That Can Be Removed By Surgery http://clinicaltrials.gov/ct2/show/NCT01292083
   Google Scholar
• Entinostat and Anastrozole in Treating Postmenopausal Women With Triple-Negative Breast Cancer That Can Be Removed by Surgery http://clinicaltrials.gov/ct2/show/NCT01234532
   Google Scholar
• Re-expression of ER in Triple Negative Breast Cancers http://clinicaltrials.gov/ct2/show/NCT01194908
   Google Scholar
• A Phase II, Multicenter Study of the Effect of the Addition of SNDX-275 to Continued Aromatase Inhibitor (AI) Therapy in Postmenopausal Women With ER+ Breast Cancer Whose Disease is Progressing http://clinicaltrials.gov/ct2/show/NCT00828854
   Google Scholar
• Study to Evaluate Exemestane With and Without SNDX-275 in Treatment of Postmenopausal Women With Advanced Breast Cancer http://clinicaltrials.gov/ct2/show/NCT00676663
   Google Scholar
• Vorinostat in Treating Patients With Stage IV Breast Cancer Receiving Aromatase Inhibitor Therapy http://clinicaltrials.gov/ct2/show/NCT01153672
   Google Scholar
• Phase II Trial of SAHA and Tamoxifen for Patients With Breast Cancer http://clinicaltrials.gov/ct2/show/NCT00365599
   Google Scholar