New and developing chemical pharmacotherapy for treating hormone receptor-positive/HER2-negative breast cancer

References

• Visovsky C. Treatment considerations for the management of patients with hormone receptor-positive metastatic breast cancer. J Adv Pract Oncol. 2014;5(5):321–330.
   PubMedGoogle Scholar
• Rugo HS, Rumble RB, Macrae E, et al. Endocrine therapy for hormone receptor-positive metastatic breast cancer: american society of clinical oncology guideline. J Clin Oncol. 2016;34(25):3069–3103.
   Web of Science ®Google Scholar
• Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;365(9472):1687–1717.
   PubMed Web of Science ®Google Scholar
• Dowsett M, Forbes JF, Bradley R, et al. Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials. Lancet. 2015;386(10001):1341–1352.
   PubMed Web of Science ®Google Scholar
• Pagani O, Regan MM, Walley BA, et al. Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. N Engl J Med. 2014;371(2):107–118.
   PubMed Web of Science ®Google Scholar
• Francis PA, Regan MM, Fleming GF, et al. Adjuvant ovarian suppression in premenopausal breast cancer. N Engl J Med. 2015;372(5):436–446.
   PubMed Web of Science ®Google Scholar
• Gonzalez-Angulo AM, Morales-Vasquez F, Hortobagyi GN. Overview of resistance to systemic therapy in patients with breast cancer. Adv Exp Med Biol. 2007;608:1–22.
   PubMed Web of Science ®Google Scholar
• Inc NCCN. NCCN practice guidelines in oncology. Breast cancer. Version 2.2016. Available from: https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf.
   Google Scholar
• Osborne CK, Schiff R. Mechanisms of endocrine resistance in breast cancer. Annu Rev Med. 2011;62:233–247.
   PubMed Web of Science ®Google Scholar
• Musgrove EA, Sutherland RL. Biological determinants of endocrine resistance in breast cancer. Nat Rev Cancer. 2009;9(9):631–643.
   PubMed Web of Science ®Google Scholar
• Rossi V, Sarotto I, Maggiorotto F, et al. Moderate immunohistochemical expression of HER-2 (2+) without HER-2 gene amplification is a negative prognostic factor in early breast cancer. Oncologist. 2012;17(11):1418–1425.
   PubMed Web of Science ®Google Scholar
• Robinson DR, Wu YM, Vats P, et al. Activating ESR1 mutations in hormone-resistant metastatic breast cancer. Nat Genet. 2013;45(12):1446–1451.
   PubMed Web of Science ®Google Scholar
• Toy W, Shen Y, Won H, et al. ESR1 ligand-binding domain mutations in hormone-resistant breast cancer. Nat Genet. 2013;45(12):1439–1445.
   PubMed Web of Science ®Google Scholar
• Jeselsohn R, Yelensky R, Buchwalter G, et al. Emergence of constitutively active estrogen receptor-alpha mutations in pretreated advanced estrogen receptor-positive breast cancer. Clin Cancer Res. 2014;20(7):1757–1767.
   PubMed Web of Science ®Google Scholar
• Fribbens C, O’Leary B, Kilburn L, et al. Plasma ESR1 mutations and the treatment of estrogen receptor-positive advanced breast cancer. J Clin Oncol. 2016;34(25):2961–2968.
   PubMed Web of Science ®Google Scholar
• Baselga J, Campone M, Piccart M, et al. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med. 2012;366(6):520–529.
   PubMed Web of Science ®Google Scholar
• Bachelot T, Bourgier C, Cropet C, et al. Randomized phase II trial of everolimus in combination with tamoxifen in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer with prior exposure to aromatase inhibitors: a GINECO study. J Clin Oncol. 2012;30(22):2718–2724.
   PubMed Web of Science ®Google Scholar
• Wolff AC, Lazar AA, Bondarenko I, et al. Randomized phase III placebo-controlled trial of letrozole plus oral temsirolimus as first-line endocrine therapy in postmenopausal women with locally advanced or metastatic breast cancer. J Clin Oncol. 2013;31(2):195–202.
   PubMed Web of Science ®Google Scholar
• Piccart M, Hortobagyi GN, Campone M, et al. Everolimus plus exemestane for hormone-receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: overall survival results from BOLERO-2†. Ann Oncol. 2014;25(12):2357–2362.
   PubMed Web of Science ®Google Scholar
• Dickler MN, Barry WT, Cirrincione CT, et al. Phase III trial evaluating the addition of bevacizumab to letrozole as first-line endocrine therapy for treatment of hormone-receptor positive advanced breast cancer: CALGB 40503 (Alliance). J Clin Oncol. 2015; 33( suppl;abstr 501).
   Web of Science ®Google Scholar
• Martin M, Loibl S, von Minckwitz G, et al. Phase III trial evaluating the addition of bevacizumab to endocrine therapy as first-line treatment for advanced breast cancer: the letrozole/fulvestrant and avastin (LEA) study. J Clin Oncol. 2015;33(9):1045–1052.
   PubMed Web of Science ®Google Scholar
• De Jong RS, Sonke GS, Maass N, et al. Fulvestrant (FUL) plus enzastaurin(ENZA) vs FUL plus placebo (PBO) in aromatase inhibitor(AI)-resistant metastatic breast cancer (MBC): a randomized, double-blind, phase 2 trial. Ann Oncol. 2013;23:124.
   Web of Science ®Google Scholar
• Hyams DM, Chan A, de Oliveira C, et al. Cediranib in combination with fulvestrant in hormone-sensitive metastatic breast cancer: a randomized Phase II study. Invest New Drugs. 2013;31(5):1345–1354.
   PubMed Web of Science ®Google Scholar
• Carlson RW, O'Neill A, Vidaurre T, et al. A randomized trial of combination anastrozole plus gefitinib and of combination fulvestrant plus gefitinib in the treatment of postmenopausal women with hormone receptor positive metastatic breast cancer. Breast Cancer Res Treat. 2012;133(3):1049–1056.
   PubMed Web of Science ®Google Scholar
• Cristofanilli M, Valero V, Mangalik A, et al. Phase II, randomized trial to compare anastrozole combined with gefitinib or placebo in postmenopausal women with hormone receptor-positive metastatic breast cancer. Clin Cancer Res. 2010;16(6):1904–1914.
   PubMed Web of Science ®Google Scholar
• Osborne CK, Neven P, Dirix LY, et al. Gefitinib or placebo in combination with tamoxifen in patients with hormone receptor-positive metastatic breast cancer: a randomized phase II study. Clin Cancer Res. 2011;17(5):1147–1159.
   PubMed Web of Science ®Google Scholar
• Burstein HJ, Cirrincione CT, Barry WT, et al. Endocrine therapy with or without inhibition of epidermal growth factor receptor and human epidermal growth factor receptor 2: a randomized, double-blind, placebo-controlled phase III trial of fulvestrant with or without lapatinib for postmenopausal women with hormone receptor-positive advanced breast cancer-CALGB 40302 (Alliance). J Clin Oncol. 2014;32(35):3959–3966.
   PubMed Web of Science ®Google Scholar
• Ryan P, Neven P, Blackwell K, et al. P1-17-01: Figitumumab Plus Exemestane Versus Exemestane as First-Line Treatment of Postmenopausal Hormone Receptor-Positive Advanced Breast Cancer: A Randomized, Open-Label Phase II Trial. Cancer Res Dec. 2011;71(24Supplement): P1-17-01.
   Google Scholar
• Robertson JF, Ferrero JM, Bourgeois H, et al. Ganitumab with either exemestane or fulvestrant for postmenopausal women with advanced, hormone-receptor-positive breast cancer: a randomised, controlled, double-blind, phase 2 trial. Lancet Oncol. 2013;14(3):228–235.
   PubMed Web of Science ®Google Scholar
• Rugo HS, Tredan O, Ro J, et al. Results from the phase 2 trial of ridaforolimus, dalotuzumab, and exemestane compared to ridaforolimus and exemestane in advanced breast cancer. Cancer Res. 2015;75:PD5–1.
   Google Scholar
• Shapiro GI. Cyclin-dependent kinase pathways as targets for cancer treatment. J Clin Oncol. 2006;24(11):1770–1783.
   PubMed Web of Science ®Google Scholar
• Grossel MJ, Hinds PW. From cell cycle to differentiation: an expanding role for cdk6. Cell Cycle. 2006;5(3):266–270.
   PubMed Web of Science ®Google Scholar
• Lange CA, Yee D. Killing the second messenger: targeting loss of cell cycle control in endocrine-resistant breast cancer. Endocr Relat Cancer. 2011;18(4):C19–24.
   PubMed Web of Science ®Google Scholar
• Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature. 2012; 490(7418): 61–70.
   PubMed Web of Science ®Google Scholar
• Musgrove EA, Caldon CE, Barraclough J, et al. Cyclin D as a therapeutic target in cancer. Nat Rev Cancer. 2011;11(8):558–572.
   PubMed Web of Science ®Google Scholar
• Geradts J, Wilson PA. High frequency of aberrant p16(INK4A) expression in human breast cancer. Am J Pathol. 1996;149(1):15–20.
   PubMed Web of Science ®Google Scholar
• Fry DW, Harvey PJ, Keller PR, et al. Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts. Mol Cancer Ther. 2004;3(11):1427–1438.
   PubMed Web of Science ®Google Scholar
• Finn RS, Dering J, Conklin D, et al. PD 0332991, a selective cyclin D kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro. Breast Cancer Res. 2009;11(5):R77.
   PubMed Web of Science ®Google Scholar
• Flaherty KT, Lorusso PM, Demichele A, et al. Phase I, dose-escalation trial of the oral cyclin-dependent kinase 4/6 inhibitor PD 0332991, administered using a 21-day schedule in patients with advanced cancer. Clin Cancer Res. 2012;18(2):568–576.
   PubMed Web of Science ®Google Scholar
• Schwartz GK, LoRusso PM, Dickson MA, et al. Phase I study of PD 0332991, a cyclin-dependent kinase inhibitor, administered in 3-week cycles (Schedule 2/1). Br J Cancer. 2011;104(12):1862–1868.
   PubMed Web of Science ®Google Scholar
• Slamon DJH, Hurvitz S, Applebaum S, et al. Phase I study of PD 0332991, cyclin-D kinase (CDK) 4/6 inhibitor in combination with letrozole for first-line treatment of patients with ER-positive, HER2-negative breast cancer. J Clin Oncol. 2010;28:15s(suppl; abstr 3060).
   Google Scholar
• Finn RS, Crown JP, Lang I, et al. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol. 2015;16(1):25–35.
   PubMed Web of Science ®Google Scholar
• Finn RS, Martin M, Rugo HS, et al. PALOMA-2: primary results from a phase III trial of palbociclib (P) with letrozole (L) compared with letrozole alone in postmenopausal women with ER+/HER2– advanced breast cancer (ABC). J Clin Oncol. 2016;34(suppl; abstr 507).
   Google Scholar
• Cristofanilli M, Turner NC, Bondarenko I, et al. Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial. Lancet Oncol. 2016;17(4):425–439.
   Web of Science ®Google Scholar
• Mayer EL, Gropper AB, Tung NM, et al. Adjuvant palbociclib (P) plus endocrine therapy (ET) for hormone receptor positive (HR+) breast cancer: a phase II feasibility study. J Clin Oncol. 2014;32:5s(suppl; abstr TPS654).
   Web of Science ®Google Scholar
• Sherr CJ, Beach D, Shapiro GI. Targeting CDK4 and CDK6: from discovery to therapy. Cancer Discov. 2016;6(4):353–367.
   PubMed Web of Science ®Google Scholar
• Rader J, Russell MR, Hart LS, et al. Dual CDK4/CDK6 inhibition induces cell-cycle arrest and senescence in neuroblastoma. Clin Cancer Res. 2013;19(22):6173–6182.
   PubMed Web of Science ®Google Scholar
• Zhang Y-X, Sicinska E, Czaplinski JT, et al. Antiproliferative effects of CDK4/6 inhibition in CDK4-amplified human liposarcoma in vitro and in vivo. Mol Cancer Ther. 2014;13(9):2184–2193.
   PubMed Web of Science ®Google Scholar
• Infante JR, Shapiro GI, Witteveen PO, et al. Abstract A276: phase 1 multicenter, open label, dose-escalation study of LEE011, an oral inhibitor of cyclin-dependent kinase 4/6, in patients with advanced solid tumors or lymphomas. Mol Cancer Ther. 2013;12(11 Supplement):A276–A276.
   Google Scholar
• Juric D, Munster PN, Campone M, et al. Ribociclib (LEE011) and letrozole in estrogen receptor-positive (ER+), HER2-negative (HER2–) advanced breast cancer (aBC): phase Ib safety, preliminary efficacy and molecular analysis. J Clin Oncol. 2016; 34(suppl;abstr 568).
   Google Scholar
• Fasching PA, Jerusalem GHM, Pivot X, et al. Phase III study of ribociclib (LEE011) plus fulvestrant for the treatment of postmenopausal patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (aBC) who have received no or only one line of prior endocrine treatment (ET): MONALEESA-3. J Clin Oncol. 2016;34(suppl;abstr TPS624).
   PubMed Web of Science ®Google Scholar
• Bardia A, Modi S, Chavez-Mac Gregor M, et al. PhaseIb/II study of LEE011, everolimus, and exemestane in postmenopausal women withER+/HER2-metastatic breast cancer. J Clin Oncol. 2014;32:5s(suppl;abstr 535).
   PubMed Web of Science ®Google Scholar
• Vora SR, Juric D, Kim N, et al. CDK 4/6 inhibitors sensitize PIK3CA mutant breast cancer to PI3K inhibitors. Cancer Cell. 2014;26(1):136–149.
   PubMed Web of Science ®Google Scholar
• Juric D, Hamilton E, Garcia Estévez L, et al. Abstract P5-19-24: phase Ib/II study of LEE011 and BYL719 and letrozole in ER+, HER2– breast cancer: safety, preliminary efficacy and molecular analysis. Cancer Res. 2015;75(9Supplement):P5-19-24-P15-19-24.
   Google Scholar
• Gelbert LM, Cai S, Lin X, et al. Preclinical characterization of the CDK4/6 inhibitor LY2835219: in-vivo cell cycle-dependent/independent anti-tumor activities alone/in combination with gemcitabine. Invest New Drugs. 2014;32(5):825–837.
   PubMed Web of Science ®Google Scholar
• Patnaik A, Rosen LS, Tolaney SM, et al. Efficacy and safety of abemaciclib, an inhibitor of CDK4 and CDK6, for patients with breast cancer, non-small cell lung cancer, and other solid tumors. Cancer Discov. 2016;6(7):740–753.
   PubMed Web of Science ®Google Scholar
• Goetz MP, Beeram M, Beck T, et al. Abstract P4-13-25: Abemaciclib, an inhibitor of CDK4 and CDK6, combined with endocrine and HER2-targeted therapies for women with metastatic breast cancer. Cancer Res. 2016;76(4 Supplement):PP4–25.
   Google Scholar
• Dickler MN, Tolaney SM, Rugo HS, et al. MONARCH1: results from a phase II study of abemaciclib, a CDK4 and CDK6 inhibitor, as monotherapy, in patients with HR+/HER2- breast cancer, after chemotherapy for advanced disease. J Clin Oncol. 2016; 34(suppl;abstr 510).
   Google Scholar
• Raub TJ, Wishart GN, Kulanthaivel P, et al. Brain exposure of two selective dual CDK4 and CDK6 inhibitors and the antitumor activity of CDK4 and CDK6 inhibition in combination with temozolomide in an intracranial glioblastoma xenograft. Drug Metab Dispos. 2015;43(9):1360–1371.
   PubMed Web of Science ®Google Scholar
• Llombart A, Toi M, Klise SR, et al. Abstract OT1-1-07: A phase III study of abemaciclib (LY2835219) combined with fulvestrant in women with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) breast cancer (MONARCH 2). Cancer Res. 2015;75(9 Supplement):OT1–07.
   Google Scholar
• Goetz MP, Toi M, Klise S, et al. MONARCH 3: A randomized phase III study of anastrozole or letrozole plus abemaciclib, a CDK4/6 inhibitor, or placebo in first-line treatment of women with HR+, HER2-locoregionally recurrent or metastatic breast cancer (MBC). J Clin Oncol. 2015;33(suppl;abstr TPS624).
   PubMed Web of Science ®Google Scholar
• Geuna E, Milani A, Martinello R, et al. Buparlisib, an oral pan-PI3K inhibitor for the treatment of breast cancer. Expert Opin Investig Drugs. 2015;24(3):421–431.
   PubMed Web of Science ®Google Scholar
• Thorpe LM, Yuzugullu H, Zhao JJ. PI3K in cancer: divergent roles of isoforms, modes of activation and therapeutic targeting. Nat Rev Cancer. 2015;15(1):7–24.
   PubMed Web of Science ®Google Scholar
• Bachman KE, Argani P, Samuels Y, et al. The PIK3CA gene is mutated with high frequency in human breast cancers. Cancer Biol Ther. 2004;3(8):772–775.
   PubMed Web of Science ®Google Scholar
• Miller TW, Balko JM, Arteaga CL. Phosphatidylinositol 3-kinase and antiestrogen resistance in breast cancer. J Clin Oncol. 2011;29(33):4452–4461.
   PubMed Web of Science ®Google Scholar
• Mayer IA, Abramson V, Formisano L, et al. A phase Ib study of alpelisib (BYL719), a PI3Kalpha-specific inhibitor, with letrozole in ER+/HER2-negative metastatic breast cancer. Clin Cancer Res. 2016. [Epub ahead of print]
   Web of Science ®Google Scholar
• Sanchez CG, Ma CX, Crowder RJ, et al. Preclinical modeling of combined phosphatidylinositol-3-kinase inhibition with endocrine therapy for estrogen receptor-positive breast cancer. Breast Cancer Res. 2011;13(2):R21.
   PubMed Web of Science ®Google Scholar
• Maira S-M, Pecchi S, Huang A, et al. Identification and characterization of NVP-BKM120, an orally available pan-class I PI3-kinase inhibitor. Mol Cancer Ther. 2012;11(2):317–328.
   PubMed Web of Science ®Google Scholar
• Mayer IA, Abramson VG, Isakoff SJ, et al. Stand up to cancer phase Ib study of pan-phosphoinositide-3-kinase inhibitor buparlisib with letrozole in estrogen receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2014;32(12):1202–1209.
   PubMed Web of Science ®Google Scholar
• Ma CX, Luo J, Naughton M, et al. A phase I trial of BKM120 (Buparlisib) in combination with fulvestrant in postmenopausal women with estrogen receptor-positive metastatic breast cancer. Clin Cancer Res. 2016;22(7):1583–1591.
   PubMed Web of Science ®Google Scholar
• Mayer IA, Fasching PA, Gnant M, et al. Phase II, randomized, placebo-controlled study of BYL719 or buparlisib (BKM120) with letrozole for neoadjuvant treatment of postmenopausal women with HR+/HER2−, PIK3CA mutant or wild-type, breast cancer (BC). J Clin Oncol. 2014;32:5s (suppl; abstr TPS655).
   Google Scholar
• Baselga J, Im S-A, Iwata H, et al. PIK3CA status in circulating tumor DNA (ctDNA) predicts efficacy of buparlisib (BUP) plus fulvestrant (FULV) in postmenopausal women with endocrine-resistant HR+/HER2– advanced breast cancer (BC): first results from the randomized, phase III BELLE-2 trial. Cancer Res. 2015;76(4suppl):abstr S6–01.
   Google Scholar
• Ndubaku CO, Heffron TP, Staben ST, et al. Discovery of 2-{3-[2-(1-isopropyl-3-methyl-1H-1,2-4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl]-1H-pyrazol-1-yl}-2-methylpropanamide (GDC-0032): a beta-sparing phosphoinositide 3-kinase inhibitor with high unbound exposure and robust in vivo antitumor activity. J Med Chem. 2013;56(11):4597–4610.
   PubMed Web of Science ®Google Scholar
• Lopez S, Schwab CL, Cocco E, et al. Taselisib, a selective inhibitor of PIK3CA, is highly effective on PIK3CA-mutated and HER2/neu amplified uterine serous carcinoma in vitro and in vivo. Gynecol Oncol. 2014;135(2):312–317.
   PubMed Web of Science ®Google Scholar
• Hoeflich KP, Guan J, Edgar KA, et al. The PI3K inhibitor taselisib overcomes letrozole resistance in a breast cancer model expressing aromatase. Genes Cancer. 2016;7(3–4):73–85.
   PubMedGoogle Scholar
• Juric D, Krop I, Ramanathan RK, et al. GDC-0032, a beta isoform-sparing PI3K inhibitor: results of a first-in-human phase Ia dose escalation study. Cancer Res. 2013;73(8Suppl):Abstractnr LB–64.
   Google Scholar
• Saura C, Sachdev J, Patel MR, et al. Ph1b study of the PI3K inhibitor taselisib (GDC-0032) in combination with letrozole in patients with hormone receptor-positive advanced breast cancer. Presented at the SABCS; 2014 Dec 9–13; San Antonio, TX (Poster PD5-2).
   Google Scholar
• Saura C, De Azambuja E, Oliveira M, et al. LORELEI: a phase II randomized, double-blind study of neoadjuvant letrozole plus taselisib (GDC-0032) versus letrozole plus placebo in postmenopausal women with ER-positive/HER2-negative, early-stage breast cancer. J Clin Oncol. 2016;34(suppl):abstr TPS613.
   Google Scholar
• Dickler MN, Saura C, Richards DA, et al. A phase II study of the PI3K inhibitor taselisib (GDC-0032) combined with fulvestrant (F) in patients (pts) with HER2-negative (HER2-), hormone receptor-positive (HR+) advanced breast cancer (BC). J Clin Oncol. 2016;34(suppl):abstr 520.
   Google Scholar
• Baselga J, Cortes J, De Laurentiis M, et al. SANDPIPER: phase III study of the PI3-kinase (PI3K) inhibitor taselisib (GDC-0032) plus fulvestrant in patients (pts) with estrogen receptor (ER)-positive, HER2-negative locally advanced or metastatic breast cancer (BC) enriched for pts with PIK3CA-mutant tumors. J Clin Oncol. 2016;34(suppl):abstr TPS617.
   Google Scholar
• Fritsch C, Huang A, Chatenay-Rivauday C, et al. Characterization of the novel and specific PI3Kalpha inhibitor NVP-BYL719 and development of the patient stratification strategy for clinical trials. Mol Cancer Ther. 2014;13(5):1117–1129.
   PubMed Web of Science ®Google Scholar
• Juric D, Argiles G, Burris H, et al. Abstract P6-10-07: phase I study of BYL719, an alpha-specific PI3K inhibitor, in patients with PIK3CA mutant advanced solid tumors: preliminary efficacy and safety in patients with PIK3CA mutant ER-positive (ER+) metastatic breast cancer (MBC). Cancer Res. 2012;72(24Suppl):Abstractnr P6-10-07.
   Google Scholar
• Juric D, Gonzalez-Angulo A, Burris H, et al. Abstract P2-16-14: preliminary safety, pharmacokinetics and anti-tumor activity of BYL719, an alpha-specific PI3K inhibitor in combination with fulvestrant: results from a phase I study. Cancer Res. 2013;73(24Suppl):Abstractnr P2-16-14.
   Google Scholar
• Shah PD, Modi S, Datko FM, et al. Phase I trial of daily PI3Kα inhibitor BYL719 plus letrozole (L) or exemestane (E) for patients (pts) with hormone receptor-positive (HR+) metastatic breast cancer (MBC). J Clin Oncol. 2014;32:5s(suppl;abstr 2605).
   Google Scholar
• André F, Campone M, Ciruelos EM, et al. SOLAR-1: A phase III study of alpelisib + fulvestrant in men and postmenopausal women with HR+/HER2– advanced breast cancer (BC) progressing on or after prior aromatase inhibitor therapy. J Clin Oncol. 2016;34((suppl;abstr TPS618)).
   Web of Science ®Google Scholar
• Pazin MJ, Kadonaga JT. What’s up and down with histone deacetylation and transcription? Cell. 1997;89(3):325–328.
   PubMed Web of Science ®Google Scholar
• Marmorstein R, Roth SY. Histone acetyltransferases: function, structure, and catalysis. Curr Opin Genet Dev. 2001;11(2):155–161.
   PubMed Web of Science ®Google Scholar
• Rajak H, Singh A, Raghuwanshi K, et al. A structural insight into hydroxamic acid based histone deacetylase inhibitors for the presence of anticancer activity. Curr Med Chem. 2014;21(23):2642–2664.
   PubMed Web of Science ®Google Scholar
• Giacinti L, Claudio PP, Lopez M, et al. Epigenetic information and estrogen receptor alpha expression in breast cancer. Oncologist. 2006;11(1):1–8.
   PubMed Web of Science ®Google Scholar
• Ottaviano YL, Issa JP, Parl FF, et al. Methylation of the estrogen receptor gene CpG island marks loss of estrogen receptor expression in human breast cancer cells. Cancer Res. 1994;54(10):2552–2555.
   PubMed Web of Science ®Google Scholar
• Kawai H, Li H, Avraham S, et al. Overexpression of histone deacetylase HDAC1 modulates breast cancer progression by negative regulation of estrogen receptor alpha. Int J Cancer. 2003;107(3):353–358.
   PubMed Web of Science ®Google Scholar
• Sabnis GJ, Goloubeva O, Chumsri S, et al. Functional activation of the estrogen receptor-alpha and aromatase by the HDAC inhibitor entinostat sensitizes ER-negative tumors to letrozole. Cancer Res. 2011;71(5):1893–1903.
   PubMed Web of Science ®Google Scholar
• Sabnis GJ, Goloubeva OG, Kazi AA, et al. HDAC inhibitor entinostat restores responsiveness of letrozole-resistant MCF-7Ca xenografts to aromatase inhibitors through modulation of Her-2. Mol Cancer Ther. 2013;12(12):2804–2816.
   PubMed Web of Science ®Google Scholar
• Yardley DA, Ismail-Khan RR, Melichar B, et al. Randomized phase II, double-blind, placebo-controlled study of exemestane with or without entinostat in postmenopausal women with locally recurrent or metastatic estrogen receptor-positive breast cancer progressing on treatment with a nonsteroidal aromatase inhibitor. J Clin Oncol. 2013;31(17):2128–2135.
   PubMed Web of Science ®Google Scholar
• DeMichele A, Clark AS, Tan KS, et al. CDK 4/6 inhibitor palbociclib (PD0332991) in Rb+ advanced breast cancer: phase II activity, safety, and predictive biomarker assessment. Clin Cancer Res. 2015;21(5):995–1001.
   PubMed Web of Science ®Google Scholar
• Hortobagyi GN, Chen D, Piccart M, et al. Correlative analysis of genetic alterations and everolimus benefit in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: results from BOLERO-2. J Clin Oncol. 2016;34(5):419–426.
   PubMed Web of Science ®Google Scholar