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Review

Molecularly targeted therapy and immunotherapy for hormone receptor‑positive/human epidermal growth factor receptor 2‑negative advanced breast cancer (Review)

  • Authors:
    • Yuhua Song
    • Lin He
    • Yaling Wang
    • Qian Wu
    • Wenzhi Huang
  • View Affiliations / Copyright

    Affiliations: Breast Disease Center, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, P.R. China, Department of Oncology, The Second Affiliated Hospital of Medical College of Qingdao University, Qingdao, Shandong 266000, P.R. China, Department of Oncology, The PLA Navy Anqing Hospital, Anqing, Anhui 246000, P.R. China
  • Pages: 3-13
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    Published online on: April 21, 2020
       https://doi.org/10.3892/or.2020.7589
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Abstract

The advent of targeted therapy for hormone receptor‑positive/human epidermal growth factor receptor 2‑negative advanced breast cancer (HR+/HER2‑ aBC) provides a novel therapeutic approach other than endocrine therapy. One targeted signaling pathway and three immune‑checkpoints have been demonstrated to be in association with tumor proliferation and growth in HR+/HER2‑ aBC. A number of phosphoinositide 3‑kinase/AKT/mammalian target of rapamycin signaling pathway inhibitors demonstrate clinical activity against this tumor subtype. The CDK4/6 inhibitors as a single agent or in combination with endocrine therapy have produced promising tumor response with acceptable toxicity in patients with HR+/HER2‑ aBC. Programmed death 1/programmed death ligand 1 (PD1/PD‑L1) and cytotoxic T lymphocyte antigen‑4 inhibitors can also produce an antitumor immune response, which provides a proof‑of‑principle for the initial utilization of immunotherapy in breast cancer. The aim of the present review was to discuss the mechanisms of action, clinical efficacy and safety profiles of all the targeted biological therapies and immunotherapies that have been approved or are currently under evaluation for HR+/HER2‑ aBC.
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1 

Parkin DM, Pisani P and Ferlay J: Global cancer statistics. CA Cancer J Clin. 49:33–64, 1. 1999. View Article : Google Scholar : PubMed/NCBI

2 

Gradishar WJ, Anderson BO, Balassanian R, Blair SL, Burstein HJ, Cyr A, Elias AD, Farrar WB, Forero A, Giordano SH, et al: Invasive breast cancer version 1.2016, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 14:324–354. 2016. View Article : Google Scholar : PubMed/NCBI

3 

Kwa M, Li X, Novik Y, Oratz R, Jhaveri K, Wu J, Gu P, Meyers M, Muggia F, Speyer J, et al: Serial immunological parameters in a phase II trial of exemestane and low-dose oral cyclophosphamide in advanced hormone receptor-positive breast canc. Breast Cancer Res Treat. 168:57–67. 2018. View Article : Google Scholar : PubMed/NCBI

4 

Baselga J, Campone M, Piccart M, Burris HA III, Rugo HS, Sahmoud T, Noguchi S, Gnant M, Pritchard KI, Lebrun F, et al: Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med. 366:520–529. 2012. View Article : Google Scholar : PubMed/NCBI

5 

Jiang Z, Li W, Hu X, Zhang Q, Sun T, Cui S, Wang S, Ouyang Q, Yin Y, Geng C, et al: Tucidinostat plus exemestane for postmenopausal patients with advanced, hormone receptor-positive breast cancer (ACE): A randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 20:806–815. 2019. View Article : Google Scholar : PubMed/NCBI

6 

Esteva FJ, Hubbard-Lucey VM, Tang J and Pusztai L: Immunotherapy and targeted therapy combinations in metastatic breast cancer. Lancet Oncol. 20:e175–e186. 2019. View Article : Google Scholar : PubMed/NCBI

7 

Bianchini G, Qi Y, Alvarez RH, Iwamoto T, Coutant C, Ibrahim NK, Valero V, Cristofanilli M, Green MC, Radvanyi L, et al: Molecular anatomy of breast cancer stroma and its prognostic value in estrogen receptor-positive and -negative cancers. J Clin Oncol. 28:4316–4323. 2010. View Article : Google Scholar : PubMed/NCBI

8 

Rugo HS, Delord JP, Im SA, Ott PA, Piha-Paul SA, Bedard PL, Sachdev J, Le Tourneau C, van Brummelen EMJ, Varga A, et al: Safety and antitumor activity of pembrolizumab in patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer. Clin Cancer Res. 24:2804–2811. 2018. View Article : Google Scholar : PubMed/NCBI

9 

Dirix LY, Takacs I, Jerusalem G, Nikolinakos P, Arkenau HT, Forero-Torres A, Boccia R, Lippman ME, Somer R, Smakal M, et al: Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: A phase 1b JAVELIN Solid Tumor study. Breast Cancer Res Treat. 167:671–686. 2018. View Article : Google Scholar : PubMed/NCBI

10 

Santa-Maria CA, Kato T, Park JH, Kiyotani K, Rademaker A, Shah AN, Gross L, Blanco LZ, Jain S, Flaum L, et al: A pilot study of durvalumab and tremelimumab and immunogenomic dynamics in metastatic breast cancer. Oncotarget. 9:18985–18996. 2018. View Article : Google Scholar : PubMed/NCBI

11 

Vonderheide RH, LoRusso PM, Khalil M, Gartner EM, Khaira D, Soulieres D, Dorazio P, Trosko JA, Rüter J, Mariani GL, et al: Tremelimumab in combination with exemestane in patients with advanced breast cancer and treatment-associated modulation of inducible costimulator expression on patient T cells. Clin Cancer Res. 16:3485–3494. 2010. View Article : Google Scholar : PubMed/NCBI

12 

Lindsley CW: The Akt/PKB family of protein kinases: A review of small molecule inhibitors and progress towards target validation: A 2009 update. Curr Top Med Chem. 10:458–477. 2010. View Article : Google Scholar : PubMed/NCBI

13 

Stemke-Hale K, Gonzalez-Angulo AM, Lluch A, Neve RM, Kuo WL, Davies M, Carey M, Hu Z, Guan Y, Sahin A, et al: An integrative genomic and proteomic analysis of PIK3CA, PTEN, and AKT mutations in breast cancer. Cancer Res. 68:6084–6091. 2008. View Article : Google Scholar : PubMed/NCBI

14 

Huang GS, Brouwer-Visser J, Ramirez MJ, Kim CH, Hebert TM, Lin J, Arias-Pulido H, Qualls CR, Prossnitz ER, Goldberg GL, et al: Insulin-like growth factor 2 expression modulates Taxol resistance and is a candidate biomarker for reduced disease-free survival in ovarian cancer. Clin Cancer Res. 16:2999–3010. 2010. View Article : Google Scholar : PubMed/NCBI

15 

Pérez-Tenorio G and Stål O; Southeast Sweden Breast Cancer Group, : Activation of AKT/PKB in breast cancer predicts a worse outcome among endocrine treated patients. Br J Cancer. 86:540–545. 2002. View Article : Google Scholar : PubMed/NCBI

16 

Chen X, Zhao M, Hao M, Sun X, Wang J, Mao Y, Zu L, Liu J, Shen Y, Wang J and Shen K: Dual inhibition of PI3K and mTOR mitigates compensatory AKT activation and improves tamoxifen response in breast cancer. Mol Cancer Res. 11:1269–1278. 2013. View Article : Google Scholar : PubMed/NCBI

17 

Mabuchi S, Ohmichi M, Kimura A, Hisamoto K, Hayakawa J, Nishio Y, Adachi K, Takahashi K, Arimoto-Ishida E, Nakatsuji Y, et al: Inhibition of phosphorylation of BAD and Raf-1 by Akt sensitizes human ovarian cancer cells to paclitaxel. J Biol Chem. 277:33490–33500. 2002. View Article : Google Scholar : PubMed/NCBI

18 

Boulay A, Rudloff J, Ye J, Zumstein-Mecker S, O'Reilly T, Evans DB, Chen S and Lane HA: Dual inhibition of mTOR and estrogen receptor signaling in vitro induces cell death in models of breast cancer. Clin Cancer Res. 11:5319–5328. 2005. View Article : Google Scholar : PubMed/NCBI

19 

Lui A, New J, Ogony J, Thomas S and Lewis-Wambi J: Everolimus downregulates estrogen receptor and induces autophagy in aromatase inhibitor-resistant breast cancer cells. BMC Cancer. 16:4872016. View Article : Google Scholar : PubMed/NCBI

20 

Mayer IA, Abramson VG, Isakoff SJ, Forero A, Balko JM, Kuba MG, Sanders ME, Yap JT, Van den Abbeele AD, Li Y, 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. 32:1202–1209. 2014. View Article : Google Scholar : PubMed/NCBI

21 

Ma CX, Luo J, Naughton M, Ademuyiwa F, Suresh R, Griffith M, Griffith OL, Skidmore ZL, Spies NC, Ramu A, 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. 22:1583–1591. 2016. View Article : Google Scholar : PubMed/NCBI

22 

Baselga J, Im SA, Iwata H, Cortés J, De Laurentiis M, Jiang Z, Arteaga CL, Jonat W, Clemons M, Ito Y, et al: Buparlisib plus fulvestrant versus placebo plus fulvestrant in postmenopausal, hormone receptor-positive, HER2-negative, advanced breast cancer (BELLE-2): A randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 18:904–916. 2017. View Article : Google Scholar : PubMed/NCBI

23 

Di Leo A, Johnston S, Lee KS, Ciruelos E, Lønning PE, Janni W, O'Regan R, Mouret-Reynier MA, Kalev D, Egle D, et al: Buparlisib plus fulvestrant in postmenopausal women with hormone-receptor-positive, HER2-negative, advanced breast cancer progressing on or after mTOR inhibition (BELLE-3): A randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 19:87–100. 2018. View Article : Google Scholar : PubMed/NCBI

24 

Mayer IA, Abramson VG, Formisano L, Balko JM, Estrada MV, Sanders ME, Juric D, Solit D, Berger MF, Won HH, et al: A phase Ib study of alpelisib (BYL719), a PI3Kα-specific inhibitor, with letrozole in ER+/HER2-metastatic breast cancer. Clin Cancer Res. 23:26–34. 2017. View Article : Google Scholar : PubMed/NCBI

25 

Juric D, Janku F, Rodón J, Burris HA, Mayer IA, Schuler M, Seggewiss-Bernhardt R, Gil-Martin M, Middleton MR, Baselga J, et al: Alpelisib plus fulvestrant in PIK3CA-Altered and PIK3CA-wild-type estrogen receptor-positive advanced breast cancer: A phase 1b clinical trial. JAMA Oncol. 5:e1844752019. View Article : Google Scholar : PubMed/NCBI

26 

Mayer IA, Prat A, Egle D, Blau S, Fidalgo JAP, Gnant M, Fasching PA, Colleoni M, Wolff AC, Winer EP, et al: A phase II randomized study of neoadjuvant letrozole plus alpelisib for hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer (NEO-ORB). Clin Cancer Res. 25:2975–2987. 2019. View Article : Google Scholar : PubMed/NCBI

27 

André F, Ciruelos E, Rubovszky G, Campone M, Loibl S, Rugo HS, Iwata H, Conte P, Mayer IA, Kaufman B, et al: Alpelisib for PIK3CA-mutated, hormone receptor-positive advanced breast cancer. N Engl J Med. 380:1929–1940. 2019. View Article : Google Scholar : PubMed/NCBI

28 

Li Y: MK-2206: A potent oral allosteric AKT inhibitor. Cancer Res. 69:DDT01–1. 2009.

29 

Ma CX, Sanchez C, Gao F, Crowder R, Naughton M, Pluard T, Creekmore A, Guo Z, Hoog J, Lockhart AC, et al: A phase I study of the AKT inhibitor MK-2206 in combination with hormonal therapy in postmenopausal women with estrogen receptor-positive metastatic breast cancer. Clin Cancer Res. 22:2650–2658. 2016. View Article : Google Scholar : PubMed/NCBI

30 

Xing Y, Lin NU, Maurer MA, Chen H, Mahvash A, Sahin A, Akcakanat A, Li Y, Abramson V, Litton J, et al: Phase II trial of AKT inhibitor MK-2206 in patients with advanced breast cancer who have tumors with PIK3CA or AKT mutations, and/or PTEN loss/PTEN mutation. Breast Cancer Res. 21:782019. View Article : Google Scholar : PubMed/NCBI

31 

Ma CX, Suman V, Goetz MP, Northfelt D, Burkard ME, Ademuyiwa F, Naughton M, Margenthaler J, Aft R, Gray R, et al: A phase II trial of neoadjuvant MK-2206, an AKT inhibitor, with anastrozole in clinical stage II or III PIK3CA-mutant ER-positive and HER2-negative breast cancer. Clin Cancer Res. 23:6823–6832. 2017. View Article : Google Scholar : PubMed/NCBI

32 

Banerji U, Dean EJ, Pérez-Fidalgo JA, Batist G, Bedard PL, You B, Westin SN, Kabos P, Garrett MD, Tall M, et al: A Phase I open-label study to identify a dosing regimen of the Pan-AKT inhibitor AZD5363 for evaluation in solid tumors and in PIK3CA-mutated breast and gynecologic cancers. Clin Cancer Res. 24:2050–2059. 2018. View Article : Google Scholar : PubMed/NCBI

33 

Turner NC, Alarcón E, Armstrong AC, Philco M, López Chuken YA, Sablin MP, Tamura K, Gómez Villanueva A, Pérez-Fidalgo JA, Cheung SYA, et al: BEECH: A dose-finding run-in followed by a randomised phase II study assessing the efficacy of AKT inhibitor capivasertib (AZD5363) combined with paclitaxel in patients with estrogen receptor-positive advanced or metastatic breast cancer, and in a PIK3CA mutant sub-population. Ann Oncol. 30:774–780. 2019. View Article : Google Scholar : PubMed/NCBI

34 

Ribas R, Pancholi S, Guest SK, Marangoni E, Gao Q, Thuleau A, Simigdala N, Polanska UM, Campbell H, Rani A, et al: AKT antagonist AZD5363 influences estrogen receptor function in endocrine-resistant breast cancer and synergizes with fulvestrant (ICI182780) in vivo. Mol Cancer Ther. 14:2035–2048. 2015. View Article : Google Scholar : PubMed/NCBI

35 

Efeyan A and Sabatini DM: mTOR and cancer: Many loops in one pathway. Curr Opin Cell Biol. 22:169–176. 2010. View Article : Google Scholar : PubMed/NCBI

36 

Baselga J, Semiglazov V, van Dam P, Manikhas A, Bellet M, Mayordomo J, Campone M, Kubista E, Greil R, Bianchi G, et al: Phase II randomized study of neoadjuvant everolimus plus letrozole compared with placebo plus letrozole in patients with estrogen receptor-positive breast cancer. J Clin Oncol. 27:2630–2637. 2009. View Article : Google Scholar : PubMed/NCBI

37 

Tesch H, Stoetzer O, Decker T, Kurbacher CM, Marmé F, Schneeweiss A, Mundhenke C, Distelrath A, Fasching PA, Lux MP, et al: Efficacy and safety of everolimus plus exemestane in postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer: Results of the single-arm, phase IIIB 4EVER trial. Int J Cancer. 144:877–885. 2019. View Article : Google Scholar : PubMed/NCBI

38 

Bachelot T, Bourgier C, Cropet C, Ray-Coquard I, Ferrero JM, Freyer G, Abadie-Lacourtoisie S, Eymard JC, Debled M, Spaëth D, 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. 30:2718–2724. 2012. View Article : Google Scholar : PubMed/NCBI

39 

Royce M, Bachelot T, Villanueva C, Özgüroglu M, Azevedo SJ, Cruz FM, Debled M, Hegg R, Toyama T, Falkson C, et al: Everolimus plus endocrine therapy for postmenopausal women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: A clinical trial. JAMA Oncol. 4:977–984. 2018. View Article : Google Scholar : PubMed/NCBI

40 

Jerusalem G, de Boer RH, Hurvitz S, Yardley DA, Kovalenko E, Ejlertsen B, Blau S, Özgüroglu M, Landherr L, Ewertz M, et al: Everolimus plus exemestane vs everolimus or capecitabine monotherapy for estrogen receptor-positive, HER2-negative advanced breast cancer: The BOLERO-6 randomized clinical trial. JAMA Oncol. 4:1367–1374. 2018. View Article : Google Scholar : PubMed/NCBI

41 

Generali D, Venturini S, Rognoni C, Ciani O, Pusztai L, Loi S, Jerusalem G, Bottini A and Tarricone R: A network meta-analysis of everolimus plus exemestane versus chemotherapy in the first- and second-line treatment of estrogen receptor-positive metastatic breast cancer. Breast Cancer Res Treat. 152:95–117. 2015. View Article : Google Scholar : PubMed/NCBI

42 

Weinberg RA: The retinoblastoma protein and cell cycle control. Cell. 81:323–330. 1995. View Article : Google Scholar : PubMed/NCBI

43 

Sherr CJ and Roberts JM: CDK inhibitors: Positive and negative regulators of G1-phase progression. Genes Dev. 13:1501–1512. 1999. View Article : Google Scholar : PubMed/NCBI

44 

Carnero A and Hannon GJ: The INK4 family of CDK inhibitors. Curr Top Microbiol Immunol. 227:43–55. 1998.PubMed/NCBI

45 

Hall M and Peters G: Genetic alterations of cyclins, cyclin-dependent kinases, and Cdk inhibitors in human cancer. Adv Cancer Res. 68:67–108. 1996. View Article : Google Scholar : PubMed/NCBI

46 

Sherr CJ: Cancer cell cycles. Science. 274:1672–1677. 1996. View Article : Google Scholar : PubMed/NCBI

47 

Shapiro GI: Cyclin-dependent kinase pathways as targets for cancer treatment. J Clin Oncol. 24:1770–1783. 2006. View Article : Google Scholar : PubMed/NCBI

48 

Bates GJ, Fox SB, Han C, Leek RD, Garcia JF, Harris AL and Banham AH: Quantification of regulatory T cells enables the identification of high-risk breast cancer patients and those at risk of late relapse. J Clin Oncol. 24:5373–5380. 2006. View Article : Google Scholar : PubMed/NCBI

49 

Fry DW, Harvey PJ, Keller PR, Elliott WL, Meade M, Trachet E, Albassam M, Zheng X, Leopold WR, Pryer NK and Toogood PL: Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts. Mol Cancer Ther. 3:1427–1438. 2004.PubMed/NCBI

50 

Finn RS, Dering J, Conklin D, Kalous O, Cohen DJ, Desai AJ, Ginther C, Atefi M, Chen I, Fowst C, 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. 11:R772009. View Article : Google Scholar : PubMed/NCBI

51 

Finn RS, Crown JP, Lang I, Boer K, Bondarenko IM, Kulyk SO, Ettl J, Patel R, Pinter T, Schmidt M, 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. 16:25–35. 2015. View Article : Google Scholar : PubMed/NCBI

52 

Finn RS, Martin M, Rugo HS, Jones S, Im SA, Gelmon K, Harbeck N, Lipatov ON, Walshe JM, Moulder S, et al: Palbociclib and letrozole in advanced breast cancer. N Engl J Med. 375:1925–1936. 2016. View Article : Google Scholar : PubMed/NCBI

53 

Cristofanilli M, Turner NC, Bondarenko I, Ro J, Im SA, Masuda N, Colleoni M, DeMichele A, Loi S, Verma S, 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. 17:425–439. 2016. View Article : Google Scholar : PubMed/NCBI

54 

Kim S, Loo A, Chopra R, Caponigro G, Huang A, Vora S, Parasuraman S, Howard S, Keen N, Sellers W and Brain C. LEE011: An orally bioavailable, selective small molecule inhibitor of CDK4/6-Reactivating Rb in cancer. Mol Cancer Ther. 12 (11 Suppl):PR022013.

55 

O'Brien NA, Tomaso ED, Ayala R, Tong L, Issakhanian S, Linnartz R, Finn RS, Hirawat S and Slamon DJ: In vivo efficacy of combined targeting of CDK4/6, ER and PI3K signaling in ER+breast cancer. Cancer Res. 74 (19 Suppl):S47562014.

56 

Juric D, Munster PN, Campone M, Ismail-Khan R, García-Estevez L, Hamilton EP, Becerra C, De Boer RH, Hui R and Goncalves A: 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. 34 (15 Suppl):S5682016. View Article : Google Scholar

57 

Tripathy D Sohn J, Im SA, Colleoni M, Franke F, Bardia A, Harbeck N, Hurvitz S, Chow L, Lee KS, et al: First-line ribociclib vs. placebo with goserelin and tamoxifen or a non-steroidal aromatase inhibitor in premenopausal women with hormone receptor-positive, HER2- negative advanced breast cancer: Results from the randomized phase III MONALEESA-7 trial. Cancer Res. 78 (4 Suppl):GS2–05. 2018.

58 

Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Paluch-Shimon S, Campone M, Blackwell KL, André F, Winer EP, et al: Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N Engl J Med. 375:1738–1748. 2016. View Article : Google Scholar : PubMed/NCBI

59 

Slamon DJ, Neven P, Chia S, Fasching PA, De Laurentiis M, Im SA, Petrakova K, Bianchi GV, Esteva FJ, Martín M, et al: Phase III randomized study of ribociclib and fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: MONALEESA-3. J Clin Oncol. 36:2465–2472. 2018. View Article : Google Scholar : PubMed/NCBI

60 

Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Paluch-Shimon S, Campone M, Petrakova K, Blackwell KL, Winer EP, et al: Updated results from MONALEESA-2, a phase III trial of first-line ribociclib plus letrozole versus placebo plus letrozole in hormone receptor-positive, HER2-negative advanced breast cancer. Ann Oncol. 29:1541–1547. 2018. View Article : Google Scholar : PubMed/NCBI

61 

Gelbert LM, Cai S, Lin X, Sanchez-Martinez C, Del Prado M, Lallena MJ, Torres R, Ajamie RT, Wishart GN, Flack RS, 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. 32:825–837. 2014. View Article : Google Scholar : PubMed/NCBI

62 

Patnaik A, Rosen LS, Tolaney SM, Tolcher AW, Goldman JW, Gandhi L, Papadopoulos KP, Beeram M, Rasco DW, Hilton JF, 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. 6:740–753. 2016. View Article : Google Scholar : PubMed/NCBI

63 

Dickler MN, Tolaney SM, Rugo HS, Cortés J, Diéras V, Patt D, Wildiers H, Hudis CA, O'Shaughnessy J, Zamora E, et al: MONARCH 1, a phase II study of abemaciclib, a CDK4 and CDK6 inhibitor, as a single agent, in patients with refractory HR+/HER2−metastatic breast cancer. Clin Cancer Res. 23:5218–5224. 2017. View Article : Google Scholar : PubMed/NCBI

64 

Sledge GW Jr, Toi M, Neven P, Sohn J, Inoue K, Pivot X, Burdaeva O, Okera M, Masuda N, Kaufman PA, et al: MONARCH 2: Abemaciclib in combination with fulvestrant in women with HR+/HER2-advanced breast cancer who had progressed while receiving endocrine therapy. J Clin Oncol. 35:2875–2884. 2017. View Article : Google Scholar : PubMed/NCBI

65 

Iwai Y, Okazaki T, Nishimura H, Kawasaki A, Yagita H and Honjo T: Microanatomical localization of PD-1 in human tonsils. Immunol Lett. 83:215–220. 2002. View Article : Google Scholar : PubMed/NCBI

66 

Okazaki T, Maeda A, Nishimura H, Kurosaki T and Honjo T: PD-1 immunoreceptor inhibits B cell receptor-mediated signaling by recruiting src homology 2-domain-containing tyrosine phosphatase 2 to phosphotyrosine. Proc Natl Acad Sci USA. 98:13866–13871. 2001. View Article : Google Scholar : PubMed/NCBI

67 

Yokosuka T, Takamatsu M, Kobayashi-Imanishi W, Hashimoto-Tane A, Azuma M and Saito T: Programmed cell death 1 forms negative costimulatory microclusters that directly inhibit T cell receptor signaling by recruiting phosphatase SHP2. J Exp Med. 209:1201–1217. 2012. View Article : Google Scholar : PubMed/NCBI

68 

Sheppard KA, Fitz LJ, Lee JM, Benander C, George JA, Wooters J, Qiu Y, Jussif JM, Carter LL, Wood CR and Chaudhary D: PD-1 inhibits T-cell receptor induced phosphorylation of the ZAP70/CD3zeta signalosome and downstream signaling to PKCtheta. Febs Lett. 574:37–41. 2004. View Article : Google Scholar : PubMed/NCBI

69 

Iwai Y, Ishida M, Tanaka Y, Okazaki T, Honjo T and Minato N: Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc Natl Acad Sci USA. 99:12293–12297. 2002. View Article : Google Scholar : PubMed/NCBI

70 

Ali HR, Glont SE, Blows FM, Provenzano E, Dawson SJ, Liu B, Hiller L, Dunn J, Poole CJ, Bowden S, et al: PD-L1 protein expression in breast cancer is rare, enriched in basal-like tumours and associated with infiltrating lymphocytes. Ann Oncol y. 26:1488–1493. 2015. View Article : Google Scholar

71 

Nanda R, Chow LQ, Dees EC, Berger R, Gupta S, Geva R, Pusztai L, Pathiraja K, Aktan G, Cheng JD, et al: Pembrolizumab in patients with advanced triple-negative breast cancer: Phase Ib KEYNOTE-012 study. J Clin Oncol. 34:2460–2467. 2016. View Article : Google Scholar : PubMed/NCBI

72 

Adams S, Schmid P, Rugo HS, Winer EP, Loirat D, Awada A, Cescon DW, Iwata H, Campone M, Nanda R, et al: Pembrolizumab monotherapy for previously treated metastatic triple-negative breast cancer: Cohort A of the phase II KEYNOTE-086 study. Ann Oncol. 30:397–404. 2019. View Article : Google Scholar : PubMed/NCBI

73 

Adams S, Loi S, Toppmeyer D, Cescon DW, De Laurentiis M, Nanda R, Winer EP, Mukai H, Tamura K, Armstrong A, et al: Pembrolizumab monotherapy for previously untreated, PD-L1-positive, metastatic triple-negative breast cancer: Cohort B of the phase II KEYNOTE-086 study. Ann Oncol. 30:405–411. 2019. View Article : Google Scholar : PubMed/NCBI

74 

Greenwald RJ, Freeman GJ and Sharpe AH: The B7 family revisited. Annu Rev Immunol. 23:515–548. 2005. View Article : Google Scholar : PubMed/NCBI

75 

Peggs KS, Quezada SA, Korman AJ and Allison JP: Principles and use of anti-CTLA4 antibody in human cancer immunotherapy. Curr Opin Immunol. 18:206–213. 2006. View Article : Google Scholar : PubMed/NCBI

76 

Egen JG, Kuhns MS and Allison JP: CTLA-4: New insights into its biological function and use in tumor immunotherapy. Nat Immunol. 3:611–618. 2002. View Article : Google Scholar : PubMed/NCBI

77 

Demaria S, Kawashima N, Yang AM, Devitt ML, Babb JS, Allison JP and Formenti SC: Immune-mediated inhibition of metastases after treatment with local radiation and CTLA-4 blockade in a mouse model of breast cancer. Clin Cancer Res. 11:728–734. 2005.PubMed/NCBI

78 

Mokyr MB, Kalinichenko T, Gorelik L and Bluestone JA: Realization of the therapeutic potential of CTLA-4 blockade in low-dose chemotherapy-treated tumor-bearing mice. Cancer Res. 58:5301–5304. 1998.PubMed/NCBI

79 

Attia P, Phan GQ, Maker AV, Robinson MR, Quezado MM, Yang JC, Sherry RM, Topalian SL, Kammula US, Royal RE, et al: Autoimmunity correlates with tumor regression in patients with metastatic melanoma treated with anti-cytotoxic T-lymphocyte antigen-4. J Clin Oncol. 23:6043–6053. 2005. View Article : Google Scholar : PubMed/NCBI

80 

Tarhini AA and Kirkwood JM: Tremelimumab (CP-675,206): a fully human anticytotoxic T lymphocyte-associated antigen 4 monoclonal antibody for treatment of patients with advanced cancers. Expert Opin Biol Ther. 8:1583–1593. 2008. View Article : Google Scholar : PubMed/NCBI

81 

Ribas A: Overcoming immunologic tolerance to melanoma: Targeting CTLA-4 with tremelimumab (CP-675,206). Oncologist. 13 (Suppl 4):S10–S15. 2008. View Article : Google Scholar

82 

Ribas A, Camacho LH, Lopez-Berestein G, Pavlov D, Bulanhagui CA, Millham R, Comin-Anduix B, Reuben JM, Seja E, Parker CA, et al: Antitumor activity in melanoma and anti-self responses in a phase I trial with the anti-cytotoxic T lymphocyte-associated antigen 4 monoclonal antibody CP-675,206. J Clin Oncol. 23:8968–8977. 2005. View Article : Google Scholar : PubMed/NCBI

83 

Ribas A, Comin-Anduix B, Economou JS, Donahue TR, de la Rocha P, Morris LF, Jalil J, Dissette VB, Shintaku IP, Glaspy JA, et al: Intratumoral immune cell infiltrates, FoxP3, and indoleamine 2,3-dioxygenase in patients with melanoma undergoing CTLA4 blockade. Clin Cancer Res. 15:390–399. 2009. View Article : Google Scholar : PubMed/NCBI

84 

Camacho LH, Antonia S, Sosman J, Kirkwood JM, Gajewski TF, Redman B, Pavlov D, Bulanhagui C, Bozon VA, Gomez-Navarro J and bRibas A: Phase I/II trial of tremelimumab in patients with metastatic melanoma. J Clin Oncol. 27:1075–1081. 2009. View Article : Google Scholar : PubMed/NCBI

85 

Ribas A, Hauschild A, Kefford R, Punt CJ, Haanen JB, Marmol M, Garbe C, Gomez-Navarro J, Pavlov D and Marshall M: Phase III, open-label, randomized, comparative study of tremelimumab (CP-675,206) and chemotherapy [temozolomide (TMZ) or dacarbazine (DTIC)] in patients with advanced melanoma. J Clin Oncol. 26 (15 Suppl):LBA90112008. View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Song Y, He L, Wang Y, Wu Q and Huang W: Molecularly targeted therapy and immunotherapy for hormone receptor‑positive/human epidermal growth factor receptor 2‑negative advanced breast cancer (Review). Oncol Rep 44: 3-13, 2020.
APA
Song, Y., He, L., Wang, Y., Wu, Q., & Huang, W. (2020). Molecularly targeted therapy and immunotherapy for hormone receptor‑positive/human epidermal growth factor receptor 2‑negative advanced breast cancer (Review). Oncology Reports, 44, 3-13. https://doi.org/10.3892/or.2020.7589
MLA
Song, Y., He, L., Wang, Y., Wu, Q., Huang, W."Molecularly targeted therapy and immunotherapy for hormone receptor‑positive/human epidermal growth factor receptor 2‑negative advanced breast cancer (Review)". Oncology Reports 44.1 (2020): 3-13.
Chicago
Song, Y., He, L., Wang, Y., Wu, Q., Huang, W."Molecularly targeted therapy and immunotherapy for hormone receptor‑positive/human epidermal growth factor receptor 2‑negative advanced breast cancer (Review)". Oncology Reports 44, no. 1 (2020): 3-13. https://doi.org/10.3892/or.2020.7589
Copy and paste a formatted citation
x
Spandidos Publications style
Song Y, He L, Wang Y, Wu Q and Huang W: Molecularly targeted therapy and immunotherapy for hormone receptor‑positive/human epidermal growth factor receptor 2‑negative advanced breast cancer (Review). Oncol Rep 44: 3-13, 2020.
APA
Song, Y., He, L., Wang, Y., Wu, Q., & Huang, W. (2020). Molecularly targeted therapy and immunotherapy for hormone receptor‑positive/human epidermal growth factor receptor 2‑negative advanced breast cancer (Review). Oncology Reports, 44, 3-13. https://doi.org/10.3892/or.2020.7589
MLA
Song, Y., He, L., Wang, Y., Wu, Q., Huang, W."Molecularly targeted therapy and immunotherapy for hormone receptor‑positive/human epidermal growth factor receptor 2‑negative advanced breast cancer (Review)". Oncology Reports 44.1 (2020): 3-13.
Chicago
Song, Y., He, L., Wang, Y., Wu, Q., Huang, W."Molecularly targeted therapy and immunotherapy for hormone receptor‑positive/human epidermal growth factor receptor 2‑negative advanced breast cancer (Review)". Oncology Reports 44, no. 1 (2020): 3-13. https://doi.org/10.3892/or.2020.7589
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