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Cancer journal (Sudbury, Mass.)
2021 Jan-Feb 01;27 (1): 50-58.

Targeted Treatment of Triple-Negative Breast Cancer.

Joanna A Young, Antoinette R Tan
Author Information
  1. Joanna A Young: From the Levine Cancer Institute, Atrium Health, Charlotte, NC.
PMID: 33475293 DOI: 10.1097/PPO.0000000000000495

Abstract

ABSTRACT: Triple-negative breast cancer is increasingly recognized as a heterogeneous entity that can be categorized according to histologic, molecular, and clinical subtypes. While chemotherapy remains the backbone of treatment for this disease, there are now several available targeted agents including immunotherapy, poly(adenosine diphosphate-ribose) polymerase inhibitors, and most recently a Food and Drug Administration-approved antibody-drug conjugate sacituzumab govitecan-hziy as a third-line treatment of metastatic triple-negative breast cancer. We review several actionable targets for triple-negative breast cancer and describe promising nonimmunotherapeutic agents including cyclin-dependent kinase inhibitors, androgen receptor inhibitors, mitogen-activated protein kinase inhibitors, phosphoinositide 3-kinase inhibitors, AKT (also known as protein kinase B) inhibitors, and antibody-drug conjugates.

References

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69:7–34.
  2. Bertucci F, Ng CKY, Patsouris A, et al. Genomic characterization of metastatic breast cancers. Nature. 2019;569:560–564.
  3. Lehmann BD, Bauer JA, Chen X, et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest. 2011;121:2750–2767.
  4. Chan JJ, Tan TJY, Dent RA. Are there any clinically relevant subgroups of triple-negative breast cancer in 2018? J Oncol Pract. 2018;14:281–289.
  5. Relf M, Lejeune S, Scott PAE, et al. Expression of the angiogenic factors vascular endothelial cell growth factor, acidic and basic fibroblast growth factor, tumor growth factor β-1, platelet-derived endothelial cell growth factor, placenta growth factor, and pleiotrophin in human primary br. Cancer Res. 1997;57:963–969.
  6. Linderholm BK, Hellborg H, Johansson U, et al. Significantly higher levels of vascular endothelial growth factor (VEGF) and shorter survival times for patients with primary operable triple-negative breast cancer. Ann Oncol. 2009;20:1639–1646.
  7. Miller KD, Chap LI, Holmes FA, et al. Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. J Clin Oncol. 2005;23:792–799.
  8. Miller K, Wang M, Gralow J, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med. 2007;357:2666–2676.
  9. Robert NJ, Diéras V, Glaspy J, et al. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2–negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011;29:1252–1260.
  10. Bear HD, Tang G, Rastogi P, et al. Bevacizumab added to neoadjuvant chemotherapy for breast cancer. N Engl J Med. 2012;366:310–320.
  11. Gerber B, Loibl S, Eidtmann H, et al. Neoadjuvant bevacizumab and anthracycline-taxane-based chemotherapy in 678 triple-negative primary breast cancers; results from the geparquinto study (GBG 44). Ann Oncol. 2013;24:2978–2984.
  12. Rugo HS, Stopeck AT, Joy AA, et al. Randomized, placebo-controlled, double-blind, phase II study of axitinib plus docetaxel versus docetaxel plus placebo in patients with metastatic breast cancer. J Clin Oncol. 2011;29:2459–2465.
  13. Robert NJ, Saleh MN, Paul D, et al. Sunitinib plus paclitaxel versus bevacizumab plus paclitaxel for first-line treatment of patients with advanced breast cancer: a phase III, randomized, open-label trial. Clin Breast Cancer. 2011;11:82–92.
  14. Hafez N, Soliman HH, Fu S, et al. Preliminary efficacy data of triple-negative breast cancer cohort of NCI 9881 study: a phase II study of cediranib in combination with olaparib in advanced solid tumors. J Clin Oncol. 2020;38(15 suppl):1077–1077.
  15. Yarden Y, Sliwkowski MX. Untangling the ErbB signalling network. Nat Rev Mol Cell Biol. 2001;2:127–137.
  16. Rimawi MF, Shetty PB, Weiss HL, et al. Epidermal growth factor receptor expression in breast cancer association with biologic phenotype and clinical outcomes. Cancer. 2010;116:1234–1242.
  17. Martin V, Botta F, Zanellato E, et al. Molecular characterization of EGFR and EGFR-downstream pathways in triple negative breast carcinomas with basal like features. Histol Histopathol. 2012;27:785–792.
  18. Meseure D, Vacher S, Drak Alsibai K, et al. Profiling of EGFR mRNA and protein expression in 471 breast cancers compared with 10 normal tissues: a candidate biomarker to predict EGFR inhibitor effectiveness. Int J Cancer. 2012;131:1009–1010.
  19. Von Minckwitz G, Jonat W, Fasching P, et al. A multicentre phase II study on gefitinib in taxane- and anthracycline-pretreated metastatic breast cancer. Breast Cancer Res Treat. 2005;89:165–172.
  20. Dickler MN, Cobleigh MA, Miller KD, et al. Efficacy and safety of erlotinib in patients with locally advanced or metastatic breast cancer. Breast Cancer Res Treat. 2009;115:115–121.
  21. Nabholtz JM, Chalabi N, Radosevic-Robin N, et al. Multicentric neoadjuvant pilot phase II study of cetuximab combined with docetaxel in operable triple negative breast cancer. Int J Cancer. 2016;138:2274–2280.
  22. Bernsdorf M, Ingvar C, Jörgensen L, et al. Effect of adding gefitinib to neoadjuvant chemotherapy in estrogen receptor negative early breast cancer in a randomized phase II trial. Breast Cancer Res Treat. 2011;126:463–470.
  23. Crozier JA, Advani PP, Laplant B, et al. N0436 (Alliance): a phase II trial of Irinotecan with cetuximab in patients with metastatic breast cancer previously exposed to anthracycline and/or taxane-containing therapy. Clin Breast Cancer. 2016;16:23–30.
  24. Baselga J, Gómez P, Greil R, et al. Randomized phase II study of the anti–epidermal growth factor receptor monoclonal antibody cetuximab with cisplatin versus cisplatin alone in patients with metastatic triple-negative breast cancer. J Clin Oncol. 2013;31:2586–2592.
  25. Carey LA, Rugo HS, Marcom PK, et al. TBCRC 001: randomized phase II study of cetuximab in combination with carboplatin in stage IV triple-negative breast cancer. J Clin Oncol. 2012;30:2615–2623.
  26. Turner N, Grose R. Fibroblast growth factor signalling: from development to cancer. Nat Rev Cancer. 2010;10:116–129.
  27. Koboldt DC, Fulton RS, McLellan MD, et al. Comprehensive molecular portraits of human breast tumours. Nature. 2012;490:61–70.
  28. Turner N, Lambros MB, Horlings HM, et al. Integrative molecular profiling of triple negative breast cancers identifies amplicon drivers and potential therapeutic targets. Oncogene. 2010;29:2013–2023.
  29. Helsten T, Elkin S, Arthur E, et al. The FGFR landscape in cancer: analysis of 4,853 tumors by next-generation sequencing. Clin Cancer Res. 2016;22:259–267.
  30. Formisano L, Lu Y, Servetto A, et al. Aberrant FGFR signaling mediates resistance to CDK4/6 inhibitors in ER+ breast cancer. Nat Commun. 2019;10:1373.
  31. Hanker AB, Garrett JT, Estrada MV, et al. HER2-overexpressing breast cancers amplify FGFR signaling upon acquisition of resistance to dual therapeutic blockade of HER2. Clin Cancer Res. 2017;23:4323–4334.
  32. Soria JC, DeBraud F, Bahleda R, et al. Phase I/IIa study evaluating the safety, efficacy, pharmacokinetics, and pharmacodynamics of lucitanib in advanced solid tumors. Ann Oncol. 2014;25:2244–2251.
  33. Tabernero J, Bahleda R, Dienstmann R, et al. Phase I dose-escalation study of JNJ-42756493, an oral pan-fibroblast growth factor receptor inhibitor, in patients with advanced solid tumors. J Clin Oncol. 2015;33:3401–3408.
  34. Smyth EC, Turner NC, Peckitt C, et al. Phase II multicenter proof of concept study of AZD4547 in FGFR amplified tumours. J Clin Oncol. 2015;33(15 suppl):2508–2508.
  35. Hyman DM, Tran B, Corral Jaime J, et al. Phase Ib study of BGJ398 in combination with BYL719 in patients with select advanced solid tumors. J Clin Oncol. 2016;34(15 suppl):2500.
  36. O'Leary B, Finn RS, Turner NC. Treating cancer with selective CDK4/6 inhibitors. Nat Rev Clin Oncol. 2016;13:417–430.
  37. Asghar US, Barr AR, Cutts R, et al. Single-cell dynamics determines response to CDK4/6 inhibition in triple-negative breast cancer. Clin Cancer Res. 2017;23:5561–5572.
  38. Patel JM, Torous V, Hacker MR, et al. Retinoblastoma protein expression in triple-negative breast cancer. J Clin Oncol. 2017;35(15 suppl):1097–1097.
  39. Mitri Z, Karakas C, Wei C, et al. A phase 1 study with dose expansion of the CDK inhibitor dinaciclib (SCH 727965) in combination with epirubicin in patients with metastatic triple negative breast cancer. Invest New Drugs. 2015;33:890–894.
  40. Chien AJ, Gliwa AS, Rahmaputri S, et al. A phase Ib trial of the cyclin-dependent kinase inhibitor dinaciclib in combination with pembrolizumab in patients with advanced triple-negative breast cancer and response correlation with MYC-overexpression. J Clin Oncol. 2020;38(15 suppl):1076–1076.
  41. He S, Roberts PJ, Sorrentino JA, et al. Transient CDK4/6 inhibition protects hematopoietic stem cells from chemotherapy-induced exhaustion. Sci Transl Med. 2017;9:eaal3986.
  42. Tan AR, Wright GS, Thummala AR, et al. Trilaciclib plus chemotherapy versus chemotherapy alone in patients with metastatic triple-negative breast cancer: a multicentre, randomised, open-label, phase 2 trial. Lancet Oncol. 2019;20:1587–1601.
  43. Collins LC, Cole KS, Marotti JD, et al. Androgen receptor expression in breast cancer in relation to molecular phenotype: results from the nurses' health study. Mod Pathol. 2011;24:924–931.
  44. Rampurwala M, Wisinski KB, O'Regan R. Role of the androgen receptor in triple-negative breast cancer. Clin Adv Hematol Oncol. 2016;14:186–193.
  45. Qu Q, Mao Y, Fei XC, et al. The impact of androgen receptor expression on breast cancer survival: a retrospective study and meta-analysis. PLoS One. 2013;8:e82650.
  46. Wang C, Pan B, Zhu H, et al. Prognostic value of androgen receptor in triple negative breast cancer: a meta-analysis. Oncotarget. 2016;7:46482–46491.
  47. Gonzalez-Angulo AM, Stemke-Hale K, Palla SL, et al. Androgen receptor levels and association with PIK3CA mutations and prognosis in breast cancer. Clin Cancer Res. 2009;15:2472–2478.
  48. Hickey TE, Robinson JLL, Carroll JS, et al. Minireview: the androgen receptor in breast tissues: growth inhibitor, tumor suppressor, oncogene? Mol Endocrinol. 2012;26:1252–1267.
  49. Mufti SS, Lalkota BP, BN T, et al. Translational relevance of androgen receptor immunohistochemistry scoring systems for data harmonization in triple negative breast cancer (TNBC). J Clin Oncol. 2020;38(15 suppl):1078.
  50. Osguthorpe DJ, Hagler AT. Mechanism of androgen receptor antagonism by bicalutamide in the treatment of prostate cancer. Biochemistry. 2011;50:4105–4113.
  51. Gucalp A, Tolaney S, Isakoff SJ, et al. Phase II trial of bicalutamide in patients with androgen receptor–positive, estrogen receptor–negative metastatic breast cancer. Clin Cancer Res. 2013;19:5505–5512.
  52. Tran C, Ouk S, Clegg NJ, et al. Development of a second-generation antiandrogen for treatment of advanced prostate cancer. Science. 2009;324:787–790.
  53. Traina TA, Miller K, Yardley DA, et al. Enzalutamide for the treatment of androgen receptor–expressing triple-negative breast cancer. J Clin Oncol. 2018;36:884–890.
  54. Dent R, Schmid P, Cortes J, et al. ENDEAR: a randomized international phase 3 study comparing the efficacy and safety of enzalutamide in combination with paclitaxel chemotherapy or as monotherapy vs placebo with paclitaxel in patients with advanced diagnostic-positive triple-negative breast cancer. American Association for Cancer Research 2017, abstract OT3-02-02. Available at: https://cancerres.aacrjournals.org/content/77/4_Supplement/OT3-02-02. Accessed December 14, 2020.
  55. Traina TA, Boyle LA, Arumov A, et al. Adjuvant enzalutamide for the treatment of early-stage androgen receptor–positive TNBC. J Clin Oncol. 2019;37(15 suppl):546.
  56. Bedoya DJ, Mitsiades N. Clinical appraisal of abiraterone in the treatment of metastatic prostatic cancer: patient considerations, novel opportunities, and future directions. Onco Targets Ther. 2013;6:9–18.
  57. Bonnefoi H, Grellety T, Tredan O, et al. A phase II trial of abiraterone acetate plus prednisone in patients with triple-negative androgen receptor positive locally advanced or metastatic breast cancer (UCBG 12-1). Ann Oncol. 2016;27:812–818.
  58. Burotto M, Chiou VL, Lee JM, et al. The MAPK pathway across different malignancies: a new perspective. Cancer. 2014;120:3446–3456.
  59. Wee S, Jagani Z, Xiang KX, et al. PI3K pathway activation mediates resistance to MEK inhibitors in KRAS mutant cancers. Cancer Res. 2009;69:4286–4293.
  60. Greger JG, Eastman SD, Zhang V, et al. Combinations of BRAF, MEK, and PI3K/mTOR inhibitors overcome acquired resistance to the BRAF inhibitor GSK2118436 dabrafenib, mediated by NRAS or MEK mutations. Mol Cancer Ther. 2012;11:909–920.
  61. Jiang W, Wang X, Zhang C, et al. Expression and clinical significance of MAPK and EGFR in triple–negative breast cancer. Oncol Lett. 2020;19:1842–1848.
  62. Brufsky A, Kim S-B, Velu TJ, et al. Cobimetinib + paclitaxel as first-line treatment in patients with advanced triple-negative breast cancer: Updated results and biomarker data from the phase 2 COLET study. J Clin Oncol. 2016;34(15 suppl):1074.
  63. Brufsky A, Miles D, Zvirbule Z, et al. Cobimetinib Combined With Paclitaxel as First-Line Treatment for Patients With Advanced Triple-Negative Breast Cancer (COLET study): Primary Analysis of cohort I. 40th Annual San Antonio Breast Cancer Symposium. 2017. Abstract P5-21-01.
  64. Chumsri S, Polley M-Y, Mathur P, et al. Phase I results of the phase I/II study of pembrolizumab in combination with binimetinib in patients with unresectable locally advanced or metastatic triple-negative breast cancer. J Clin Oncol. 2020;38(5 suppl):78.
  65. Tolcher AW, Kurzrock R, Valero V, et al. Phase I dose-escalation trial of the oral AKT inhibitor uprosertib in combination with the oral MEK1/MEK2 inhibitor trametinib in patients with solid tumors. Cancer Chemother Pharmacol. 2020;85:673–683.
  66. Bedard PL, Tabernero J, Janku F, et al. A phase Ib dose-escalation study of the oral pan-PI3K inhibitor buparlisib (BKM120) in combination with the oral MEK1/2 inhibitor trametinib (GSK1120212) in patients with selected advanced solid tumors. Clin Cancer Res. 2015;21:730–738.
  67. Bardia A, Gounder M, Rodon J, et al. Phase Ib study of combination therapy with MEK inhibitor binimetinib and phosphatidylinositol 3-kinase inhibitor buparlisib in patients with advanced solid tumors with RAS/RAF alterations. Oncologist. 2020;25:e160–e169.
  68. LoRusso PM. Inhibition of the PI3K/AKT/mTOR pathway in solid tumors. J Clin Oncol. 2016;34:3803–3815.
  69. Pereira B, Chin SF, Rueda OM, et al. The somatic mutation profiles of 2,433 breast cancers refines their genomic and transcriptomic landscapes. Nat Commun. 2016;7:11479.
  70. Isakoff SJ, Infante JR, Juric D, et al. Phase Ib dose-escalation study of the Akt inhibitor ipatasertib with paclitaxel in patients with advanced solid tumors. Ann Oncol. 2014;, 4 suppl):iv148.
  71. O'Reilly KE, Rojo F, She QB, et al. mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt. Cancer Res. 2006;66:1500–1508.
  72. Wicki A, Brown N, Xyrafas A, et al. First-in human, phase 1, dose-escalation pharmacokinetic and pharmacodynamic study of the oral dual PI3K and mTORC1/2 inhibitor PQR309 in patients with advanced solid tumors (SAKK 67/13). Eur J Cancer. 2018;96:6–16.
  73. Dolly SO, Wagner AJ, Bendell JC, et al. Phase I study of apitolisib (GDC-0980), dual phosphatidylinositol-3-kinase and mammalian target of rapamycin kinase inhibitor, in patients with advanced solid tumors. Clin Cancer Res. 2016;22:2874–2884.
  74. Martín M, Chan A, Dirix L, et al. A randomized adaptive phase II/III study of buparlisib, a pan-class I PI3K inhibitor, combined with paclitaxel for the treatment of HER2- advanced breast cancer (BELLE-4). Ann Oncol. 2017;28:313–320.
  75. Leighl NB, Dent S, Clemons M, et al. A phase 2 study of perifosine in advanced or metastatic breast cancer. Breast Cancer Res Treat. 2008;108:87–92.
  76. Xing Y, Lin NU, Maurer MA, 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. 2019;21:78. Available at: https://breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-019-1154-8. Accessed December 14, 2020.
  77. Schmid P, Abraham J, Chan S, et al. Capivasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer: the PAKT trial. J Clin Oncol. 2020;38:423–433.
  78. Kim SB, Dent R, Im SA, et al. Ipatasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer (LOTUS): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 2017;18:1360–1372.
  79. Xu S, Li S, Guo Z, et al. Combined targeting of mTOR and AKT is an effective strategy for basal-like breast cancer in patient-derived xenograft models. Mol Cancer Ther. 2013;12:1665–1675.
  80. Lin J, Sampath D, Nannini MA, et al. Targeting activated Akt with GDC-0068, a novel selective Akt inhibitor that is efficacious in multiple tumor models. Clin Cancer Res. 2013;19:1760–1772.
  81. Oliveira M, Saura C, Nuciforo P, et al. FAIRLANE, a double-blind placebo-controlled randomized phase II trial of neoadjuvant ipatasertib plus paclitaxel for early triple-negative breast cancer. Ann Oncol. 2019;30:1289–1297.
  82. Dent R, M O, Isakoff S, et al. Final Results of the Double-blind Placebo-Controlled Randomised Phase II LOTUS Trial of First-Line Ipatasertib + Paclitaxel for Inoperable Locally Advanced/Metastatic Triple-Negative Breast Cancer. ESMO Virtual Congress; 2020. Abstract 1390.
  83. Schmid P, Loirat D, Savas P, et al. Phase Ib Study Evaluating a Triplet Combination of Ipatasertib, Atezolizumab, and Paclitaxel or Nab-Paclitaxel as First-Line Therapy for Locally Advanced/Metastatic Triple-Negative Breast Cancer. American Association for Cancer Research. 2019. Abstract CT049. Available at: https://cancerres.aacrjournals.org/content/79/13_Supplement/CT049. Accessed December 14, 2020.
  84. Davies BR, Greenwood H, Dudley P, et al. Preclinical pharmacology of AZD5363, an inhibitor of AKT: pharmacodynamics, antitumor activity, and correlation of monotherapy activity with genetic background. Mol Cancer Ther. 2012;11:873–887.
  85. Weiner LM, Surana R, Wang S. Monoclonal antibodies: versatile platforms for cancer immunotherapy. Nat Rev Immunol. 2010;10:317–327.
  86. Müller P, Martin K, Theurich S, et al. Microtubule-depolymerizing agents used in antibody-drug conjugates induce antitumor immunity by stimulation of dendritic cells. Cancer Immunol Res. 2014;2:741–755.
  87. Bardia A, Mayer IA, Diamond JR, et al. Efficacy & safety of anti–Trop-2 antibody drug conjugate sacituzumab govitecan (IMMU-132) in heavily pretreated patients with metastatic triple-negative breast cancer. J Clin Oncol. 2017;35:2141–2148.
  88. Trerotola M, Cantanelli P, Guerra E, et al. Upregulation of Trop-2 quantitatively stimulates human cancer growth. Oncogene. 2013;32:222–233. Available at: http://dx.doi.org/10.1038/onc.2012.36. Accessed December 14, 2020. [DOI: 10.1038/onc.2012.36]
  89. Ambrogi F, Fornili M, Boracchi P, et al. Trop-2 is a determinant of breast cancer survival. PLoS One. 2014;9:e96993.
  90. Bardia A, Mayer IA, Vahdat LT, et al. Sacituzumab govitecan-hziy in refractory metastatic triple-negative breast cancer. N Engl J Med. 2019;380:741–751.
  91. Bardia A, Tolaney SM, Loirat D, et al. ASCENT: A Randomized Phase III Study of Sacituzumab Govitecan vs Treatment of Physician's Choice in Patients With Previously Treated Metastatic Triple Negative Breast Cancer. European Society of Medical Oncology [Virtual]; 2020.
  92. Lisberg AE, Sands J, Shimizu T, et al. Dose escalation and expansion from the phase I study of DS-1062, a trophoblast cell-surface antigen 2 (TROP2) antibody drug conjugate, in patients with advanced non–small cell lung cancer. J Clin Oncol. 2020;38(15 suppl):9619.
  93. Taylor KM, Morgan HE, Johnson A, et al. Structure-function analysis of LIV-1, the breast cancer–associated protein that belongs to a new subfamily of zinc transporters. Biochem J. 2003;375:51–59.
  94. Sussman D, Smith LM, Anderson ME, et al. SGN-LIV1A: a novel antibody-drug conjugate targeting LIV-1 for the treatment of metastatic breast cancer. Mol Cancer Ther. 2014;13:2991–3000.
  95. Modi S, Pusztai L, Forero A, et al. Phase 1 Study of the Antibody-Drug Conjugate SGN-LIV1A in Patients With Heavily Pretreated Triple-Negative Metastatic Breast Cancer. 40th Annual San Antonio Breast Cancer Symposium. 2017. Abstract PD3-14.
  96. Han HS, Alemany CA, Brown-Glaberman UA, et al. SGNLVA-002: single-arm, open label phase Ib/II study of ladiratuzumab vedotin in combination with pembrolizumab for first-line treatment of patients with unresectable locally advanced or metastatic triple-negative breast cancer. J Clin Oncol. 2019;37(15 suppl):TPS1110.
  97. Yardley DA, Abu-Kalaf M, Boni V, et al. MORPHEUS: A Phase Ib/II Trial Platform Evaluating the Safety and Efficacy of Multiple Cancer Immunotherapy Combinations in Patients With Hormone Receptor–Positive and Triple-Negative Breast Cancer. 41st Annual San Antonio Breast Cancer Symposium. 2018. Abstract OT2-06-04.
  98. Rose AAN, Grosset AA, Dong Z, et al. Glycoprotein nonmetastatic b is an independent prognostic indicator of recurrence and a novel therapeutic target in breast cancer. Clin Cancer Res. 2010;16:2147–2156.
  99. Maric G, Annis MG, Dong Z, et al. GPNMB cooperates with neuropilin-1 to promote mammary tumor growth and engages integrin α5β1 for efficient breast cancer metastasis. Oncogene. 2015;34:5494–5504.
  100. Maric G, Rose AAN, Annis MG, et al. Glycoprotein non-metastatic b (GPNMB): a metastatic mediator and emerging therapeutic target in cancer. Onco Targets Ther. 2013;6:839–852.
  101. Bendell J, Saleh M, Rose AAN, et al. Phase I/II study of the antibody-drug conjugate glembatumumab vedotin in patients with locally advanced or metastatic breast cancer. J Clin Oncol. 2014;32:3619–3625.
  102. Yardley DA, Weaver R, Melisko ME, et al. EMERGE: a randomized phase II study of the antibody-drug conjugate glembatumumab vedotin in advanced glycoprotein NMB-expressing breast cancer. J Clin Oncol. 2015;33:1609–1619.
  103. Vahdat LT, Forero-Torres A, Schmid P, et al. METRIC: A Randomized International Phase 2b Study of the Antibody-Drug Conjugate Glembatumumab Vedotin in gpNMB-Overexpressing, Metastatic, Triple-Negative Breast Cancer. 40th Annual San Antonio Breast Cancer Symposium. 2018. Abstract P6-20-01.
  104. Müller P, Kreuzaler M, Khan T, et al. Trastuzumab emtansine (T-DM1) renders HER2+ breast cancer highly susceptible to CTLA-4/PD-1 blockade. Sci Transl Med. 2015;7:315ra188.
  105. Cardillo TM, Sharkey RM, Rossi DL, et al. Synthetic lethality exploitation by an anti–Trop-2-SN-38 antibody-drug conjugate, IMMU-132, plus PARP inhibitors in BRCA1/2–wild-type triple-negative breast cancer. Clin Cancer Res. 2017;23:3405–3415.
  106. Shen Y, Zhang W, Liu J, et al. Therapeutic activity of DCC-2036, a novel tyrosine kinase inhibitor, against triple-negative breast cancer patient–derived xenografts by targeting AXL/MET. Int J Cancer. 2019;144:651–664.
  107. Dunn SE, Jayanthan A, Huynh M, et al. PMD-026, A First-in-Class Oral p90 Ribosomal S6 kinase (RSK) Inhibitor for Triple Negative Breast Cancer (TNBC). American Association for Cancer Research; 2020. Abstract P3-10-10. Available at: https://cancerres.aacrjournals.org/content/80/4_Supplement/P3-10-10. Accessed December 14, 2020.
  108. Beeram M, Wang JS-Z, Mina LA, et al. First-in-human phase I/Ib multicenter, open-label dose escalation study to assess safety and tolerability of PMD-026 in patients with metastatic breast cancer with expansion in metastatic triple negative breast cancer. J Clin Oncol. 2020;38(15 suppl):TPS1110.
  109. Yam C, Rauch GM, Rahman T, et al. A phase II study of mirvetuximab soravtansine in triple-negative breast cancer. Invest New Drugs. 2020.

MeSH Term

Antibodies, Monoclonal, Humanized
Female
Humans
Immunoconjugates
Phosphoinositide-3 Kinase Inhibitors
Triple Negative Breast Neoplasms

Chemicals

Antibodies, Monoclonal, Humanized
Immunoconjugates
Phosphoinositide-3 Kinase Inhibitors
Journal Article Review

Word Cloud

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