Overview on Current Trends and Emerging Therapies in the Chemotherapy of Patients with Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer
Trends and Emerging Therapies in Chemotherapy of HER2-positive BC
DOI:
https://doi.org/10.31661/gmj.v12i.3021Keywords:
HER2-positive; Breast Cancer; Chemotherapy; Targeted Therapies; Combination Treatment; Immune Checkpoint InhibitorsAbstract
Over the past few decades, significant progress has been made in the management of hu-man epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) due to the de-velopment of targeted therapies. However, HER2-positive BC is an aggressive subtype, posing significant challenges, including treatment resistance and disease recurrence. Cur-rent standard treatment options for HER2-positive BC include combinations of chemother-apy drugs, targeted therapies such as trastuzumab and pertuzumab, and hormone therapies. However, some important limitations of these treatments, such as resistance and adverse effects, are reported. Also, we showed emerging therapeutic options, such as novel chemo-therapy agents, antibody-drug conjugates, and immune checkpoint inhibitors, and discussed their mechanisms of action, potential benefits, and potential future directions in the field.
References
Mirmalek SA, Faraji S, Ranjbaran S, Aryan H, Arani HZ, Jangholi E, Marzouni HZ, Salimi-Tabatabaee SA. Cyanidin 3-glycoside induced apoptosis in MCF-7 breast cancer cell line. Archives of Medical Science: AMS. 2023;19(4):1092.
Iacopetta D, Ceramella J, Baldino N, Sinicropi MS, Catalano A. Targeting breast cancer: An overlook on current strategies. International Journal of Molecular Sciences. 2023 Feb 11;24(4):3643.
https://doi.org/10.3390/ijms24043643
Johnston SR, Hegg R, Im SA, Park IH, Burdaeva O, Kurteva G, Press MF, Tjulandin S, Iwata H, Simon SD, Kenny S. Phase III, randomized study of dual human epidermal growth factor receptor 2 (HER2) blockade with lapatinib plus trastuzumab in combination with an aromatase inhibitor in postmenopausal women with HER2-positive, hormone receptor-positive metastatic breast cancer: updated results of ALTERNATIVE. Journal of Clinical Oncology. 2021 Jan 1;39(1):79-89.
https://doi.org/10.1200/JCO.20.01894
Majumder A, Sandhu M, Banerji D, Steri V, Olshen A, Moasser MM. The role of HER2 and HER3 in HER2-amplified cancers beyond breast cancers. Scientific reports. 2021 Apr 27;11(1):9091.
https://doi.org/10.1038/s41598-021-88683-w
Gupta R, Gupta S, Antonios B, Ghimire B, Jindal V, Deol J, Gaikazian S, Huben M, Anderson J, Stender M, Jaiyesimi I. Therapeutic landscape of advanced HER2-positive breast cancer in 2022. Medical Oncology. 2022 Oct 12;39(12):258.
https://doi.org/10.1007/s12032-022-01849-y
Wu X, Yang H, Yu X, Qin JJ. Drug-resistant HER2-positive breast cancer: Molecular mechanisms and overcoming strategies. Frontiers in Pharmacology. 2022 Sep 23;13:1012552.
https://doi.org/10.3389/fphar.2022.1012552
Kunte S, Abraham J, Montero AJ. Novel HER2-targeted therapies for HER2-positive metastatic breast cancer. Cancer. 2020 Oct 1;126(19):4278-88.
https://doi.org/10.1002/cncr.33102
Mitani S, Kawakami H. Emerging targeted therapies for HER2 positive gastric cancer that can overcome trastuzumab resistance. Cancers. 2020 Feb 10;12(2):400.
https://doi.org/10.3390/cancers12020400
Abe T, Sagara A, Okada D, Matsuzaka K. Safety survey on infusion reaction and cardiac dysfunction when switching from reference trastuzumab (HERCEPTIN®) to biosimilar trastuzumab (Trastuzumab NK) in the treatment of HER2 positive breast cancer. Molecular and clinical oncology. 2023 May 1;18(5):1-5.
https://doi.org/10.3892/mco.2023.2637
Hunter FW, Barker HR, Lipert B, Rothé F, Gebhart G, Piccart-Gebhart MJ, Sotiriou C, Jamieson SM. Mechanisms of resistance to trastuzumab emtansine (T-DM1) in HER2-positive breast cancer. British journal of cancer. 2020 Mar 3;122(5):603-12.
https://doi.org/10.1038/s41416-019-0635-y
Spring LM, Clark SL, Li T, Goel S, Tayob N, Viscosi E, Abraham E, Juric D, Isakoff SJ, Mayer E, Moy B. Phase 1b clinical trial of ado-trastuzumab emtansine and ribociclib for HER2-positive metastatic breast cancer. NPJ Breast Cancer. 2021 Aug 4;7(1):103.
https://doi.org/10.1038/s41523-021-00311-y
Tolaney SM, Tayob N, Dang C, Yardley DA, Isakoff SJ, Valero V, Faggen M, Mulvey T, Bose R, Hu J, Weckstein D. Adjuvant trastuzumab emtansine versus paclitaxel in combination with trastuzumab for stage I HER2-positive breast cancer (ATEMPT): a randomized clinical trial. Journal of Clinical Oncology. 2021 Jul 20;39(21):2375-85.
https://doi.org/10.1200/JCO.20.03398
Kulukian A, Lee P, Taylor J, Rosler R, de Vries P, Watson D, Forero-Torres A, Peterson S. Preclinical activity of HER2-selective tyrosine kinase inhibitor tucatinib as a single agent or in combination with trastuzumab or docetaxel in solid tumor models. Molecular Cancer Therapeutics. 2020 Apr 1;19(4):976-87.
https://doi.org/10.1158/1535-7163.MCT-19-0873
Collins DM, Conlon NT, Kannan S, Verma CS, Eli LD, Lalani AS, Crown J. Preclinical characteristics of the irreversible pan-HER kinase inhibitor neratinib compared with lapatinib: implications for the treatment of HER2-positive and HER2-mutated breast cancer. Cancers. 2019 May 28;11(6):737.
https://doi.org/10.3390/cancers11060737
Saura C, Oliveira M, Feng YH, Dai MS, Chen SW, Hurvitz SA, Kim SB, Moy B, Delaloge S, Gradishar W, Masuda N. Neratinib plus capecitabine versus lapatinib plus capecitabine in HER2-positive metastatic breast cancer previously treated with≥ 2 HER2-directed regimens: phase III NALA trial. Journal of Clinical Oncology. 2020 Sep 9;38(27):3138.
https://doi.org/10.1200/JCO.20.00147
Holmes FA, Moy B, Delaloge S, Chia SK, Ejlertsen B, Mansi J, Iwata H, Gnant M, Buyse M, Barrios CH, Silovski T. Overall survival with neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): A randomised, double-blind, placebo-controlled, phase 3 trial. European Journal of Cancer. 2023 May 1;184:48-59.
https://doi.org/10.1016/j.ejca.2023.02.002
Iwata H, Masuda N, Kim SB, Inoue K, Rai Y, Fujita T, Chiu J, Ohtani S, Takahashi M, Miyaki T, Lu YS. Neratinib after trastuzumab-based adjuvant therapy in patients from Asia with early stage HER2-positive breast cancer. Future oncology. 2019 May;15(21):2489-501.
https://doi.org/10.2217/fon-2019-0143
Lin NU. Tucatinib Plus Trastuzumab and Capecitabine for ERBB2 (HER2)-Positive Metastatic Breast Cancer With Brain Metastases-Reply. JAMA oncology. 2023 Jul 1;9(7):1009-.
https://doi.org/10.1001/jamaoncol.2023.1391
Murthy RK, Loi S, Okines A, Paplomata E, Hamilton E, Hurvitz SA, Lin NU, Borges V, Abramson V, Anders C, Bedard PL. Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer. New England Journal of Medicine. 2020 Feb 13;382(7):597-609.
https://doi.org/10.1056/NEJMoa1914609
Hurvitz SA, Kalinsky K, Tripathy D, Sledge G, Gradishar WJ, O'Shaughnessy J, Modi S, Park H, McCartney A, Frentzas S, Shannon C. 273TiP ACE-Breast-03: A phase II study patients with HER2-positive metastatic breast cancer whose disease is resistant or refractory to T-DM1, and/or T-DXd, and/or tucatinib-containing regimens treated with ARX788. Annals of Oncology. 2022 Sep 1;33:S662-3.
https://doi.org/10.1016/j.annonc.2022.07.1857
Corti C, Criscitiello C. Tucatinib approval by EMA expands options for HER2-positive locally advanced or metastatic breast cancer. ESMO open. 2021;6(2):7029.
https://doi.org/10.1016/j.esmoop.2021.100063
Zhang J, Ji D, Cai L, Yao H, Yan M, Wang X, Shen W, Du Y, Pang H, Lai X, Zeng H. First-in-human HER2-targeted bispecific antibody KN026 for the treatment of patients with HER2-positive metastatic breast cancer: results from a phase I study. Clinical Cancer Research. 2022 Feb 15;28(4):618-28.
https://doi.org/10.1158/1078-0432.CCR-21-2827
Geyer Jr CE, Untch M, Prat A, Rastogi P, Niikura N, Mathias E, McLean LA, Wang Y, Loibl S. Abstract OT-03-01: trastuzumab deruxtecan (T-DXd; DS-8201) vs trastuzumab emtansine (T-DM1) in high-risk patients with HER2-positive, residual invasive early breast cancer after neoadjuvant therapy: a randomized, phase 3 trial (DESTINY-Breast05). Cancer Research. 2021 Feb 15;81(4_Supplement):OT-03.
https://doi.org/10.1158/1538-7445.SABCS20-OT-03-01
Batista MV, Pérez-Garcia JM, Cussac AL, Cortez P, Borrego MR, De La Haba J, Cejalvo JM, Racca F, Servitja S, Blanch S, Lema L. 330TiP Trastuzumab deruxtecan (T-DXd; DS-8201) in HER2-positive (HER2+) and HER2-low expressing (HER-LE) metastatic breast cancer (MBC) with brain metastases (BM) and/or leptomeningeal carcinomatosis (LMC): DEBBRAH. Annals of Oncology. 2021 Sep 1;32:S509-10.
https://doi.org/10.1016/j.annonc.2021.08.613
Lee J, Park YH. Trastuzumab deruxtecan for HER2+ advanced breast cancer. Future Oncology. 2021 Oct;18(1):7-19.
https://doi.org/10.2217/fon-2021-0550
Krasniqi E, Barchiesi G, Pizzuti L, Mazzotta M, Venuti A, Maugeri-Saccà M, Sanguineti G, Massimiani G, Sergi D, Carpano S, Marchetti P. Immunotherapy in HER2-positive breast cancer: state of the art and future perspectives. Journal of hematology & oncology. 2019 Dec;12(1):1-26.
https://doi.org/10.1186/s13045-019-0798-2
Högner A, Moehler M. Immunotherapy in gastric cancer. Current Oncology. 2022 Mar 2;29(3):1559-74.
https://doi.org/10.3390/curroncol29030131
Zhao S, Xian X, Tian P, Li W, Wang K, Li Y. Efficacy of combination chemo-immunotherapy as a first-line treatment for advanced non-small-cell lung cancer patients with HER2 alterations: a case series. Frontiers in Oncology. 2021 Apr 20;11:633522.
https://doi.org/10.3389/fonc.2021.633522
Arab A, Yazdian-Robati R, Behravan J. HER2-positive breast cancer immunotherapy: A focus on vaccine development. Archivum immunologiae et therapiae Experimentalis. 2020 Feb;68:1-8.
https://doi.org/10.1007/s00005-019-00566-1
Liang Y, Liu X, Li K, Li H. Current situation of programmed cell death protein 1/programmed cell death ligand 1 inhibitors in advanced triple-negative breast cancer. Chinese Journal of Cancer Research. 2022 Apr 4;34(2):117.
https://doi.org/10.21147/j.issn.1000-9604.2022.02.07
Loi S, Giobbie-Hurder A, Gombos A, Bachelot T, Hui R, Curigliano G, Campone M, Biganzoli L, Bonnefoi H, Jerusalem G, Bartsch R. Pembrolizumab plus trastuzumab in trastuzumab-resistant, advanced, HER2-positive breast cancer (PANACEA): a single-arm, multicentre, phase 1b-2 trial. The Lancet Oncology. 2019 Mar 1;20(3):371-82.
Emens LA, Esteva FJ, Beresford M, Saura C, De Laurentiis M, Kim SB, Im SA, Wang Y, Salgado R, Mani A, Shah J. Trastuzumab emtansine plus atezolizumab versus trastuzumab emtansine plus placebo in previously treated, HER2-positive advanced breast cancer (KATE2): a phase 2, multicentre, randomised, double-blind trial. The lancet oncology. 2020 Oct 1;21(10):1283-95.
https://doi.org/10.1016/S1470-2045(20)30465-4
Chia S, Bedard PL, Hilton J, Amir E, Gelmon K, Goodwin R, Villa D, Cabanero M, Tu D, Tsao M, Seymour L. A phase Ib trial of durvalumab in combination with trastuzumab in HER2-positive metastatic breast cancer. The Oncologist. 2019;24(11):1439-45.
https://doi.org/10.1634/theoncologist.2019-0321
Solinas C, Fumagalli D, Dieci MV. Immune checkpoint blockade in HER2-positive breast cancer: what role in early disease setting?. Cancers. 2021 Apr 1;13(7):1655.
https://doi.org/10.3390/cancers13071655
Agostinetto E, Montemurro F, Puglisi F, Criscitiello C, Bianchini G, Del Mastro L, Introna M, Tondini C, Santoro A, Zambelli A. Immunotherapy for HER2-positive breast cancer: clinical evidence and future perspectives. Cancers. 2022 Apr 25;14(9):2136.
https://doi.org/10.3390/cancers14092136
Matusz-Fisher A, Tan AR. Combination of HER2-targeted agents with immune checkpoint inhibitors in the treatment of HER2-positive breast cancer. Expert Opinion on Biological Therapy. 2022 Mar 4;22(3):385-95.
https://doi.org/10.1080/14712598.2021.1981284
Li L, Zhang D, Liu B, Lv D, Zhai J, Guan X, Yi Z, Ma F. Antibody-drug conjugates in HER2-positive breast cancer. Chinese medical journal. 2022 Feb 5;135(03):261-7.
https://doi.org/10.1097/CM9.0000000000001932
Jacobson A. Trastuzumab deruxtecan improves progression-free survival and intracranial response in patients with HER2-positive metastatic breast cancer and brain metastases. The Oncologist. 2022 Mar 1;27(Supplement_1):S3-4.
https://doi.org/10.1093/oncolo/oyac009
Pallerla S, Abdul AU, Comeau J, Jois S. Cancer vaccines, treatment of the future: with emphasis on HER2-positive breast cancer. International journal of molecular sciences. 2021 Jan 14;22(2):779.
https://doi.org/10.3390/ijms22020779
Swain SM, Shastry M, Hamilton E. Targeting HER2-positive breast cancer: Advances and future directions. Nature Reviews Drug Discovery. 2023 Feb;22(2):101-26.
https://doi.org/10.1038/s41573-022-00579-0
Duro-Sánchez S, Alonso MR, Arribas J. Immunotherapies against HER2-Positive Breast Cancer. Cancers. 2023 Feb 8;15(4):1069.
https://doi.org/10.3390/cancers15041069
Pernas S, Tolaney SM. Clinical trial data and emerging strategies: HER2-positive breast cancer. Breast Cancer Research and Treatment. 2022 Jun;193(2):281-91.
https://doi.org/10.1007/s10549-022-06575-7
Dees S, Ganesan R, Singh S, Grewal IS. Emerging CAR-T cell therapy for the treatment of triple-negative breast cancer. Molecular cancer therapeutics. 2020 Dec 1;19(12):2409-21.
https://doi.org/10.1158/1535-7163.MCT-20-0385
Schettini F, Barbao P, Brasó-Maristany F, Galván P, Martínez D, Paré L, De Placido S, Prat A, Guedan S. Identification of cell surface targets for CAR-T cell therapies and antibody-drug conjugates in breast cancer. ESMO open. 2021 Jun 1;6(3):100102.
https://doi.org/10.1016/j.esmoop.2021.100102
Fujimoto Y, Morita TY, Ohashi A, Haeno H, Hakozaki Y, Fujii M, Kashima Y, Kobayashi SS, Mukohara T. Combination treatment with a PI3K/Akt/mTOR pathway inhibitor overcomes resistance to anti-HER2 therapy in PIK3CA-mutant HER2-positive breast cancer cells. Scientific reports. 2020 Dec 10;10(1):21762.
https://doi.org/10.1038/s41598-020-78646-y
Wang J, Xu B. Targeted therapeutic options and future perspectives for HER2-positive breast cancer. Signal transduction and targeted therapy. 2019 Sep 13;4(1):34.
https://doi.org/10.1038/s41392-019-0069-2
Ayoub NM, Al-Shami KM, Yaghan RJ. Immunotherapy for HER2-positive breast cancer: recent advances and combination therapeutic approaches. Breast Cancer: Targets and Therapy. 2019 Jan 17:53-69.
https://doi.org/10.2147/BCTT.S175360
Azgahdi S, Candas D, Xie B, Zhang L, Zhang Y, Fan M, Liu L, Sweeney C, Pan CX, Ozpiskin O, Vaughan A. Dual Blockade of CD47 and HER2 Re-sensitizes Resistant Breast Cancer Cells to Radiation Therapy. International Journal of Radiation Oncology, Biology, Physics. 2019 Sep 1;105(1):E39.
https://doi.org/10.1016/j.ijrobp.2019.06.705
You KS, Yi YW, Cho J, Seong YS. Dual inhibition of AKT and MEK pathways potentiates the anti-cancer effect of gefitinib in triple-negative breast cancer cells. Cancers. 2021 Mar 10;13(6):1205.
https://doi.org/10.3390/cancers13061205
Walshe JM, Denduluri N, Berman AW, Rosing DR, Swain SM. A phase II trial with trastuzumab and pertuzumab in patients with HER2-overexpressed locally advanced and metastatic breast cancer. Clinical breast cancer. 2006 Feb 1;6(6):535-9.
https://doi.org/10.3816/CBC.2006.n.009
Fischgräbe J, Götte M, Michels K, Kiesel L, Wülfing P. Targeting endothelin A receptor enhances anti-proliferative and anti-invasive effects of the HER2 antibody trastuzumab in HER2-overexpressing breast cancer cells. International journal of cancer. 2010 Aug 1;127(3):696-706.
https://doi.org/10.1002/ijc.25076
Siddique AB, Ebrahim H, Mohyeldin M, Jois SD, Sayed KA. The olive-based oleocanthal as a dual HER2-MET inhibitor for the control of breast cancer recurrence. Cancer Research. 2018 Jul 1;78(13_Supplement):2683-.
https://doi.org/10.1158/1538-7445.AM2018-2683
Callahan R, Hurvitz S. HER2-positive breast cancer: current management of early, advanced, and recurrent disease. Current opinion in obstetrics & gynecology. 2011 Feb;23(1):37.
https://doi.org/10.1097/GCO.0b013e3283414e87
Loibl S, Gianni L. HER2-positive breast cancer. The Lancet. 2017 Jun 17;389(10087):2415-29.
https://doi.org/10.1016/S0140-6736(16)32417-5
Chen B, Zhang G, Wei G, Wang Y, Guo L, Lin J, Li K, Mok H, Cao L, Ren C, Wen L. Heterogeneity of genomic profile in patients with HER2-positive breast cancer. Endocrine-related cancer. 2020 Mar 1;27(3):153-62.
https://doi.org/10.1530/ERC-19-0414
Huang RS, Li X, Haberberger J, Sokol E, Severson E, Duncan DL, Hemmerich A, Edgerly C, Williams E, Elvin J, Vergilio JA. Biomarkers in breast cancer: An integrated analysis of comprehensive genomic profiling and Pd-L1 immunohistochemistry biomarkers in 312 patients with breast cancer. The oncologist. 2020 Nov 1;25(11):943-53.
https://doi.org/10.1634/theoncologist.2020-0449
Curtis C. Genomic profiling of breast cancers. Current opinion in obstetrics & gynecology. 2015 Feb;27(1):34.
https://doi.org/10.1097/GCO.0000000000000145
Von Minckwitz G, Procter M, De Azambuja E, Zardavas D, Benyunes M, Viale G, Suter T, Arahmani A, Rouchet N, Clark E, Knott A. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. New England Journal of Medicine. 2017 Jul 13;377(2):122-31.
https://doi.org/10.1056/NEJMoa1703643
Capelan M, Pugliano L, De Azambuja E, Bozovic I, Saini KS, Sotiriou C, Loi S, Piccart-Gebhart MJ. Pertuzumab: new hope for patients with HER2-positive breast cancer. Annals of oncology. 2013 Feb 1;24(2):273-82.
https://doi.org/10.1093/annonc/mds328
Watanabe S, Yonesaka K, Tanizaki J, Nonagase Y, Takegawa N, Haratani K, Kawakami H, Hayashi H, Takeda M, Tsurutani J, Nakagawa K. Targeting of the HER2/HER3 signaling axis overcomes ligand-mediated resistance to trastuzumab in HER2-positive breast cancer. Cancer Medicine. 2019 Mar;8(3):1258-68.
https://doi.org/10.1002/cam4.1995
Vu T, Sliwkowski MX, Claret FX. Personalized drug combinations to overcome trastuzumab resistance in HER2-positive breast cancer. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer. 2014 Dec 1;1846(2):353-65.
https://doi.org/10.1016/j.bbcan.2014.07.007
Cho SH, Jeon J, Kim SI. Personalized medicine in breast cancer: a systematic review. Journal of breast cancer. 2012 Sep 1;15(3):265-72.
https://doi.org/10.4048/jbc.2012.15.3.265
Goutsouliak K, Veeraraghavan J, Sethunath V, De Angelis C, Osborne CK, Rimawi MF, Schiff R. Towards personalized treatment for early stage HER2-positive breast cancer. Nature Reviews Clinical Oncology. 2020 Apr;17(4):233-50.
https://doi.org/10.1038/s41571-019-0299-9
De Abreu FB, Wells WA, Tsongalis GJ. The emerging role of the molecular diagnostics laboratory in breast cancer personalized medicine. The American journal of pathology. 2013 Oct 1;183(4):1075-83.
Published
How to Cite
Issue
Section
License
Copyright (c) 2023 Galen Medical Journal
This work is licensed under a Creative Commons Attribution 4.0 International License.
