Fu Z, Li S, Han S, Shi C, Zhang Y. Antibody drug conjugate: the “biological missile” for targeted cancer therapy. Signal Transduct Target Ther. 2022;7(1):93. https://doi.org/10.1038/s41392-022-00947-7.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Khongorzul P, Ling CJ, Khan FU, Ihsan AU, Zhang J. Antibody-Drug Conjugates: A Comprehensive Review. Mol Cancer Res. 2020;18(1):3–19. https://doi.org/10.1158/1541-7786.Mcr-19-0582.

Article  CAS  PubMed  Google Scholar 

Xiao T, Ali S, Mata D, Lohmann AE, Blanchette PS. Antibody-drug conjugates in breast cancer: Ascent to destiny and beyond-A 2023 review. Curr Oncol. 2023;30(7):6447–61. https://doi.org/10.3390/curroncol30070474.

Article  PubMed  PubMed Central  Google Scholar 

Peddi PF, Hurvitz SA. Trastuzumab emtansine: the first targeted chemotherapy for treatment of breast cancer. Future Oncol. 2013;9(3):319–26. https://doi.org/10.2217/fon.13.7.

Article  CAS  PubMed  Google Scholar 

Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga J, et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med. 2012;367(19):1783–91. https://doi.org/10.1056/NEJMoa1209124.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Perez EA, Barrios C, Eiermann W, Toi M, Im YH, Conte P, et al. Trastuzumab emtansine with or without pertuzumab versus trastuzumab with taxane for human epidermal growth factor receptor 2-positive advanced breast cancer: Final results from MARIANNE. Cancer. 2019;125(22):3974–84. https://doi.org/10.1002/cncr.32392.

Article  CAS  PubMed  Google Scholar 

Ogitani Y, Hagihara K, Oitate M, Naito H, Agatsuma T. Bystander killing effect of DS-8201a, a novel anti-human epidermal growth factor receptor 2 antibody-drug conjugate, in tumors with human epidermal growth factor receptor 2 heterogeneity. Cancer Sci. 2016;107(7):1039–46. https://doi.org/10.1111/cas.12966.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Modi S, Saura C, Yamashita T, Park YH, Kim SB, Tamura K, et al. Trastuzumab deruxtecan in previously treated HER2-positive breast cancer. N Engl J Med. 2020;382(7):610–21. https://doi.org/10.1056/NEJMoa1914510.

Article  CAS  PubMed  Google Scholar 

Hurvitz SA, Hegg R, Chung WP, Im SA, Jacot W, Ganju V, et al. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: updated results from DESTINY-Breast03, a randomised, open-label, phase 3 trial. Lancet. 2023;401(10371):105–17. https://doi.org/10.1016/s0140-6736(22)02420-5.

Article  CAS  PubMed  Google Scholar 

Cortés J, Hurvitz SA, Im S-A, Iwata H, Curigliano G, Kim S-B, et al. Trastuzumab deruxtecan versus trastuzumab emtansine in HER2-positive metastatic breast cancer: long-term survival analysis of the DESTINY-Breast03 trial. Nat Med. 2024;30(8):2208–15. https://doi.org/10.1038/s41591-024-03021-7.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Andre F. DESTINY-Breast07: Dose-expansion interim analysis of T-DXd monotherapy and T-DXd + pertuzumab in patients with previously untreated HER2+ mBC. J Clin Oncol. 2024;42(16):1009.

Article  Google Scholar 

Tolaney SM, Barroso-Sousa R, Jiang Z, Park YH, Rimawi M, Saura Manich C, et al. 328TiP Phase III study of trastuzumab deruxtecan (T-DXd) with or without pertuzumab vs a taxane, trastuzumab and pertuzumab in first-line (1L), human epidermal growth factor receptor 2–positive (HER2+) metastatic breast cancer (mBC): DESTINY-Breast09. Ann Oncol. 2021;32:S507–8. https://doi.org/10.1016/j.annonc.2021.08.611.

Article  Google Scholar 

Holthuis EI, Vondeling GT, Kuiper JG, Dezentjé V, Rosenlund M, Overbeek JA, et al. Real-world data of HER2-low metastatic breast cancer: A population based cohort study. Breast. 2022;66:278–84. https://doi.org/10.1016/j.breast.2022.11.003.

Article  PubMed  PubMed Central  Google Scholar 

Modi S, Jacot W, Yamashita T, Sohn J, Vidal M, Tokunaga E, et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med. 2022;387(1):9–20. https://doi.org/10.1056/NEJMoa2203690.

Article  CAS  PubMed  PubMed Central  Google Scholar 

FDA approves fam-trastuzumab deruxtecan-nxki for HER2-low breast cancer. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-fam-trastuzumab-deruxtecan-nxki-her2-low-breast-cancer. Accessed 8 May 2022

Franchina M, Pizzimenti C, Fiorentino V, Martini M, Ricciardi GRR, Silvestris N, et al. Low and ultra-low HER2 in human breast cancer: An effort to define new neoplastic subtypes. Int J Mol Sci. 2023;24(16):12795. https://doi.org/10.3390/ijms241612795.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bardia A, Hu X, Dent R, Yonemori K, Barrios CH, O’Shaughnessy JA, et al. Trastuzumab deruxtecan after endocrine therapy in metastatic breast cancer. N Engl J Med. 2024. https://doi.org/10.1056/NEJMoa2407086.

Article  PubMed  Google Scholar 

Cameron DAA, Jacot W, Yamashita T, Losada MJV, Schmid P, Lee KS, et al. DESTINY-Breast04 subgroup analyses of trastuzumab deruxtecan (T-DXd) vs treatment of physician’s choice (TPC) in patients (pts) with human epidermal growth factor 2 (HER2)-low, estrogen-receptor (ER) expression immunohistochemistry (IHC) 0-10% metastatic breast cancer (mBC). ESMO Open. 2023;8(1):101381. https://doi.org/10.1016/j.esmoop.2023.101381.

Article  Google Scholar 

Mosele F, Deluche E, Lusque A, Le Bescond L, Filleron T, Pradat Y, et al. Trastuzumab deruxtecan in metastatic breast cancer with variable HER2 expression: the phase 2 DAISY trial. Nat Med. 2023;29(8):2110–20. https://doi.org/10.1038/s41591-023-02478-2.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Tarantino P, Gandini S, Nicolò E, Trillo P, Giugliano F, Zagami P, et al. Evolution of low HER2 expression between early and advanced-stage breast cancer. Eur J Cancer. 2022;163:35–43. https://doi.org/10.1016/j.ejca.2021.12.022.

Article  CAS  PubMed  Google Scholar 

Geukens T, De Schepper M, Richard F, Maetens M, Van Baelen K, Mahdami A, et al. Intra-patient and inter-metastasis heterogeneity of HER2-low status in metastatic breast cancer. Eur J Cancer. 2023;188:152–60. https://doi.org/10.1016/j.ejca.2023.04.026.

Article  CAS  PubMed  Google Scholar 

Tarantino P, Hughes M, Kusmick R, Alder L, Pereslete A, Noteware L, et al. Abstract PS08–09: Impact of HER2 expression dynamics on the real-world activity of trastuzumab deruxtecan for metastatic breast cancer (RELIEVE). Cancer Res. 2024;84(9_Supplement):PS08-9–9-PS-9. https://doi.org/10.1158/1538-7445.SABCS23-PS08-09.

Article  Google Scholar 

Kopp A, Hofsess S, Cardillo TM, Govindan SV, Donnell J, Thurber GM. Antibody-drug conjugate sacituzumab govitecan drives efficient tissue penetration and rapid intracellular drug release. Mol Cancer Ther. 2023;22(1):102–11. https://doi.org/10.1158/1535-7163.Mct-22-0375.

Article  CAS  PubMed  Google Scholar 

Rugo HS, Bardia A, Marmé F, Cortes J, Schmid P, Loirat D, et al. Sacituzumab govitecan in hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer. J Clin Oncol. 2022;40(29):3365–76. https://doi.org/10.1200/jco.22.01002.

Article  CAS  PubMed  Google Scholar 

Rugo HS, Bardia A, Marmé F, Cortés J, Schmid P, Loirat D, et al. Overall survival with sacituzumab govitecan in hormone receptor-positive and human epidermal growth factor receptor 2-negative metastatic breast cancer (TROPiCS-02): a randomised, open-label, multicentre, phase 3 trial. The Lancet. 2023;402(10411):1423–33. https://doi.org/10.1016/S0140-6736(23)01245-X.

Article  CAS  Google Scholar 

Jhaveri K, André F, Hamilton E, Schmid P, Anders C, Testa L, et al. Abstract RF02–03: Trastuzumab deruxtecan (T-DXd) in combination with anastrozole or fulvestrant in patients with HER2-low HR+ advanced/metastatic breast cancer: a Phase 1b, open-label, multicenter, dose-expansion study (DESTINY-Breast08). Cancer Res. 2024;84(9_Supplement):RF02-3-RF-3. https://doi.org/10.1158/1538-7445.Sabcs23-rf02-03.

Article  Google Scholar 

Iwai T, Sugimoto M, Wakita D, Yorozu K, Kurasawa M, Yamamoto K. Topoisomerase I inhibitor, irinotecan, depletes regulatory T cells and up-regulates MHC class I and PD-L1 expression, resulting in a supra-additive antitumor effect when combined with anti-PD-L1 antibodies. Oncotarget. 2018;9(59):31411–21. https://doi.org/10.18632/oncotarget.25830.

Article  PubMed  PubMed Central  Google Scholar 

Aea Garrido-Castro. SACI-IO HR+: A randomized phase II trial of sacituzumab govitecan with or without pembrolizumab in patients with metastatic hormone receptor-positive/HER2-negative breast cancer. J Clin Oncol. 2024;42(17_Supplement):LBA1004.