Research progress on targeted therapy of breast cancer with low expression of HER2

doi:10.3760/cma.j.cn371439-20221230-00046

Abstract

Abstract:

Breast cancer has become the malignant tumor with the highest incidence rate among women， of which human epidermal growth factor receptor 2 （HER2） positive breast cancer accounts for about 15%-20%. With the development of anti HER2 targeted drugs， the survival and prognosis of HER2 positive breast cancer has significantly benefited. About 45%-55% of breast cancer patients have low HER2 expression， and these patients usually do not receive anti HER2 treatment. However， there is a significant difference between the biological behavior and prognosis of breast cancer with low HER2 expression and breast cancer with zero HER2 expression. It is helpful to differentiate and adopt corresponding treatment strategies to improve the prognosis of patients. At present， there have been many advances in targeted therapy of breast cancer with low HER2 expression， which provides a useful reference for precision treatment of breast cancer with low HER2 expression.

Key words: Receptor, erbB-2, Breast neoplasms, Molecular targeted therapy

Zhu Jun, Huang Meijin, Li Yuan, Liu Zegang, Xun Xin, Chen Hong. Research progress on targeted therapy of breast cancer with low expression of HER2[J]. Journal of International Oncology, 2023, 50(4): 236-240.

References 32

[1]	Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249. DOI: 10.3322/caac.21660. doi: 10.3322/caac.21660
[2]	郑荣寿, 孙可欣, 张思维, 等. 2015年中国恶性肿瘤流行情况分析[J]. 中华肿瘤杂志, 2019, 41(1): 19-28. DOI: 10.3760/cma.j.issn.0253-3766.2019.01.008. doi: 10.3760/cma.j.issn.0253-3766.2019.01.008
[3]	Gradishar WJ, Moran MS, Abraham J, et al. Breast Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology[J]. J Natl Compr Canc Netw, 2022, 20(6): 691-722. DOI: 10.6004/jnccn.2022.0030. doi: 10.6004/jnccn.2022.0030
[4]	Tarantino P, Hamilton E, Tolaney SM, et al. HER2-low breast cancer: pathological and clinical landscape[J]. J Clin Oncol, 2020, 38(17): 1951-1962. DOI: 10.1200/JCO.19.02488. doi: 10.1200/JCO.19.02488 pmid: 32330069
[5]	Zhang H, Peng Y. Current biological, pathological and clinical landscape of HER2-low breast cancer[J]. Cancers (Basel), 2022, 15(1): 126. DOI: 10.3390/cancers15010126. doi: 10.3390/cancers15010126
[6]	Perez J, Garrigós L, Gion M, et al. Trastuzumab deruxtecan in HER2-positive metastatic breast cancer and beyond[J]. Expert Opin Biol Ther, 2021, 21(7): 811-824. DOI: 10.1080/14712598.2021.1890710. doi: 10.1080/14712598.2021.1890710 pmid: 33759669
[7]	中国临床肿瘤学会指南工作委员会. 中国临床肿瘤学会(CSCO)乳腺癌诊疗指南 2022[M]. 北京: 人民卫生出版社, 2022.
[8]	Tarantino P, Gandini S, Nicolò E, et al. Evolution of low HER2 expression between early and advanced-stage breast cancer[J]. Eur J Cancer, 2022, 163: 35-43. DOI: 10.1016/j.ejca.2021.12.022. doi: 10.1016/j.ejca.2021.12.022 pmid: 35032815
[9]	Zhang H, Katerji H, Turner BM, et al. HER2-low breast cancers[J]. Am J Clin Pathol, 2022, 157(3): 328-336. DOI: 10.1093/ajcp/aqab117. doi: 10.1093/ajcp/aqab117
[10]	Ferrando-Díez A, Felip E, Pous A, et al. Targeted therapeutic options and future perspectives for HER2-positive breast cancer[J]. Cancers (Basel), 2022, 14(14): 3305. DOI: 10.3390/cancers14143305. doi: 10.3390/cancers14143305
[11]	Schettini F, Chic N, Brasó-Maristany F, et al. Clinical, pathological, and PAM50 gene expression features of HER2-low breast cancer[J]. NPJ Breast Cancer, 2021, 7(1): 1. DOI: 10.1038/s41523-020-00208-2. doi: 10.1038/s41523-020-00208-2 pmid: 33397968
[12]	Mohamed M, Mohd Nafi SN, Jaafar H, et al. A retrospective hospital-based study of HMGCR expression in HER2 IHC 2+ and 3+ breast cancer[J]. Asian Pac J Cancer Prev, 2021, 22(7): 2043-2047. DOI: 10.31557/APJCP.2021.22.7.2043. doi: 10.31557/APJCP.2021.22.7.2043
[13]	Denkert C, Seither F, Schneeweiss A, et al. Clinical and molecular characteristics of HER2-low-positive breast cancer: pooled analysis of individual patient data from four prospective, neoadjuvant clinical trials[J]. Lancet Oncol, 2021, 22(8): 1151-1161. DOI: 10.1016/S1470-2045(21)00301-6. doi: 10.1016/S1470-2045(21)00301-6 pmid: 34252375
[14]	Zhang G, Ren C, Li C, et al. Distinct clinical and somatic mutational features of breast tumors with high-, low-, or non-expressing human epidermal growth factor receptor 2 status[J]. BMC Med, 2022, 20(1): 142. DOI: 10.1186/s12916-022-02346-9. doi: 10.1186/s12916-022-02346-9 pmid: 35484593
[15]	Chumsri S, Li Z, Serie DJ, et al. Incidence of late relapses in patients with HER2-positive breast cancer receiving adjuvant trastuzumab: combined analysis of NCCTG N9831 (alliance) and NRG oncology/NSABP B-31[J]. J Clin Oncol, 2019, 37(35): 3425-3435. DOI: 10.1200/JCO.19.00443. doi: 10.1200/JCO.19.00443 pmid: 31622131
[16]	Chumsri S, Serie DJ, Li Z, et al. Effects of age and immune landscape on outcome in HER2-positive breast cancer in the NCCTG N9831 (alliance) and NSABP B-31 (NRG) trials[J]. Clin Cancer Res, 2019, 25(14): 4422-4430. DOI: 10.1158/1078-0432.CCR-18-2206. doi: 10.1158/1078-0432.CCR-18-2206 pmid: 30808774
[17]	Fehrenbacher L, Cecchini RS, Geyer CE Jr, et al. NSABP B-47/NRG oncology phase Ⅲ randomized trial comparing adjuvant chemotherapy with or without trastuzumab in high-risk invasive breast cancer negative for HER2 by FISH and with IHC 1+ or 2[J]. J Clin Oncol, 2020, 38(5): 444-453. DOI: 10.1200/JCO.19.01455. doi: 10.1200/JCO.19.01455 pmid: 31821109
[18]	Modi S. Trastuzumab deruxtecan in previously treated HER2-positive metastatic breast cancer: plain language summary of the DESTINY-Breast01 study[J]. Future Oncol, 2021, 17(26): 3415-3423. DOI: 10.2217/fon-2021-0427. doi: 10.2217/fon-2021-0427 pmid: 34263665
[19]	U.S. Food & Drug Administration. FDA news release: FDA approves new treatment option for patients with HER2-positive breast cancer who have progressed on available therapies[EB/OL]. (2019-12-20)[2022-12-22]. https://www.fda.gov/news-events/press-announ-cements/fda-approves-new-treatment-option-patients-her2-positive-breast-cancer-who-have-progressed-available.
[20]	Modi S, Jacot W, Yamashita T, et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer[J]. N Engl J Med, 2022, 387(1): 9-20. DOI: 10.1056/NEJMoa2203690. doi: 10.1056/NEJMoa2203690
[21]	T-DXd: new standard for HER2-low breast cancer[J]. Cancer Discov, 2022, 12(8): 1828. DOI: 10.1158/2159-8290.CD-NB2022-0043. doi: 10.1158/2159-8290.CD-NB2022-0043 pmid: 35666611
[22]	Schlam I, Tolaney SM, Tarantino P. How I treat HER2-low advanced breast cancer[J]. Breast, 2023, 67: 116-123. DOI: 10. 1016/j.breast.2023.01.005. doi: 10. 1016/j.breast.2023.01.005
[23]	Tarantino P, Curigliano G, Tolaney SM. Navigating the HER2-low paradigm in breast oncology: new standards, future horizons[J]. Cancer Discov, 2022, 12(9): 2026-2030. DOI: 10.1158/2159-8290.CD-22-0703. doi: 10.1158/2159-8290.CD-22-0703
[24]	U.S. Food & Drug Administration. FDA news release: FDA approves first targeted therapy for HER2-low breast cancer[EB/OL]. (2022-08-05)[2022-09-07]. https://www.fda.gov/news-events/press-announcements/fda-approves-first-targeted-therapy-her2-low-breast-cancer.
[25]	Li H, Zhang X, Xu Z, et al. Preclinical evaluation of MRG002, a novel HER2-targeting antibody-drug conjugate with potent antitumor activity against HER2-positive solid tumors[J]. Antib Ther, 2021, 4(3): 175-184. DOI: 10.1093/abt/tbab017. doi: 10.1093/abt/tbab017 pmid: 34532642
[26]	Jiang Z, Sun T, Wang X, et al. A multiple center, open-label, single-arm, phase Ⅱ clinical trial of MRG002, an HER2-targeted antibody-drug conjugate, in patients with HER2-low expressing advanced or metastatic breast cancer[J]. J Clin Oncol, 2022, 40(16_suppl): 1102. DOI: 10.1200/JCO.2022.40.16_suppl.1102. doi: 10.1200/JCO.2022.40.16_suppl.1102
[27]	Banerji U, Saura C, et al. Trastuzumab duocarmazine in locally advanced and metastatic solid tumours and HER2-expressing breast cancer: a phase 1 dose-escalation and dose-expansion study[J]. Lancet Oncol, 2019, 20(8): 1124-1135. DOI: 10.1016/S1470-2045(19)30328-6. doi: S1470-2045(19)30328-6 pmid: 31257177
[28]	Saura C, Thistlethwaite F, Banerji U, et al. A phase Ⅰ expansion cohorts study of SYD985 in heavily pretreated patients with HER2-positive or HER2-low metastatic breast cancer[J]. J Clin Oncol, 2018, 36(15_suppl): 1014. DOI: 10.1200/JCO.2018.36.15_suppl.1014. doi: 10.1200/JCO.2018.36.15_suppl.1014
[29]	Xu B, Wang J, Fang J, et al. Abstract PD4-06: early clinical development of RC48-ADC in patients with HER2 positive metastatic breast cancer[J]. Cancer Res, 2020, 80(4_Supplement): PD4-06. DOI: 10.1158/1538-7445.SABCS19-PD4-06. doi: 10.1158/1538-7445.SABCS19-PD4-06
[30]	Wang J, Liu Y, Zhang Q, et al. RC48-ADC, a HER2-targeting antibody-drug conjugate, in patients with HER2-positive and HER2-low expressing advanced or metastatic breast cancer: a pooled analysis of two studies[J]. J Clin Oncol, 2021, 39(15_suppl): 1022. DOI: 10.1200/JCO.2021.39.15_suppl.1022. doi: 10.1200/JCO.2021.39.15_suppl.1022
[31]	Bergstrom D, Bodyak N, Park P, et al. Abstract P4-14-28: XMT-1522 induces tumor regressions in preclinical models representing HER2 positive and HER2 low expressing breast cancer[J]. Cancer Res, 2016, 76 (4_Supplement): P4-14-28. DOI: 10.1158/1538-7445.SABCS15-P4-14-28. doi: 10.1158/1538-7445.SABCS15-P4-14-28
[32]	Hamilton EP, Barve MA, Bardia A, et al. Phase 1 dose escalation of XMT-1522, a novel HER2-targeting antibody-drug conjugate (ADC), in patients (pts) with HER2-expressing breast, lung and gastric tumors[J]. J Clin Oncol, 2018, 36(15_suppl): 2546. DOI: 10.1200/JCO.2018.36.15_suppl.2546. doi: 10.1200/JCO.2018.36.15_suppl.2546