免疫检查点抑制剂在早期乳腺癌新辅助治疗中的研究进展

doi:10.11904/j.issn.1002-3070.2023.04.011

摘要/Abstract

摘要： 乳腺癌是全球发病率最高的癌症,整体预后较好,但经过手术治疗、化疗、放疗、内分泌治疗和靶向治疗后仍有部分患者出现肿瘤进展。对于疾病进展患者,免疫治疗成为一种可供选择的治疗方式。免疫检查点抑制剂(Immune checkpoint inhibitors,ICIs)作为免疫治疗主要方法之一,在乳腺癌治疗中的应用不断拓展,为新辅助治疗提供了新的选择,而新辅助治疗在提高保乳率、评估治疗效果、指导个体化治疗等方面具有重要的临床意义。本文将综述当前ICIs在早期乳腺癌各个亚型新辅助治疗中的临床研究进展。

关键词: 乳腺癌, 免疫检查点抑制剂, 新辅助治疗, 免疫治疗

Abstract: Breast cancer is the most common tumor worldwide with a good overall prognosis. However, some patients still endure tumor progression after surgery, chemotherapy, radiotherapy, endocrine therapy and targeted therapy. For patients with progressive disease, immunotherapy has become an alternative treatment option. As one of the main immunotherapeutic approaches, the application of immune checkpoint inhibitors(ICIs)in breast cancer treatment continues to expand, providing new options for neoadjuvant treatment, and neoadjuvant treatment improves breast conservation rates. It has important clinical significance in evaluating therapeutic efficacy, and guiding individualized treatment. This article will review the current clinical research progress of ICIs in the neoadjuvant treatment of various subtypes of early breast cancer.

Key words: Breast cancer, Immune checkpoint inhibitors, Neoadjuvant therapy, Immunotherapy

中图分类号:

R737.9

李福程, 贾斯媛, 巴玉玲, 罗丹利, 肖敏. 免疫检查点抑制剂在早期乳腺癌新辅助治疗中的研究进展[J]. 实用肿瘤学杂志, 2023, 37(4): 367-371.

LI Fucheng, JIA Siyuan, BA Yuling, LUO Danli, XIAO Min. Research progress of immune checkpoint inhibitors in neoadjuvant therapy of early breast cancer[J]. Journal of Practical Oncology, 2023, 37(4): 367-371.

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链接本文: http://journal09.magtechjournal.com/Jwk3_syzlxzz/CN/10.11904/j.issn.1002-3070.2023.04.011

http://journal09.magtechjournal.com/Jwk3_syzlxzz/CN/Y2023/V37/I4/367

参考文献

1 Topalian SL,Drake CG,Pardoll DM.Targeting the PD-1/B7-H1(PD-L1)pathway to activate anti-tumor immunity[J].Curr Opin Immunol,2012,24(2):207-212.
2 Mittendorf EA,Burgers F,Haanen J,et al.Neoadjuvant immunotherapy:leveraging the immune system to treat early-stage disease[J].Am Soc Clin Oncol Educ Book,2022,42:1-15.
3 Wang SL,Li YX,Song YW,et al.Triple-negative or HER2-positive status predicts higher rates of locoregional recurrence in node-positive breast cancer patients after mastectomy[J].Int J Radiat Oncol Biol Phys,2011,80(4):1095-1101.
4 Spring LM,Bar Y,Isakoff SJ.The evolving role of neoadjuvant therapy for operable breast cancer[J].J Natl Compr Canc Netw,2022,20(6):723-734.
5 Topalian SL,Taube JM,Pardoll DM.Neoadjuvant checkpoint blockade for cancer immunotherapy[J].Science,2020,367(6477):182.
6 Liu J,Blake SJ,Yong MC,et al.Improved efficacy of neoadjuvant compared to adjuvant immunotherapy to eradicate metastatic disease[J].Cancer Discov,2016,6(12):1382-1399.
7 Dieci MV,Griguolo G,Miglietta F,et al.The immune system and hormone-receptor positive breast cancer:is it really a dead end[J].Cancer Treat Rev,2016,46:9-19.
8 Burugu S,Asleh-Aburaya K,Nielsen TO.Immune infiltrates in the breast cancer microenvironment:detection,characterization and clinical implication[J].Breast Cancer,2017,24(1):3-15.
9 Sabatier R,Finetti P,Mamessier E,et al.Prognostic and predictive value of PDL1 expression in breast cancer[J].Oncotarget,2015,6(7):5449-5464.
10 Dieci MV,Guarneri V,Tosi A,et al.Neoadjuvant chemotherapy and immunotherapy in luminal b-like breast cancer:results of the phase II GIADA trial[J].Clin Cancer Res,2022,28(2):308-317.
11 Harrington D,Parmigiani G.I-SPY 2-a glimpse of the future of phase 2 drug development?[J].N Engl J Med 2016,375(1):7-9.
12 Nanda R,Liu MC,Yau C,et al.Effect of pembrolizumab plus neoadjuvant chemotherapy on pathologic complete response in women with early-stage breast cancer:an analysis of the ongoing phase 2 adaptively randomized I-SPY2 trial[J].JAMA Oncol,2020,6(5):676-684.
13 Pusztai L,Yau C,Wolf DM,et al.Durvalumab with olaparib and paclitaxel for high-risk HER2-negative stage II/III breast cancer:results from the adaptively randomized I-SPY2 trial[J].Cancer Cell,2021,39(7):989-998.
14 Cardoso F,Bardia A,André F,et al.KEYNOTE-756:randomized,double-blind,phase 3 study of pembrolizumab vs placebo combined with neoadjuvant chemotherapy and adjuvant endocrine therapy for high-risk,early-stage estrogen receptor–positive,human epidermal growth factor receptor 2–negative(ER+/HER2-)breast cancer[J].J Clin Oncol,2019,37(15_suppl):601.
15 Loi S,McArthur HL,Harbeck N,et al.A phase III trial of nivolumab with neoadjuvant chemotherapy and adjuvant endocrine therapy in ER+/HER2-primary breast cancer:CheckMate 7FL[J].J Clin Oncol,2020,38(15_suppl):604.
16 Kyriazoglou A,Kaparelou M,Goumas G,et al.Immunotherapy in HER2-positive breast cancer:a systematic review[J].Breast Care(Basel),2022,17(1):63-70.
17 Chaganty BKR,Qiu S,Gest A,et al.Trastuzumab upregulates PD-L1 as a potential mechanism of trastuzumab resistance through engagement of immune effector cells and stimulation of IFNγ secretion[J].Cancer Lett,2018,430:47-56.
18 Huober J,Barrios CH,Niikura N,et al.Atezolizumab with neoadjuvant anti-human epidermal growth factor receptor 2 therapy and chemotherapy in human epidermal growth factor receptor 2-positive early breast cancer:primary results of the randomized phase III IMpassion050 Trial[J].J Clin Oncol,2022,40(25):2946-2956.
19 Howard FM,Villamar D,He G,et al.The emerging role of immune checkpoint inhibitors for the treatment of breast cancer[J].Expert Opin Investig Drugs,2021,31(6):531-548.
20 Cortes J,Cescon DW,Rugo HS,et al.Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer(KEYNOTE-355):a randomised,placebo-controlled,double-blind,phase 3 clinical trial[J].Lancet,2020,396(10265):1817-1828.
21 Emens LA,Adams S,Barrios CH,et al.First-line atezolizumab plus nab-paclitaxel for unresectable,locally advanced,or metastatic triple-negative breast cancer:IMpassion130 final overall survival analysis[J].Ann Oncol,2021,32(8):983-993.
22 Keenan TE,Tolaney SM.Role of immunotherapy in triple-negative breast cancer[J].J Natl Compr Canc Netw,2020,18(4):479-489.
23 Barroso-Sousa R,Forman J,Collier K,et al.Multidimensional molecular profiling of metastatic triple-negative breast cancer and immune checkpoint inhibitor benefit[J].JCO Precis Oncol,2022,6:e2100413.
24 Pusztai L,Karn T,Safonov A,et al.New strategies in breast cancer:immunotherapy[J].Clin Cancer Res,2016,22(9):2105-2110.
25 Schmid P,Salgado R,Park YH,et al.Pembrolizumab plus chemotherapy as neoadjuvant treatment of high-risk,early-stage triple-negative breast cancer:results from the phase 1b open-label,multicohort KEYNOTE-173 study[J].Ann Oncol,2020,31(5):569-581.
26 Loibl S,Schneeweiss A,Huober J,et al.Neoadjuvant durvalumab improves survival in early triple-negative breast cancer independent of pathological complete response[J].Ann Oncol,2022,33(11):1149-1158.
27 Schmid P,Cortes J,Dent R.Pembrolizumab in early triple-negative breast cancer.reply[J].N Engl J Med,2022,386(18):1771-1772.
28 Mittendorf EA,Zhang H,Barrios CH,et al.Neoadjuvant atezolizumab in combination with sequential nab-paclitaxel and anthracycline-based chemotherapy versus placebo and chemotherapy in patients with early-stage triple-negative breast cancer(IMpassion031):a randomised,double-blind,phase 3 trial[J].Lancet,2020,396(10257):1090-1100.
29 Schmid P,Cortes J,Dent R,et al.Event-free survival with pembrolizumab in early triple-negative breast cancer[J].N Engl J Med,2022,386(6):556-567.
30 Korde LA,Somerfield MR,Hershman DL.Use of immune checkpoint inhibitor pembrolizumab in the treatment of high-risk,early-stage triple-negative breast cancer:ASCO guideline rapid recommendation update[J].J Clin Oncol,2022,40(15):1696-1698.
31 Yam C,Mittendorf EA,Garber HR,et al.A phase II study of neoadjuvant atezolizumab and nab-paclitaxel in patients with anthracycline-resistant early-stage triple-negative breast cancer[J].Breast Cancer Res Treat,2023,199(3):457-469.
32 Gianni L,Huang CS,Egle D,et al.Pathologic complete response(pCR)to neoadjuvant treatment with or without atezolizumab in triple-negative,early high-risk and locally advanced breast cancer:NeoTRIP Michelangelo randomized study[J].Ann Oncol,2022,33(5):534-543.
33 Vaes RDW,Hendriks LEL,Vooijs M,et al.Biomarkers of radiotherapy-induced immunogenic cell death[J].Cells,2021,10(4):930.
34 Koukourakis IM,Tiniakos D,Kouloulias V,et al.The molecular basis of immuno-radiotherapy[J].Int J Radiat Biol,2023,99(5):715-736.
35 Grassberger C,Huber K,Jacob NK,et al.Three discipline collaborative radiation therapy(3DCRT)special debate:The single most important factor in determining the future of SBRT is immune response[J].J Appl Clin Med Phys,2019,20(10):6-12.
36 Koukourakis IM,Papadimitriou M,Desse D,et al.Anti-tumor immunity and preoperative radiovaccination:emerging new concepts in the treatment of breast cancer[J].Int J Mol Sci,2023,24(11):9310.
37 Tchou J,Clark A,Taunk N,et al.Major pathologic response after a single radiotherapy fraction + a single pembrolizumab dose given preoperatively in patients with cT1N0 triple negative breast cancer(TNBC)-preliminary results of a phase 1b/2 study(NCT04454528)[J].J Immunother Cancer,2022,10(Suppl 2):675.

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