Overview of systemic therapy for advanced triple-negative breast cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

ZHANG Lu , ZHANG Xiaosan , WANG Fang ,  LIU Zhenzhen

Department of Breast Disease, Henan Breast Cancer Centre, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou 450000, P. R. China;

Corresponding author：

LIU Zhenzhen, Email: zlyyliuzhenzhen0800@zzu.edu.cn

Keywords：

triple-negative breast cancer; immune checkpoint inhibitors; antibody-drug conjugates; poly ADP-ribose polymerase inhibitors; systemic therapy

DOI：

10.7507/1007-9424.202508070

Video：

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Objective To sort out the key evidence-based data and recent advances in the systemic treatment of advanced triple-negative breast carcinoma (TNBC), to summarize the therapeutic strategies so as to provide guidance for clinical practice. Methods The key evidence and research progress on immune checkpoint inhibitors, antibody–drug conjugates (ADCs), poly ADP-ribose polymerase (PARP) inhibitors, anti-angiogenic agents, and novel microtubule inhibitors were summarized. Results The treatment landscape for advanced TNBC has shifted from chemotherapy-centric approaches to biomarker-driven, stratified precision therapy. Based on programmed cell death ligand 1 (PD-L1) expression levels, immune therapy combined with chemotherapy is prioritized. For cases with germline breast cancer gene 1/2 (gBRCA1/2) mutations, PARP inhibitors are recommended. ADCs are suggested for second-line treatment, while novel microtubule inhibitors, either alone or in combination with anti-angiogenic agents, are preferred for later-line therapy to extend patient survival. Conclusion Dynamic monitoring of molecular biomarkers such as PD-L1 and gBRCA, combined with sequential or combined "targeted–immunotherapy–ADC" regimens in a "chemotherapy-free" approach, has shown promise in improving overall survival in advanced TNBC.

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2. Punie K, Kurian AW, Ntalla I, et al. Unmet need for previously untreated metastatic triple-negative breast cancer: a real-world study of patients diagnosed from 2011 to 2022 in the United States. Oncologist, 2025, 30(3): oyaf034. doi: 10.1093/oncolo/oyaf034.
3. Schmid P, Adams S, Rugo HS, et al. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med, 2018, 379(22): 2108-2121.
4. 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. Lancet, 2020, 396(10265): 1817-1828.
5. Im SA, Cortes J, Cescon DW, et al. Results from the randomized KEYNOTE-355 study of pembrolizumab plus chemotherapy for Asian patients with advanced TNBC. NPJ Breast Cancer, 2024, 10(1): 79.
6. Cortes J, Rugo HS, Cescon DW, et al. Pembrolizumab plus chemotherapy in advanced triple-negative breast cancer. N Engl J Med, 2022, 387(3): 217-226.
7. Adams S, Schmid P, Rugo HS, et al. Pembrolizumab monotherapy for previously treated metastatic triple-negative breast cancer: cohort A of the phase Ⅱ KEYNOTE-086 study. Ann Oncol, 2019, 30(3): 397-404.
8. Jiang Z, Ouyang Q, Sun T, et al. Toripalimab plus nab-paclitaxel in metastatic or recurrent triple-negative breast cancer: a randomized phase 3 trial. Nat Med, 2024, 30(1): 249-256.
9. 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. Ann Oncol, 2021, 32(8): 983-993.
10. Miles D, Gligorov J, André F, et al. Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase Ⅲ trial of first-line paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer. Ann Oncol, 2021, 32(8): 994-1004.
11. Dent R, André F, Gonçalves A, et al. IMpassion132 double-blind randomised phase Ⅲ trial of chemotherapy with or without atezolizumab for early relapsing unresectable locally advanced or metastatic triple-negative breast cancer. Ann Oncol, 2024, 35(7): 630-642.
12. Franzoi MA, de Azambuja E. Atezolizumab in metastatic triple-negative breast cancer: IMpassion130 and 131 trials—how to explain different results?. ESMO Open, 2020, 5(6): e001112. doi: 10.1136/esmoopen-2020-001112.
13. Zhang Y, Chen H, Mo H, et al. Single-cell analyses reveal key immune cell subsets associated with response to PD-L1 blockade in triple-negative breast cancer. Cancer Cell, 2021, 39(12): 1578-1593.
14. Ran R, Chen X, Yang J, et al. Immunotherapy in breast cancer: current landscape and emerging trends. Exp Hematol Oncol, 2025, 14(1): 77. doi: 10.1186/s40164-025-00667-y.
15. Bardia A, Mayer IA, Vahdat LT, et al. Sacituzumab govitecan-hziy in refractory metastatic triple-negative breast cancer. N Engl J Med, 2019, 380(8): 741-751.
16. Bardia A, Hurvitz SA, Tolaney SM, et al. Sacituzumab govitecan in metastatic triple-negative breast cancer. N Engl J Med, 2021, 384(16): 1529-1541.
17. Rugo HS, Tolaney SM, Loirat D, et al. Safety analyses from the phase 3 ASCENT trial of sacituzumab govitecan in metastatic triple-negative breast cancer. NPJ Breast Cancer, 2022, 8(1): 98. doi: 10.1038/s41523-022-00467-1.
18. Bardia A, Rugo HS, Tolaney SM, et al. Final results from the randomized phase Ⅲ ASCENT clinical trial in metastatic triple-negative breast cancer and association of outcomes by human epidermal growth factor receptor 2 and trophoblast cell surface antigen 2 expression. J Clin Oncol, 2024, 42(15): 1738-1744.
19. Xu B, Ma F, Wang T, et al. A phase Ⅱb, single arm, multicenter trial of sacituzumab govitecan in Chinese patients with metastatic triple-negative breast cancer who received at least two prior treatments. Int J Cancer, 2023, 152(10): 2134-2144.
20. Tolaney SM, de Azambuja E, Kalinsky K, et al. Sacituzumab govitecan (SG) + pembrolizumab (pembro) vs chemotherapy (chemo) + pembro in previously untreated PD-L1–positive advanced triple-negative breast cancer (TNBC): primary results from the randomized phase 3 ASCENT-04/KEYNOTE-D19 study. J Clin Oncol, 2025, 43(17_suppl): LBA109-LBA109. doi: 10.1200/JCO.2025.43.17_suppl.LBA109.
21. Ouyang Q, Rodon J, Liang Y, et al. Results of a phase 1/2 study of sacituzumab tirumotecan in patients with unresectable locally advanced or metastatic solid tumors refractory to standard therapies. J Hematol Oncol, 2025, 18(1): 61. doi: 10.1186/s13045-025-01705-2.
22. Yin Y, Fan Y, Ouyang Q, et al. Sacituzumab tirumotecan in previously treated metastatic triple-negative breast cancer: a randomized phase 3 trial. Nat Med, 2025, 31(6): 1969-1975.
23. Yin Y, Ouyang Q, Yan M, et al. Sacituzumab tirumotecan (sac-TMT) as first-line treatment for unresectable locally advanced/metastatic triple-negative breast cancer (a/mTNBC): initial results from the phase Ⅱ OptiTROP-Breast05 study. J Clin Oncol, 2025, 43(16_suppl): 1019-1019.
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