Prospect of Neoadjuvant/adjuvant Immunotherapy in Early-stage Triple-negative Breast Cancer

Overview

Journal Transl Breast Cancer Res

Publisher AME Publishing Company

Date 2024 May 16

PMID 38751481

Authors

Xiaopeng Hao

Xianqi Gao

Shanshan Yin

Zefei Jiang

Affiliations

Soon will be listed here.

Abstract

China is bearing the growing burden of breast cancer globally, accounting for 18% of all new cases. Triple-negative breast cancer (TNBC) is aggressive, prone to early recurrence and metastasis, with a poor prognosis. Improving the prognosis at the early-stage of TNBC remains a challenge, due to the limited efficacy of traditional neoadjuvant/adjuvant chemotherapy. Early studies revealed that early-stage TNBC is more immunogenic. Several current clinical trials revealed that the combination with immunotherapy in the form of immune checkpoint inhibitors (ICIs) expands the treatment options for early-stage TNBC by improving the pathologic complete response (pCR), as well as long-term survival benefits. Correspondingly, Chinese Society of Clinical Oncology (CSCO) updated the breast cancer guidelines to include several recommendations regarding neoadjuvant/adjuvant immunotherapy. However, relevant immunotherapy data in Chinese patients with early-stage TNBC remain scarce. The cTRIO clinical trial (ChiCTR2100041675) is a multicenter phase II trial initiated by investigators to evaluate tislelizumab combined with nab-paclitaxel and carboplatin in neoadjuvant/ adjuvant therapy for Chinese patients with TNBC. In this review, we discuss the latest advances in clinical studies of neoadjuvant/adjuvant immunotherapy for early-stage TNBC, as well as potential challenges and strategies to improve the clinical outcomes. We introduce the study design of the cTRIO trial, which aims to make the clinical benefits more robust for early-stage TNBC patients in China.

Citing Articles

Hot issues in triple-negative breast cancer.

Hao X, Jiang Z Cancer Biol Med. 2024; 20(12).

PMID: 38318879 PMC: 10845930. DOI: 10.20892/j.issn.2095-3941.2023.0294.

Unveiling the Immune Microenvironment's Role in Breast Cancer: A Glimpse into Promising Frontiers.

Kotsifaki A, Alevizopoulos N, Dimopoulou V, Armakolas A Int J Mol Sci. 2023; 24(20).

PMID: 37895012 PMC: 10607694. DOI: 10.3390/ijms242015332.

References

Sistigu A, Yamazaki T, Vacchelli E, Chaba K, Enot D, Adam J . Cancer cell-autonomous contribution of type I interferon signaling to the efficacy of chemotherapy. Nat Med. 2014; 20(11):1301-9. DOI: 10.1038/nm.3708. View

Nanda R, Liu M, Yau C, Shatsky R, Pusztai L, Wallace A . 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. JAMA Oncol. 2020; 6(5):676-684. PMC: 7058271. DOI: 10.1001/jamaoncol.2019.6650. View

Cortes J, Cescon D, Rugo H, Nowecki Z, Im S, Yusof M . 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. DOI: 10.1016/S0140-6736(20)32531-9. View

Jiang Z, Li J, Chen J, Liu Y, Wang K, Nie J . Chinese Society of Clinical Oncology (CSCO) Breast Cancer Guidelines 2022. Transl Breast Cancer Res. 2024; 3:13. PMC: 11093004. DOI: 10.21037/tbcr-22-21. View

Denkert C, Loibl S, Noske A, Roller M, Muller B, Komor M . Tumor-associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer. J Clin Oncol. 2009; 28(1):105-13. DOI: 10.1200/JCO.2009.23.7370. View

Duan J, Cui L, Zhao X, Bai H, Cai S, Wang G . Use of Immunotherapy With Programmed Cell Death 1 vs Programmed Cell Death Ligand 1 Inhibitors in Patients With Cancer: A Systematic Review and Meta-analysis. JAMA Oncol. 2019; 6(3):375-384. PMC: 6990765. DOI: 10.1001/jamaoncol.2019.5367. View

Barroso-Sousa R, Tolaney S . Pembrolizumab in the preoperative setting of triple-negative breast cancer: safety and efficacy. Expert Rev Anticancer Ther. 2020; 20(11):923-930. DOI: 10.1080/14737140.2020.1823224. View

Gluz O, Nitz U, Liedtke C, Christgen M, Grischke E, Forstbauer H . Comparison of Neoadjuvant Nab-Paclitaxel+Carboplatin vs Nab-Paclitaxel+Gemcitabine in Triple-Negative Breast Cancer: Randomized WSG-ADAPT-TN Trial Results. J Natl Cancer Inst. 2017; 110(6):628-637. DOI: 10.1093/jnci/djx258. View

Dahan R, Sega E, Engelhardt J, Selby M, Korman A, Ravetch J . FcγRs Modulate the Anti-tumor Activity of Antibodies Targeting the PD-1/PD-L1 Axis. Cancer Cell. 2015; 28(3):285-95. DOI: 10.1016/j.ccell.2015.08.004. View

10.

Chen D, Mellman I . Elements of cancer immunity and the cancer-immune set point. Nature. 2017; 541(7637):321-330. DOI: 10.1038/nature21349. View

11.

Schmid P, Cortes J, Pusztai L, McArthur H, Kummel S, Bergh J . Pembrolizumab for Early Triple-Negative Breast Cancer. N Engl J Med. 2020; 382(9):810-821. DOI: 10.1056/NEJMoa1910549. View

12.

Emens L, Cruz C, Eder J, Braiteh F, Chung C, Tolaney S . Long-term Clinical Outcomes and Biomarker Analyses of Atezolizumab Therapy for Patients With Metastatic Triple-Negative Breast Cancer: A Phase 1 Study. JAMA Oncol. 2018; 5(1):74-82. PMC: 6439773. DOI: 10.1001/jamaoncol.2018.4224. View

13.

Schmid P, Cortes J, Dent R, Pusztai L, McArthur H, Kummel S . Event-free Survival with Pembrolizumab in Early Triple-Negative Breast Cancer. N Engl J Med. 2022; 386(6):556-567. DOI: 10.1056/NEJMoa2112651. View

14.

Miyashita M, Ishida T . Prospect of immunotherapy in neoadjuvant/adjuvant treatment for early breast cancer. Chin Clin Oncol. 2020; 9(3):28. DOI: 10.21037/cco.2020.04.01. View

15.

Zhang P, Yin Y, Mo H, Zhang B, Wang X, Li Q . Better pathologic complete response and relapse-free survival after carboplatin plus paclitaxel compared with epirubicin plus paclitaxel as neoadjuvant chemotherapy for locally advanced triple-negative breast cancer: a randomized phase 2 trial. Oncotarget. 2016; 7(37):60647-60656. PMC: 5312408. DOI: 10.18632/oncotarget.10607. View

16.

Untch M, Jackisch C, Schneeweiss A, Conrad B, Aktas B, Denkert C . Nab-paclitaxel versus solvent-based paclitaxel in neoadjuvant chemotherapy for early breast cancer (GeparSepto-GBG 69): a randomised, phase 3 trial. Lancet Oncol. 2016; 17(3):345-356. DOI: 10.1016/S1470-2045(15)00542-2. View

17.

Cloughesy T, Mochizuki A, Orpilla J, Hugo W, Lee A, Davidson T . Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma. Nat Med. 2019; 25(3):477-486. PMC: 6408961. DOI: 10.1038/s41591-018-0337-7. View

18.

Kwapisz D . Pembrolizumab and atezolizumab in triple-negative breast cancer. Cancer Immunol Immunother. 2020; 70(3):607-617. PMC: 10992894. DOI: 10.1007/s00262-020-02736-z. View

19.

Mittendorf E, Zhang H, Barrios C, Saji S, Jung K, Hegg R . 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.... Lancet. 2020; 396(10257):1090-1100. DOI: 10.1016/S0140-6736(20)31953-X. View

20.

Mittendorf E, Philips A, Meric-Bernstam F, Qiao N, Wu Y, Harrington S . PD-L1 expression in triple-negative breast cancer. Cancer Immunol Res. 2014; 2(4):361-70. PMC: 4000553. DOI: 10.1158/2326-6066.CIR-13-0127. View