Real-world outcome of neoadjuvant therapy with or without pembrolizumab for triple-negative breast cancer

Authors

DOI:

https://doi.org/10.2340/1651-226X.2026.44896

Keywords:

Triple-negative breast cancer, neoadjuvant therapy, pembrolizumab, Neoadjuvant chemotherapy, real-word evidence, efficacy, adverse effects

Abstract

Background and purpose: Neoadjuvant therapy (NAT) has become standard therapy for early triple-negative breast cancer (TNBC). The aim of this study was to report real-world outcome of TNBC treated with NAT with or without pembrolizumab and to identify predictive factors for achieving pathologic complete response (pCR) in the pembrolizumab cohort.

Patient/material and methods: The data of 75 consecutive TNBC patients treated with neoadjuvant chemotherapy and pembrolizumab at the Helsinki University Hospital Comprehensive Cancer Center were retrospectively collected. Treatment outcome and predictive factors for pCR were analyzed. Additionally, the outcome of nonmatched 102 consecutive TNBC patients treated without pembrolizumab during the preceding years is reported.

Results: Forty-two patients (56.0%) achieved pCR to pembrolizumab-based NAT, while 47 patients (46.1%) without pembrolizumab had pCR. Lymph node metastasis (p = 0.011) and multifocality (p < 0.001) were inversely associated with pCR in the pembrolizumab cohort. Thirty-four patients (45.3%) had immune-related adverse events (irAEs), and 11 patients (14.7%) had grade 1–2 myocarditis in the pembrolizumab cohort. Due to adverse events (AEs), pembrolizumab was discontinued in 22 patients (29.3%) in the neoadjuvant setting, not started postoperatively in 21 patients (28%) and discontinued postoperatively in eight patients (10.7%). The number of preoperative pembrolizumab cycles was not associated with pCR.

Interpretation: Despite higher incidence of myocarditis and interruption of the systemic therapy due to irAEs, higher pCR rates were seen with pembrolizumab. Even though the number of  preoperative pembrolizumab cycles was not associated with pCR monitoring and limiting AEs is important.

Downloads

Download data is not yet available.

References

Waks AG, Winer EP. Breast cancer treatment. JAMA. 2019;321(3):288–300.

https://doi.org/10.1001/jama.2018.19323 DOI: https://doi.org/10.1001/jama.2018.19323

Zhou HL, Chen DD. Prognosis of patients with triple-negative breast cancer: a population-based study from SEER database. Clin Breast Cancer. 2023;23(3):e85–94.

https://doi.org/10.1016/j.clbc.2023.01.002 DOI: https://doi.org/10.1016/j.clbc.2023.01.002

Loibl S, André F, Bachelot T, Barrios CH, Bergh J, Bursyein HJ, et al. Early breast cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2024;35(2):159–82.

https://doi.org/10.1016/j.annonc.2023.11.016 DOI: https://doi.org/10.1016/j.annonc.2023.11.016

Bonadio RC, Tarantino P, Testa L, Punie K, Pernas S, Barrios C, et al. Management of patients with early-stage triple-negative breast cancer following pembrolizumab-based neoadjuvant therapy: what are the evidences? Cancer Treat Rev. 2022;110:102459.

https://doi.org/10.1016/j.ctrv.2022.102459 DOI: https://doi.org/10.1016/j.ctrv.2022.102459

Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014;384(9938):164–72.

https://doi.org/10.1016/S0140-6736(13)62422-8 DOI: https://doi.org/10.1016/S0140-6736(13)62422-8

Spring LM, Fell G, Arfe A, Sharma C, Greenup R, Reynolds KL, et al. Pathologic complete response after neoadjuvant chemotherapy and impact on breast cancer recurrence and survival: a comprehensive meta-analysis. Clin Cancer Res. 2020;26(12):2838–48.

https://doi.org/10.1158/1078-0432.CCR-19-3492 DOI: https://doi.org/10.1158/1078-0432.CCR-19-3492

Al-Hilli Z, Choong G, Keeney MG, Visscher DW, Ingle JN, Goetz MP, et al. Metaplastic breast cancer has a poor response to neoadjuvant systemic therapy. Breast Cancer Res Treat. 2019;176(3):709–16.

https://doi.org/10.1007/s10549-019-05264-2 DOI: https://doi.org/10.1007/s10549-019-05264-2

El-Naggar AI, Karakatsanis A, Valachisa A. Real-world survival outcomes of neoadjuvant versus adjuvant chemotherapy in operable triple-negative breast cancer: a propensity score matched registry-based study. Acta Oncol. 2025;64:1334–41.

https://doi.org/10.2340/1651-226X.2025.43990 DOI: https://doi.org/10.2340/1651-226X.2025.43990

Zhang M, Song J, Yang H, Jin F, Zheng A. Efficacy and safety of PD-1/PD-L1 inhibitors in triple-negative breast cancer: a systematic review and meta-analysis. Acta Oncol. 2022;61(9):1105–15.

https://doi.org/10.1080/0284186X.2022.2106795 DOI: https://doi.org/10.1080/0284186X.2022.2106795

Schmid P, Cortes J, Pusztai L, McArthur H, Kümmel S, Bergh J, et al. Pembrolizumab for early triple-negative breast cancer. N Engl J Med. 2020;382:810–21.

https://doi.org/10.1056/NEJMoa1910549 DOI: https://doi.org/10.1056/NEJMoa1910549

Schmid P, Cortes J, Dent R, Pusztai L, McArthur H, Kümmel S, et al. Event-free survival with pembrolizumab in early triple-negative breast cancer. N Engl J Med. 2022;386:556–67.

https://doi.org/10.1056/NEJMoa2112651 DOI: https://doi.org/10.1056/NEJMoa2112651

Schmid P, Cortes J, Dent R, McArthur H, Pusztai L, Kümmel S, et al. Overall survival with pembrolizumab in early-stage triple-negative breast cancer. N Engl J Med. 2024;391:1981–91.

https://doi.org/10.1056/NEJMoa2409932 DOI: https://doi.org/10.1056/NEJMoa2409932

Woodfin AA, Yam C, Teshome M, Kuerer HM, Hunt KK, Meric-Bernstam F, et al. Axillary nodal metastases conversion and perioperative complications with neoadjuvant pembrolizumab therapy in triple-negative breast cancer. Ann Surg Oncol. 2024;31:974–80.

https://doi.org/10.1245/s10434-023-14541-w DOI: https://doi.org/10.1245/s10434-023-14541-w

Dent R, Cortés J, Pusztai L, McArthur H, Kümmel S, Bergh J, et al. Neoadjuvant pembrolizumab plus chemotherapy/adjuvant pembrolizumab for early-stage triple-negative breast cancer: quality-of-life results from the randomized KEYNOTE-522 study. J Natl Cancer Inst. 2024;116:1654–63.

https://doi.org/10.1093/jnci/djae129 DOI: https://doi.org/10.1093/jnci/djae129

von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP; STROBE Initiative. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE)statement: guidelines for reporting observational studies. J Clin Epidemiol. 2008 Apr;61(4):344-9. PMID: 18313558 Available from: https://www.strobe-statement.org/checklists/ DOI: https://doi.org/10.1016/j.jclinepi.2007.11.008

The Oncovalue Consortium funded by the European Union, Brussels. Available from: https://oncovalue.org/

U.S. Department of Health and Human Services, National Cancer Institute, Maryland. Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. 2017.

Lyon AR, López-Fernández T, Couch LS, Asteggiano R, Aznar MC, Bergler-Klein J, et al. 2022 ESC guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart J. 2022;43:4229–61.

https://doi.org/10.1093/eurheartj/ehac244 DOI: https://doi.org/10.1093/eurheartj/ehac244

Mezzanotte-Sharpe J, Hsu CY, Choi D, Sheffield H, Zelinskas S, Proskuriakova E, et al. Adverse events in patients treated with neoadjuvant chemo/immunotherapy for triple negative breast cancer: results from seven academic medical centers. Breast Cancer Res Treat. 2025;213(1):71–80.

https://doi.org/10.1007/s10549-025-07758-8 DOI: https://doi.org/10.1007/s10549-025-07758-8

Connors C, Valente SA, ElSherif A, Escobar P, Chichura A, Kopicky L, et al. Real-world outcomes with the KEYNOTE-522 regimen in early-stage triple-negative breast cancer. Ann Surg Oncol. 2025;32(2):912–21.

https://doi.org/10.1245/s10434-024-16390-7 DOI: https://doi.org/10.1245/s10434-024-16390-7

Marhold M, Udovica S, Halstead A, Hirdler M, Ferner M, Wimmer K, et al. Emergence of immune-related adverse events correlates with pathological complete response in patients receiving pembrolizumab for early triple-negative breast cancer. Onco Immunol. 2023;12(1):2275846.

https://doi.org/10.1080/2162402X.2023.2275846 DOI: https://doi.org/10.1080/2162402X.2023.2275846

Aoyama Y, Ozaki Y, Kizawa R, Masuda J, Kawai S, Kurata M, et al. Efficacy and feasibility of neoadjuvant pembrolizumab plus chemotherapy for early-stage triple-negative and estrogen receptor low, HER2-negative breast cancer: a Japanese single-institution real-world study. Breast Cancer. 2025;32:329–36.

https://doi.org/10.1007/s12282-024-01657-4 DOI: https://doi.org/10.1007/s12282-024-01657-4

Rached L, Peyre-Pradat F, Spotti M, Baldini C, Laparra A, Lambotte O, et al. Real-world safety and effectiveness of neoadjuvant chemotherapy combination with pembrolizumab in triple-negative breast cancer. ESMO Real World Data Digit Oncol. 2024;5:100061.

https://doi.org/10.1016/j.esmorw.2024.100061 DOI: https://doi.org/10.1016/j.esmorw.2024.100061

LeVee A, Wong M, Flores S, Ruel N, McArthur H, Waisman J, et al. Impact of neoadjuvant pembrolizumab adherence on pathologic complete response in triple-negative breast cancer: a real-world analysis. Oncologist. 2024;29(7):566–74.

https://doi.org/10.1093/oncolo/oyae064 DOI: https://doi.org/10.1093/oncolo/oyae064

Krishnan J, Patel A, Roy AM, Alharbi M, Kapoor A, Yao S, et al. Detrimental impact of chemotherapy dose reduction or discontinuation in early-stage triple-negative breast cancer treated with pembrolizumab and neoadjuvant chemotherapy: a multi-center experience. Clin Breast Cancer. 2024;24(8):e701–11.e2.

https://doi.org/10.1016/j.clbc.2024.08.005 DOI: https://doi.org/10.1016/j.clbc.2024.08.005

Iwamoto T, Booser D, Valero V, Murray JL, Koenig K, Esteva FJ, et al. Estrogen receptor (ER) mRNA and ER-related gene expression in breast cancers that are 1% to 10% ER-positive by immunohistochemistry. J Clin Oncol. 2012;30(7):729–34.

https://doi.org/10.1200/JCO.2011.36.2574 DOI: https://doi.org/10.1200/JCO.2011.36.2574

Ohara AM, Naoi Y, Shimazu K, Kagara N, Shimoda M, Tanei T, et al. PAM50 for prediction of response to neoadjuvant chemotherapy for ER-positive breast cancer. Breast Cancer Res Treat. 2019;173(3):533–43.

https://doi.org/10.1007/s10549-018-5020-7 DOI: https://doi.org/10.1007/s10549-018-5020-7

Landmann A, Farrugia DJ, Zhu L, Diego EJ, Johnson RR, Soran A, et al. Low estrogen receptor (ER)-positive breast cancer and neoadjuvant systemic chemotherapy: is response similar to typical ER-positive or ER-negative disease? Am J Clin Pathol. 2018;150(1):34–42.

https://doi.org/10.1093/ajcp/aqy028 DOI: https://doi.org/10.1093/ajcp/aqy028

Dieci MV, Griguolo G, Bottosso M, Tsvetkova V, Giorgi CA, Vernaci G, et al. Impact of estrogen receptor levels on outcome in non-metastatic triple negative breast cancer patients treated with neoadjuvant/adjuvant chemotherapy. NPJ Breast Cancer. 2021;7(1):101.

https://doi.org/10.1038/s41523-021-00308-7 DOI: https://doi.org/10.1038/s41523-021-00308-7

Wood SJ, Gao Y, Lee JH, Chen J, Wang Q, Meisel JL, et al. High tumor infiltrating lymphocytes are significantly associated with pathological complete response in triple negative breast cancer treated with neoadjuvant KEYNOTE-522 chemoimmunotherapy. Breast Cancer Res Treat. 2024;205(1):193–9.

https://doi.org/10.1007/s10549-023-07233-2 DOI: https://doi.org/10.1007/s10549-023-07233-2

Arnaud E, Vaflard P, Escalup L, Ramtohul T, Meziani D, Thibault L, et al. Treatment toxicities and pathological response through the evolution of neoadjuvant regimens in early triple-negative breast cancer. ESMO Real World Data Digit Oncol. 2025;9:100157.

https://doi.org/10.1016/j.esmorw.2025.100157 DOI: https://doi.org/10.1016/j.esmorw.2025.100157

Gaudet C, Varnier R, Dalle S, Bouali A, Courand PY, Reverdy T. Cardiotoxicity in combination of pembrolizumab and anthracyclines in neoadjuvant treatment for early triplenegative breast cancer: a monocentric retrospective cohort study. Ann Oncol. 2025;36:S1501.

https://doi.org/10.1016/j.annonc.2025.08.3444 DOI: https://doi.org/10.1016/j.annonc.2025.08.3444

Yam C, Abuhadra N, Sun R, Adrada BE, Ding QQ, White JB, et al. Molecular characterization and prospective evaluation of pathologic response and outcomes with neoadjuvant therapy in metaplastic triple-negative breast cancer. Clin Cancer Res. 2022;28:2878–89.

https://doi.org/10.1158/1078-0432.CCR-21-3100 DOI: https://doi.org/10.1158/1078-0432.CCR-21-3100

Published

2026-02-19

How to Cite

Maunu, M., Lähteenmaa, J., Karihtala, P., Tuohinen, S., Laaksolilja, J., Ståhls, A., … Mattson, J. (2026). Real-world outcome of neoadjuvant therapy with or without pembrolizumab for triple-negative breast cancer. Acta Oncologica, 65, 131–140. https://doi.org/10.2340/1651-226X.2026.44896