Metastatic triple-negative breast cancer – current treatment strategies in the Nordics: a modified Delphi study

Authors

  • Antonis Valachis Department of Oncology, Faculty of Medicine and Health, Örebro University, Örebro, Örebro, Sweden
  • Peeter Karihtala Department of Oncology, Helsinki University Hospital Comprehensive Cancer Centre and University of Helsinki, Helsinki, Finland
  • Jürgen Geisler Department of Oncology, Division of Medicine, Akershus University Hospital (AHUS), Lørenskog, Norway & Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Campus AHUS, Norway
  • Malgorzata K. Tuxen Department of Oncology, Herlev and Gentofte University Hospital, Herlev, Denmark

DOI:

https://doi.org/10.2340/1651-226X.2025.42733

Keywords:

mTNBC, Delphi method, Treatment guidelines, Nordics

Abstract

Background and purpose: This study aimed to assess current treatment strategies for metastatic triple-negative breast cancer (mTNBC) and the perceptions of clinical experts in Sweden, Denmark, Norway, Finland, and Iceland, comparing them to international guidelines to provide insights into how these therapies are implemented and adapted to national Nordic guidelines.

Methods: A three-round modified Delphi method was followed with consensus defined as 70% agreement. A steering committee selected 20 experienced oncologists as panellists and developed the questionnaires. Questions included items related to treatment preferences in different treatment lines with different clinical scenarios in mTNBC patients.

Results: In the first round, eight out of 33 questions on clinical treatment reached consensus with 14 out of 27 in the second round reaching consensus. In round three, eight out of eight questions reached consensus. The preferred treatment for mTNBC patients with PD-L1 positive was checkpoint inhibitors (CPI) in combination with chemotherapy. For patients with germline BRCA mutation and PD-L1 negative disease, PARP-inhibitors were preferred as 1L and sacituzumab govitecan (SG) in both 2L and later lines. Disagreement was observed for chemotherapy in later lines where evidence is sparse or lacking.

Interpretation: The high level of consensus for new treatment strategies, such as CPI and PARP-inhibitors in 1L and SG in 2L or later lines, in comparison with the limited consensus for older treatments, such as chemotherapy, may reflect the growing academic evidence for different treatment strategies. Understanding the treatment patterns across different countries contributes to gaining consensus on the upcoming therapeutic advances.

Downloads

Download data is not yet available.

References

Ferlay J, Ervik M, Lam F, Laversanne M, Colombet M, Mery L, et al. Global cancer observatory: cancer today (version 1.1). Lyon, France: International Agency for Research on Cancer; 2024. [Accessed: February 20, 2025] Available from: https://gco.iarc.who.int/today

Dafni U, Tsourti Z, Alatsathianos I. Breast cancer statistics in the European Union: incidence and survival across European countries. Breast Care (Basel). 2019;14(6):344–53.

https://doi.org/10.1159/000503219 DOI: https://doi.org/10.1159/000503219

Yao H, He G, Yan S, Chen C, Song L, Rosol TJ, et al. Triple-negative breast cancer: is there a treatment on the horizon? Oncotarget. 2017;8(1):1913–24.

https://doi.org/10.18632/oncotarget.12284 DOI: https://doi.org/10.18632/oncotarget.12284

Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y, et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest. 2011;121(7):2750–67.

https://doi.org/10.1172/JCI45014 DOI: https://doi.org/10.1172/JCI45014

Cortes J, Rugo HS, Cescon DW, Im SA, Yusof MM, Gallardo C, et al. Pembrolizumab plus chemotherapy in advanced triple-negative breast cancer. N Engl J Med. 2022;387(3):217–26.

https://doi.org/10.1056/NEJMoa2202809 DOI: https://doi.org/10.1056/NEJMoa2202809

Bardia A, Hurvitz SA, Tolaney SM, Loirat D, Punie K, Oliveira M, et al. Sacituzumab Govitecan in metastatic triple-negative breast cancer. N Engl J Med. 2021;384(16):1529–41.

https://doi.org/10.1056/NEJMoa2028485 DOI: https://doi.org/10.1056/NEJMoa2028485

Bardia A, Rugo HS, Tolaney SM, Loirat D, Punie K, Oliveira M, 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):1738–44.

https://doi.org/10.1200/JCO.23.01409 DOI: https://doi.org/10.1200/JCO.23.01409

Modi S, Jacot W, Yamashita T, Sohn J, Vidal M, Tokunaga E, et al. Trastuzumab Deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med. 2022;387(1):9–20. DOI: https://doi.org/10.1056/NEJMoa2203690

Barchiesi G, Roberto M, Verrico M, Vici P, Tomao S, Tomao F. Emerging role of PARP-inhibitors in metastatic triple negative breast cancer. Current scenario and future perspectives. Front Oncol. 2021;11:769280.

https://doi.org/10.3389/fonc.2021.769280 DOI: https://doi.org/10.3389/fonc.2021.769280

Robson M, Im SA, Senkus E, Xu B, Domchek SM, Masuda N, et al. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N Engl J Med. 2017;377(6):523–33.

https://doi.org/10.1056/NEJMoa1706450 DOI: https://doi.org/10.1056/NEJMoa1706450

Litton JK, Rugo HS, Ettl J, Hurvitz SA, Goncalves A, Lee KH, et al. Talazoparib in patients with advanced breast cancer and a germline BRCA mutation. N Engl J Med. 2018;379(8):753–63.

https://doi.org/10.1056/NEJMoa1802905 DOI: https://doi.org/10.1056/NEJMoa1802905

European Society for Medical Oncology (ESMO). ESMO metastatic breast cancer living guideline – triple-negative breast cancer. 2023. [Accessed: February 20, 2025] Available from: https://www.esmo.org/living-guidelines/esmo-metastatic-breast-cancer-living-guideline/triple-negative-breast-cancer

Nasa P, Jain R, Juneja D. Delphi methodology in healthcare research: how to decide its appropriateness. World J Methodol. 2021;11(4):116–29.

https://doi.org/10.5662/wjm.v11.i4.116 DOI: https://doi.org/10.5662/wjm.v11.i4.116

Geisler J, Karihtala P, Tuxen M, Valachis A, Delphi Panellist G, Holm B. Current treatment landscape of HR+/HER2- advanced breast cancer in the Nordics: a modified Delphi study. Acta Oncol. 2023;62(12):1680–8.

https://doi.org/10.1080/0284186X.2023.2254475 DOI: https://doi.org/10.1080/0284186X.2023.2254475

SurveyMonkey®. SurveyMonkey®. 1999–2024. [Accessed: February 20, 2025] Available from: https://uk.surveymonkey.com/

PigeonLab Pte. Ltd. Pigeonhole Live™ [online software]. 2024. [Accessed: February 20, 2025] Available from: https://pigeonholelive.com/

European Medicines Agency (EMA). EMA recommendations on DPD testing prior to treatment with fluorouracil, capecitabine, tegafur and flucytosine. 2020, EMA, Amstedam, the Netherlands.

Schmid P, Adams S, Rugo HS, Schneeweiss A, Barrios CH, Iwata H, et al. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med. 2018;379(22):2108–21.

https://doi.org/10.1056/NEJMoa1809615 DOI: https://doi.org/10.1056/NEJMoa1809615

Miles D, Gligorov J, Andre F, Cameron D, Schneeweiss A, Barrios C, 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. DOI: https://doi.org/10.1016/j.annonc.2021.05.801

Hu XC, Zhang J, Xu BH, Cai L, Ragaz J, Wang ZH, et al. Cisplatin plus gemcitabine versus paclitaxel plus gemcitabine as first-line therapy for metastatic triple-negative breast cancer (CBCSG006): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2015;16(4):436–46.

https://doi.org/10.1016/S1470-2045(15)70064-1 DOI: https://doi.org/10.1016/S1470-2045(15)70064-1

Yardley DA, Coleman R, Conte P, Cortes J, Brufsky A, Shtivelband M, et al. nab-Paclitaxel plus carboplatin or gemcitabine versus gemcitabine plus carboplatin as first-line treatment of patients with triple-negative metastatic breast cancer: results from the tnAcity trial. Ann Oncol. 2018;29(8):1763–70. DOI: https://doi.org/10.1093/annonc/mdy201

Pivot X, Marmé F, Koenigsberg R, Guo M, Berrak E, Wolfer A. Pooled analyses of eribulin in metastatic breast cancer patients with at least one prior chemotherapy. Ann Oncol. 2016;27(8):1525–31.

https://doi.org/10.1093/annonc/mdw203 DOI: https://doi.org/10.1093/annonc/mdw203

Paakkola NM, Karakatsanis A, Mauri D, Foukakis T, Valachis A. The prognostic and predictive impact of low estrogen receptor expression in early breast cancer: a systematic review and meta-analysis. ESMO Open. 2021;6(6):100289.

https://doi.org/10.1016/j.esmoop.2021.100289 DOI: https://doi.org/10.1016/j.esmoop.2021.100289

Acs B, Hartman J, Sönmez D, Lindman H, Johansson ALV, Fredriksson I. Real-world overall survival and characteristics of patients with ER-zero and ER-low HER2-negative breast cancer treated as triple-negative breast cancer: a Swedish population-based cohort study. Lancet Reg Health Eur. 2024;40:100886.

https://doi.org/10.1016/j.lanepe.2024.100886 DOI: https://doi.org/10.1016/j.lanepe.2024.100886

Donohoe HM, Needham RD. Moving best practice forward: Delphi characteristics, advantages, potential problems, and solutions. Int J Tour Res. 2008;11(5):415–37.

https://doi.org/10.1002/jtr.709 DOI: https://doi.org/10.1002/jtr.709

Emens LA, Molinero L, Loi S, Rugo HS, Schneeweiss A, Diéras V, et al. Atezolizumab and nab-Paclitaxel in advanced triple-negative breast cancer: biomarker evaluation of the IMpassion130 study. J Natl Cancer Inst. 2021;113(8):1005–16.

https://doi.org/10.1093/jnci/djab004 DOI: https://doi.org/10.1093/jnci/djab004

Bae SJ, Seoung Ho B, Kook Y, Kim JH, Minji L, et al. Efficacy of neoadjuvant pembrolizuamb in early triple-negative breast cancer according to germline BRCA-1/2 mutation. Ann Oncol. 2024;35:S1406.

https://doi.org/10.1016/j.annonc.2024.10.023 DOI: https://doi.org/10.1016/j.annonc.2024.10.023

Shahbandi A, Chiu FY, Ungerleider NA, Kvadas R, Mheidly Z, Sun MJS, et al. Breast cancer cells survive chemotherapy by activating targetable immune-modulatory programs characterized by PD-L1 or CD80. Nat Cancer. 2022;3(12):1513–33.

https://doi.org/10.1038/s43018-022-00466-y DOI: https://doi.org/10.1038/s43018-022-00466-y

Additional Files

Published

2025-03-05

How to Cite

Valachis, A., Karihtala, P., Geisler, J., & Tuxen, M. K. (2025). Metastatic triple-negative breast cancer – current treatment strategies in the Nordics: a modified Delphi study. Acta Oncologica, 64, 349–357. https://doi.org/10.2340/1651-226X.2025.42733