Adjuvant and Neoadjuvant Immunotherapy for Breast Cancer

Sabin GÖKTAŞ AYDINa , Ahmet BİLİCİb
aİstanbul Kanuni Sultan Süleyman Training and Research Hospital, Clinic of Medical Oncology, İstanbul, Türkiye
bİstanbul Medipol University Faculty of Medicine, Department of Medical Oncology, İstanbul, Türkiye

Göktaş Aydın S, Bilici A. Adjuvant and neoadjuvant immunotherapy for breast cancer. In: Şendur MAN, ed. Current Immunotherapy Landscape for Solid Tumors. 1st ed. Ankara: Türkiye Klinikleri; 2024. p.65-71.

Adjuvant and Neoadjuvant Immunotherapy for Breast Cancer

Meme Kanserinde Adjuvan ve Neoadjuvan İmmünoterapi

Sabin GÖKTAŞ AYDINa , Ahmet BİLİCİb
aİstanbul Kanuni Sultan Süleyman Training and Research Hospital, Clinic of Medical Oncology, İstanbul, Türkiye
bİstanbul Medipol University Faculty of Medicine, Department of Medical Oncology, İstanbul, Türkiye

Göktaş Aydın S, Bilici A. Adjuvant and neoadjuvant immunotherapy for breast cancer. In: Şendur MAN, ed. Current Immunotherapy Landscape for Solid Tumors. 1st ed. Ankara: Türkiye Klinikleri; 2024. p.65-71.

Makale Dili: EN

Ücretsiz Erişim

ABSTRACT
Breast cancer, the most common malignancy in women, necessitates a comprehensive approach involving surgery, medical oncology, and radiation oncology. The AJCC staging incorporates biologic features alongside TNM classification to determine the cancer stage. Early and locally advanced breast cancer requires systemic treatment to reduce the risk of recurrence. Achieving pathological complete response (pCR) through neoadjuvant therapy is a strong prognostic factor. Immunotherapy, targeting PD-1/PD-L1 has shown promise, particularly in triple-negative breast cancer (TNBC). KEYNOTE-522 study demonstrated improved pCR and event-free survival (EFS) rates with pembrolizumab in neoadjuvant setting. Atezolizumab, when combined with nab-paclitaxel, increased pCR rates in IMPASSION031 trial. While neoadjuvant immunotherapy presents potential advantages, the safety profile and long-term efficacy are still evolving. Future studies should focus on optimal treatment duration and sequencing, especially in adjuvant settings.

Keywords: Breast cancer; immunotherapy; adjuvant treatment; neoadjuvant treatment

Referanslar

  1. [Link]
  2. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Statistics, 2021. CA Cancer J Clin. 2021;71(1):7-33. Erratum in: CA Cancer J Clin. 2021;71(4):359. [Crossref]  [PubMed]
  3. Kesson EM, Allardice GM, George WD, Burns HJ, Morrison DS. Effects of multidisciplinary team working on breast cancer survival: retrospective, comparative, interventional cohort study of 13 722 women. BMJ. 2012;344:e2718. [Crossref]  [PubMed]  [PMC]
  4. AJCC (American Joint Committee on Cancer) Cancer Staging Manual; 8th ed. 3rd printing. In: Amin MB, Edge SB, Greene FL, et al. eds. Chicago: Springer; 2018.
  5. Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials. Lancet Oncol. 2018;19(1):27-39. [Crossref]  [PubMed]
  6. 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. Erratum in: Lancet. 2019;393(10175):986. [Crossref]  [PubMed]
  7. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology. Breast cancer. (Version 4.2023) [Link]
  8. Steenbruggen TG, van Werkhoven E, van Ramshorst MS, Dezentjé VO, Kok M, Linn SC, et al. Adjuvant chemotherapy in small node-negative triple-negative breast cancer. Eur J Cancer. 2020;135:66-74. [Crossref]  [PubMed]
  9. Geyer CE Jr, Garber JE, Gelber RD, Yothers G, Taboada M, Ross L, et al.; OlympiA Clinical Trial Steering Committee and Investigators. Overall survival in the OlympiA phase III trial of adjuvant olaparib in patients with germline pathogenic variants in BRCA1/2 and high-risk, early breast cancer. Ann Oncol. 2022;33(12):1250-68. [Crossref]  [PubMed]  [PMC]
  10. Masuda N, Lee SJ, Ohtani S, Im YH, Lee ES, Yokota I, et al. Adjuvant Capecitabine for Breast Cancer after Preoperative Chemotherapy. N Engl J Med. 2017;376(22):2147-59. [Crossref]  [PubMed]
  11. Liedtke C, Mazouni C, Hess KR, André F, Tordai A, Mejia JA, et al. Response to Neoadjuvant Therapy and Long-Term Survival in Patients With Triple-Negative Breast Cancer. J Clin Oncol. 2023;41(10):1809-15. [Crossref]  [PubMed]
  12. Jin J, Zhang W, Ji W, Yang F, Guan X. Predictive biomarkers for triple negative breast cancer treated with platinum-based chemotherapy. Cancer Biol Ther. 2017;18(6):369-78. [Crossref]  [PubMed]  [PMC]
  13. Pandy JGP, Balolong-Garcia JC, Cruz-Ordinario MVB, Que FVF. Triple negative breast cancer and platinum-based systemic treatment: a meta-analysis and systematic review. BMC Cancer. 2019;19(1):1065. [Crossref]  [PubMed]  [PMC]
  14. Abramson VG, Mayer IA. Molecular Heterogeneity of Triple Negative Breast Cancer. Curr Breast Cancer Rep. 2014;6(3):154-8. [Crossref]  [PubMed]  [PMC]
  15. Wei SC, Duffy CR, Allison JP. Fundamental Mechanisms of Immune Checkpoint Blockade Therapy. Cancer Discov. 2018;8(9):1069-86. [Crossref]  [PubMed]
  16. Lotfinejad P, Kazemi T, Mokhtarzadeh A, Shanehbandi D, Jadidi Niaragh F, Safaei S, et al. PD-1/PD-L1 axis importance and tumor microenvironment immune cells. Life Sci. 2020;259:118297. [Crossref]  [PubMed]
  17. He Q, Peng Y, Sun J, Liu J. Platinum-Based Chemotherapy and Immunotherapy in Early Triple-Negative Breast Cancer: A Meta-Analysis and Indirect Treatment Comparison. Front Oncol. 2021;11:693542. [Crossref]  [PubMed]  [PMC]
  18. United States Department of Health and Human Services. Guidance for industry-pathological complete response in neoadjuvant treatment of high-risk early-stage breast cancer: use as an endpoint to support accelerated approval; 2014. Available from: [Link]
  19. Broglio KR, Quintana M, Foster M, Olinger M, McGlothlin A, Berry SM, et al. Association of Pathologic Complete Response to Neoadjuvant Therapy in HER2-Positive Breast Cancer With Long-Term Outcomes: A Meta-Analysis. JAMA Oncol. 2016;2(6):751-60. [Crossref]  [PubMed]
  20. Huang M, O'Shaughnessy J, Zhao J, Haiderali A, Cortés J, Ramsey SD, et al. Association of Pathologic Complete Response with Long-Term Survival Outcomes in Triple-Negative Breast Cancer: A Meta-Analysis. Cancer Res. 2020;80(24):5427-34. [Crossref]  [PubMed]
  21. Gianni L, Huang CS, Egle D, Bermejo B, Zamagni C, Thill M, 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. Ann Oncol. 2022;33(5):534-43. [Crossref]  [PubMed]
  22. Mittendorf EA, Zhang H, Barrios CH, Saji S, Jung KH, Hegg R, 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. Lancet. 2020;396(10257):1090-100. [Crossref]  [PubMed]
  23. Nanda R, Liu MC, Yau C, Shatsky R, Pusztai L, Wallace A, 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. JAMA Oncol. 2020;6(5):676-84. [Crossref]  [PubMed]  [PMC]
  24. Schmid P, Cortes J, Pusztai L, McArthur H, Kümmel S, Bergh J, et al.; KEYNOTE-522 Investigators. Pembrolizumab for Early Triple-Negative Breast Cancer. N Engl J Med. 2020;382(9):810-21. [Crossref]  [PubMed]
  25. Loibl S, Untch M, Burchardi N, Huober J, Sinn BV, Blohmer JU, et al. A randomised phase II study investigating durvalumab in addition to an anthracycline taxane-based neoadjuvant therapy in early triple-negative breast cancer: clinical results and biomarker analysis of GeparNuevo study. Ann Oncol. 2019;30(8):1279-88. Erratum in: Ann Oncol. 2022;33(7):743-44. [Crossref]  [PubMed]
  26. FDA approves pembrolizumab for high-risk early-stage triple-negative breast cancer. [cited: Aug 26, 2021]. Avaiable from: [Link]
  27. Schmid P, Park YH, Muñoz-Couselo E, Kim SB, Sohn J, Im SA, et al. Pembrolizumab (pembro) + chemotherapy (chemo) as neoadjuvant treatment for triple negative breast cancer (TNBC): preliminary results from KEYNOTE-173. J Clin Oncol. 2017;35:Suppl:556 (abstract). [Crossref]
  28. Schmid P, Cortes J, Dent R, Pusztai L, McArthur H, Kümmel S, et al.; KEYNOTE-522 Investigators. Event-free Survival with Pembrolizumab in Early Triple-Negative Breast Cancer. N Engl J Med. 2022;386(6):556-67. [Crossref]  [PubMed]
  29. Loibl S, Schneeweiss A, Huober J, Braun M, Rey J, Blohmer JU, et al.; GBG and AGO-B. Neoadjuvant durvalumab improves survival in early triple-negative breast cancer independent of pathological complete response. Ann Oncol. 2022;33(11):1149-58. [Crossref]  [PubMed]
  30. Dirix LY, Takacs I, Jerusalem G, Nikolinakos P, Arkenau HT, Forero-Torres A, et al. Avelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN Solid Tumor study. Breast Cancer Res Treat. 2018;167(3):671-86. [Crossref]  [PubMed]  [PMC]
  31. La Rocca E, Dispinzieri M, Lozza L, Mariani G, Di Cosimo S, Gennaro M, et al. Radiotherapy with the anti-programmed cell death ligand-1 immune checkpoint blocker avelumab: acute toxicities in triple-negative breast cancer. Med Oncol. 2018;36(1):4. [Crossref]  [PubMed]
  32. Tarantino P, Gandini S, Trapani D, Criscitiello C, Curigliano G. Immunotherapy addition to neoadjuvant chemotherapy for early triple negative breast cancer: A systematic review and meta-analysis of randomized clinical trials. Crit Rev Oncol Hematol. 2021;159:103223. [Crossref]  [PubMed]
  33. 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. [Crossref]  [PubMed]
  34. Tutt ANJ, Garber JE, Kaufman B, Viale G, Fumagalli D, Rastogi P, et al.; OlympiA Clinical Trial Steering Committee and Investigators. Adjuvant Olaparib for Patients with BRCA1- or BRCA2-Mutated Breast Cancer. N Engl J Med. 2021;384(25):2394-405. [Crossref]  [PubMed]  [PMC]
  35. Shah AN, Flaum L, Helenowski I, Santa-Maria CA, Jain S, Rademaker A, et al. Phase II study of pembrolizumab and capecitabine for triple negative and hormone receptor-positive, HER2-negative endocrine-refractory metastatic breast cancer. J Immunother Cancer. 2020;8(1):e000173. [Crossref]  [PubMed]  [PMC]
  36. Yu EY, Massard C, Retz M, Tafreshi A, Carles, Galceran JC, et al. Pembrolizumab (pembro) plus olaparib in docetaxel-pretreated patients (pts) with metastatic castrate-resistant prostate cancer (mCRPC): Cohort A of the phase 1b/2 KEYNOTE-365 study. Journal of Clinical Oncology. 2019;37(Issue 7 Suppl):5027. [Crossref]
  37. [Link]