Online first
Review paper
Published online: 2023-12-05

open access

Page views 254
Article views/downloads 134
Get Citation

Connect on Social Media

Connect on Social Media

Systemic treatment in triple-negative breast cancer patients — standard and novel approaches

Sylwia Dębska-Szmich1, Piotr Potemski1


In recent years, after a long standstill in pharmacotherapy of triple-negative breast cancer (TNBC), several new targeted agents have been registered for treatment of patients with this neoplasm (pembrolizumab, olaparib, talazoparib, sacituzumab govitecan, and trastuzumab deruxtecan). 

The standard treatment for patients with early TNBC and operable primary tumors up to 2 cm and negative lymph nodes is primary surgery followed by adjuvant chemotherapy and possible radiotherapy. Patients with higher local and regional stages are candidates for primary chemotherapy followed by radical surgery and adjuvant treatment. Adjuvant olaparib prolongs invasive disease-free survival and overall survival of patients with germline BRCA1/2 mutation. Adding pembrolizumab to perioperative systemic treatment increases the pathological complete response rate (pCR) and prolongs event-free survival. However, there are no data on effectiveness and safety of applying combined immunotherapy with adjuvant capecitabine for patients without pCR after preoperative treatment or with adjuvant olaparib for germline BRCA1/2 mutation carriers. 

Chemotherapy is the standard treatment for advanced TNBC. Palliative treatment with PARP inhibitors (olaparib, talazoparib) in patients with germline BRCA1/2 mutation prolongs progression-free survival and increases the overall response rate compared with chemotherapy. 

In PD-L1-positive patients, adding pembrolizumab to first-line chemotherapy increases the response rate and prolongs survival. The same endpoints are better for TNBC patients treated with sacituzumab govitecan compared with chemotherapy. Trastuzumab deruxtecan is indicated for the treatment of patients with low human epidermal growth factor receptor 2 (HER2) expression and ismore efficient than chemotherapy. In Poland, pembrolizumab, talazoparib, and sacituzumab govitecan are reimbursed from public funds. 

Article available in PDF format

View PDF Download PDF file


  1. Wolff AC, Hammond ME, Allison KH, et al. HER2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update Summary. J Oncol Pract. 2018; 14(7): 437–441.
  2. Burstein MD, Tsimelzon A, Poage GM, et al. Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer. Clin Cancer Res. 2015; 21(7): 1688–1698.
  3. Cardoso F, Kyriakides S, Ohno S, et al. ESMO Guidelines Committee. Electronic address: Early breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†. Ann Oncol. 2019; 30(8): 1194–1220; Erratum in: Ann Oncol. 2021; 32(2): 284.
  5. Blum JL, Flynn PJ, Yothers G, et al. Anthracyclines in Early Breast Cancer: The ABC Trials-USOR 06-090, NSABP B-46-I/USOR 07132, and NSABP B-49 (NRG Oncology). J Clin Oncol. 2017; 35(23): 2647–2655.
  6. 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.
  7. Yau C, Osdoit M, van der Noordaa M, et al. I-SPY 2 Trial Consortium. Residual cancer burden after neoadjuvant chemotherapy and long-term survival outcomes in breast cancer: a multicentre pooled analysis of 5161 patients. Lancet Oncol. 2022; 23(1): 149–160.
  8. Masuda N, Lee SJ, Ohtani S, et al. Adjuvant Capecitabine for Breast Cancer after Preoperative Chemotherapy. N Engl J Med. 2017; 376(22): 2147–2159.
  9. Pathak M, Dwivedi S, Deo S, et al. Effectiveness of taxanes over anthracyclines in neoadjuvant setting: A systematic-review and meta-analysis. World Journal of Meta-Analysis. 2019; 7(4): 170–183.
  10. Zaheed M, Wilcken N, Willson ML, et al. Sequencing of anthracyclines and taxanes in neoadjuvant and adjuvant therapy for early breast cancer. Cochrane Database Syst Rev. 2019; 2(2): CD012873.
  11. Ding Y, Ding K, Yang H, et al. Does dose-dense neoadjuvant chemotherapy have clinically significant prognostic value in breast cancer?: A meta-analysis of 3,724 patients. PLoS One. 2020; 15(5): e0234058.
  12. Poggio F, Bruzzone M, Ceppi M, et al. Platinum-based neoadjuvant chemotherapy in triple-negative breast cancer: a systematic review and meta-analysis. Ann Oncol. 2018; 29(7): 1497–1508.
  13. Poggio F, Tagliamento M, Ceppi M, et al. Adding a platinum agent to neoadjuvant chemotherapy for triple-negative breast cancer: the end of the debate. Ann Oncol. 2022; 33(3): 347–349.
  14. Geyer CE, Sikov WM, Huober J, et al. Long-term efficacy and safety of addition of carboplatin with or without veliparib to standard neoadjuvant chemotherapy in triple-negative breast cancer: 4-year follow-up data from BrighTNess, a randomized phase III trial. Ann Oncol. 2022; 33(4): 384–394.
  15. Loibl S, Weber KE, Timms KM, et al. Survival analysis of carboplatin added to an anthracycline/taxane-based neoadjuvant chemotherapy and HRD score as predictor of response-final results from GeparSixto. Ann Oncol. 2018; 29(12): 2341–2347.
  16. Gupta S, Nair N, Hawaldar R, et al. Abstract GS5-01: Addition of platinum to sequential taxane-anthracycline neoadjuvant chemotherapy in patients with triple-negative breast cancer: A phase III randomized controlled trial. Cancer Research. 2023; 83(5_Supplement): GS5-01-GS5–01.
  17. Mayer IA, Zhao F, Arteaga CL, et al. Randomized Phase III Postoperative Trial of Platinum-Based Chemotherapy Versus Capecitabine in Patients With Residual Triple-Negative Breast Cancer Following Neoadjuvant Chemotherapy: ECOG-ACRIN EA1131. J Clin Oncol. 2021; 39(23): 2539–2551.
  18. Schmid P, Cortes J, Pusztai L, et al. KEYNOTE-522 Investigators. Pembrolizumab for Early Triple-Negative Breast Cancer. N Engl J Med. 2020; 382(9): 810–821.
  19. Schmid P, Cortes J, Dent R, et al. KEYNOTE-522 Investigators. Event-free Survival with Pembrolizumab in Early Triple-Negative Breast Cancer. N Engl J Med. 2022; 386(6): 556–567.
  20. Mittendorf EA, Zhang H, Barrios CH, 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): 1090–1100.
  21. Barrios C, Harbeck N, Zhang HA, et al. LBA1 Final analysis of the placebo-controlled randomised phase III IMpassion031 trial evaluating neoadjuvant atezolizumab (atezo) plus chemotherapy (CT) followed by open-label adjuvant atezo in patients (pts) with early-stage triple-negative breast cancer (eTNBC). ESMO Open. 2023; 8(1): 101571.
  22. Loibl S, Schneeweiss A, Huober J, 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): 1149–1158.
  23. Geyer C, Loibl S, Rastogi P, et al. NSABP B-59/GBG 96-GeparDouze: A randomized double-blind phase III clinical trial of neoadjuvant chemotherapy (NAC) with atezolizumab or placebo in Patients (pts) with triple negative breast cancer (TNBC) followed by adjuvant atezolizumab or placebo. Journal of Clinical Oncology. 2018; 36(15_suppl): TPS603–TPS603.
  24. Geyer CE, Garber JE, Gelber RD, et al. OlympiA Clinical Trial Steering Committee and Investigators, OlympiA Clinical Trial Steering Committee and Investigators. Adjuvant Olaparib for Patients with - or -Mutated Breast Cancer. N Engl J Med. 2021; 384(25): 2394–2405.
  25. Geyer CE, Garber JE, Gelber RD, 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): 1250–1268.
  26. Loibl S, O'Shaughnessy J, Untch M, et al. Addition of the PARP inhibitor veliparib plus carboplatin or carboplatin alone to standard neoadjuvant chemotherapy in triple-negative breast cancer (BrighTNess): a randomised, phase 3 trial. Lancet Oncol. 2018; 19(4): 497–509.
  27. Litton J, Beck J, Jones J, et al. Neoadjuvant talazoparib in patients with germline BRCA1/2 (gBRCA1/2) mutation-positive, early HER2-negative breast cancer (BC): Results of a phase 2 study. Journal of Clinical Oncology. 2021; 39(15_suppl): 505–505.
  28. Tutt A, Tovey H, Cheang MC, et al. Carboplatin in BRCA1/2-mutated and triple-negative breast cancer BRCAness subgroups: the TNT Trial. Nat Med. 2018; 24(5): 628–637.
  29. Tarantino P, Hamilton E, Tolaney SM, et al. HER2-Low Breast Cancer: Pathological and Clinical Landscape. J Clin Oncol. 2020; 38(17): 1951–1962.
  30. Litton JK, Rugo HS, Ettl J, et al. Talazoparib in Patients with Advanced Breast Cancer and a Germline BRCA Mutation. N Engl J Med. 2018; 379(8): 753–763.
  31. Litton JK, Hurvitz SA, Mina LA, et al. Talazoparib versus chemotherapy in patients with germline BRCA1/2-mutated HER2-negative advanced breast cancer: final overall survival results from the EMBRACA trial. Ann Oncol. 2020; 31(11): 1526–1535.
  32. Robson M, Im SA, Senkus E, et al. Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation. N Engl J Med. 2017; 377(6): 523–533.
  33. Robson ME, Tung N, Conte P, et al. OlympiAD final overall survival and tolerability results: Olaparib versus chemotherapy treatment of physician's choice in patients with a germline BRCA mutation and HER2-negative metastatic breast cancer. Ann Oncol. 2019; 30(4): 558–566.
  34. Diéras V, Han HS, Kaufman B, et al. Veliparib with carboplatin and paclitaxel in BRCA-mutated advanced breast cancer (BROCADE3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2020; 21(10): 1269–1282.
  35. Bardia A, Hurvitz SA, Tolaney SM, et al. ASCENT Clinical Trial Investigators. Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer. N Engl J Med. 2021; 384(16): 1529–1541.
  36. Diéras V, Weaver R, Tolaney S, et al. Abstract PD13-07: Subgroup analysis of patients with brain metastases from the phase 3 ASCENT study of sacituzumab govitecan versus chemotherapy in metastatic triple-negative breast cancer. Cancer Research. 2021; 81(4_Supplement): PD13-07-PD13–07.
  37. Wahby S, Fashoyin-Aje L, Osgood CL, et al. FDA Approval Summary: Accelerated Approval of Sacituzumab Govitecan-hziy for Third-line Treatment of Metastatic Triple-negative Breast Cancer. Clin Cancer Res. 2021; 27(7): 1850–1854.
  38. Bardia A, Tolaney SM, Punie K, et al. Biomarker analyses in the phase III ASCENT study of sacituzumab govitecan versus chemotherapy in patients with metastatic triple-negative breast cancer. Ann Oncol. 2021; 32(9): 1148–1156.
  39. Tolaney S, Bardia A, Marmé F, et al. Final overall survival (OS) analysis from the phase 3 TROPiCS-02 study of sacituzumab govitecan (SG) in patients (pts) with hormone receptor–positive/HER2-negative (HR+/HER2–) metastatic breast cancer (mBC). Journal of Clinical Oncology. 2023; 41(16_suppl): 1003–1003.
  40. Cortes J, Cescon DW, Rugo HS, et al. KEYNOTE-355 Investigators. 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.
  41. Winer EP, Lipatov O, Im SA, et al. KEYNOTE-119 investigators. Pembrolizumab versus investigator-choice chemotherapy for metastatic triple-negative breast cancer (KEYNOTE-119): a randomised, open-label, phase 3 trial. Lancet Oncol. 2021; 22(4): 499–511.
  42. Schmid P, Adams S, Rugo HS, et al. IMpassion130 Trial Investigators. Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. N Engl J Med. 2018; 379(22): 2108–2121.
  43. 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.
  44. Miles D, Gligorov J, André F, et al. IMpassion131 investigators. 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.
  45. Emens LA, Molinero L, Loi S, 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): 1005–1016.
  46. André F, Deurloo R, Qamra A, et al. Abstract PD10-05: Activity of atezolizumab (atezo) plus paclitaxel (pac) in metastatic triple-negative breast cancer (mTNBC) according to Burstein molecular subtype: Analysis of the IMpassion131 trial. Cancer Res. 2022; 82(4_Supplement): PD10-05-PD10–05.
  47. Loi S, Winer E, Lipatov O, et al. Abstract PD5-03: Relationship between tumor-infiltrating lymphocytes (TILs) and outcomes in the KEYNOTE-119 study of pembrolizumab vs chemotherapy for previously treated metastatic triple-negative breast cancer (mTNBC). Cancer Res. 2020; 80(4_Supplement): PD5-03-PD5–03.
  48. Modi S, Jacot W, Yamashita T, et al. DESTINY-Breast04 Trial Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. N Engl J Med. 2022; 387(1): 9–20.
  49. Daly MB, Pal T, Berry MP, et al. CGC, CGC, LCGC, CGC, CGC. Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2021; 19(1): 77–102.
  50. Tung N, Robson M, Ventz S, et al. TBCRC 048: A phase II study of olaparib monotherapy in metastatic breast cancer patients with germline or somatic mutations in DNA damage response (DDR) pathway genes (Olaparib Expanded). J Clin Oncol. 2020; 38(15_suppl): 1002–1002.
  51. Doraczyńska-Kowalik A, Janus-Szymańska G, Matkowski R, et al. Genetics and Oncology (part 2.). Fundamentals of personalised medicine in the treatment of breast and ovarian cancer. Nowotwory. Journal of Oncology. 2020; 70(5): 187–202.
  52. Kowalik A, Siołek M, Kopczyński J, et al. BRCA1 founder mutations and beyond in the Polish population: A single-institution BRCA1/2 next-generation sequencing study. PLoS One. 2018; 13(7): e0201086.
  53. Shvartsur A, Bonavida B. Trop2 and its overexpression in cancers: regulation and clinical/therapeutic implications. Genes Cancer. 2015; 6(3-4): 84–105.