Integrative review of clinical trials and meta-analysis of the main studies of neoadjuvant chemotherapy in the treatment of breast cancer in the past 30 years
Keywords:
breast neoplasms, neoadjuvant therapy, chemotherapyAbstract
Neoadjuvant chemotherapy (NAC) has become a common treatment strategy for early-stage breast cancer. In this study, we conducted a systematic research in the PubMed database using the following terms: breast cancer, neoadjuvant chemotherapy, randomized clinical trials, complete pathological response, overall survival, and disease-free survival. The research has been limited to articles published in the past 30 years (1993–2023). We included only randomized clinical trials that evaluated the use of NAC in breast cancer and data on PCR rates and survival outcomes. Our research resulted in a total of 13 randomized clinical trials and two meta-analyses. The PCR rates ranged from 13% to 58%, with higher rates observed in patients with triple-negative breast cancer (TNBC) and human epidermal growth factor 2 (HER-2+) disease. Several trials reveal a significant association between PCR and better survival results, including overall survival and disease-free survival. However, the impact of PCR on survival results was less consistent in patients with hormone receptor-positive breast cancer. The use of taxanes in combination with anthracyclines has been the most common NAC scheme evaluated in these trials. The PCR rates have been associated with better survival outcomes, in patients with TNBC and HER-2+ disease. However, the impact of PCR on survival outcomes in patients with hormone receptor-positive breast cancer is less clear. Additional studies are needed to determine the optimal NAC regimen for each subtype of breast cancer and to identify biomarkers that can predict the NAC response.
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References
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424. https://doi.org/10.3322/caac.21492
National Comprehensive Cancer Network. Breast cancer (Version 4.2023) [Internet]. [cited on 2023 May 10] Available from: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1419
von Minckwitz G, Untch M, Blohmer JU, Costa SD, Eidtmann H, Fasching PA, et al. Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol. 2012;30(15):1796-804. https://doi.org/10.1200/JCO.2011.38.8595
Symmans WF, Peintinger F, Hatzis C, Rajan R, Kuerer H, Valero V, et al. Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy. J Clin Oncol. 2007;25(7):4414-22. https://doi.org/10.1200/JCO.2007.10.6823
von Minckwitz G, Blohmer JU, Costa SD, Denkert C, Eidtmann H, Eiermann W, et al. Response-guided neoadjuvant chemotherapy for breast cancer. J Clin Oncol. 2013;31(4):3623-30. https://doi.org/10.1200/JCO.2012.45.0940
Esserman LJ, DeMichele A. Accelerated approval for pertuzumab in the neoadjuvant setting: winds of change? Clin Cancer Res. 2014;20(14):3632-6. https://doi.org/10.1158/1078-0432.CCR-13-3131
Carey LA, Winer EP. Defining success in neoadjuvant breast cancer trials. Lancet. 2014;384(9938):115-6. https://doi.org/10.1016/S0140-6736(14)60034-9
Leon-Ferre RA, Hieken TJ, Boughey JC. The landmark series: neoadjuvant chemotherapy for triple-negative and HER2-positive breast cancer. Ann Surg Oncol. 2021;28(4):2111-9. https://doi.org/10.1245/s10434-020-09480-9
Piltin MA, Hoskin TL, Day CN, Davis Jr J, Boughey JC. Oncologic outcomes of sentinel lymph node surgery after neoadjuvant chemotherapy for node-positive breast cancer. Ann Surg Oncol. 2020;27(12):4795-801. https://doi.org/10.1245/s10434-020-08900-0
Bonadonna G, Brusamolino E, Valagussa P, Rossi A, Brugnatelli L, Brambilla C, et al. Combination chemotherapy as an adjuvant treatment in operable breast cancer. N Engl J Med. 1976;294(8):405-10. https://doi.org/10.1056/NEJM197602192940801
Fisher B, Brown A, Mamounas E, Wieand S, Robidoux A, Margolese RG, et al. Effect of preoperative chemotherapy on local-regional disease in women with operable breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-18. J Clin Oncol. 1997;15(7):2483-93. https://doi.org/10.1200/JCO.1997.15.7.2483
Bear HD, Anderson S, Brown A, Smith R, Mamounas EP, Fisher B, et al. The effect on tumor response of adding sequential preoperative docetaxel to preoperative doxorubicin and cyclophosphamide: preliminary results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol. 2003;21(22):4165-74. https://doi.org/10.1200/JCO.2003.12.005
von Minckwitz G, Raab G, Caputo A, Schütte M, Hilfrich J, Blohmer JU, et al. Doxorubicin with cyclophosphamide followed by docetaxel every 21 days compared with doxorubicin and docetaxel every 14 days as preoperative treatment in operable breast cancer: the GEPARDUO study of the German Breast Group. J Clin Oncol. 2005;23(12):2676-85. https://doi.org/10.1200/JCO.2005.05.078
Ding Y, Ding K, Yang H, He X, Mo W, Ding X. 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. https://doi.org/10.1371/journal.pone.0234058
Li X, Dai D, Chen B, Tang H, Wei W. Oncological outcome of complete response after neoadjuvant chemotherapy for breast conserving surgery: a systematic review and meta-analysis. World J Surg Oncol. 2017;15(1):210. https://doi.org/10.1186/s12957-017-1273-6
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. 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
Buzdar AU, Ibrahim NK, Francis D, Booser DJ, Thomas ES, Theriault RL, et al. Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer. J Clin Oncol. 2005;23(16):3676-85. https://doi.org/10.1200/JCO.2005.07.032
Schneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, Hegg R, et al. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol. 2013;24(9):2278-84. https://doi.org/10.1093/annonc/mdt182
Gianni L, Pienkowski T, Im YH, Roman L, Tseng LM, Liu MC, et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012;13(1):25-32. https://doi.org/10.1016/S1470-2045(11)70336-9
van Ramshorst MS, van der Voort A, van Werkhoven ED, Mandjes IA, Kemper I, Dezentjé VO, et al. Neoadjuvant chemotherapy with or without anthracyclines in the presence of dual HER2 blockade for HER2-positive breast cancer (TRAIN-2): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2018;19(12):1630-40. https://doi.org/10.1016/S1470-2045(18)30570-9
Geyer CE, Sikov WM, Huober J, Rugo HS, Wolmark N, O'Shaughnessy 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):384-94. https://doi.org/10.1016/j.annonc.2022.01.009
von Minckwitz G, Schneeweiss A, Loibl S, Salat C, Denkert C, Rezai M, et al. Neoadjuvant carboplatin in patients with triple-negative and HER2-positive early breast cancer (GeparSixto; GBG 66): a randomised phase 2 trial. Lancet Oncol. 2014;15(7):747-56. https://doi.org/10.1016/S1470-2045(14)70160-3
Sikov WM, Berry DA, Perou CM, Singh B, Cirrincione CT, Tolaney SM, et al. Impact of the addition of carboplatin and/or bevacizumab to neoadjuvant once-per-week paclitaxel followed by dose-dense doxorubicin and cyclophosphamide on pathologic complete response rates in stage II to III triple-negative breast cancer: CALGB 40603 (Alliance). J Clin Oncol. 2015;33(1):13-21. https://doi.org/10.1200/JCO.2014.57.0572
Poggio F, Bruzzone M, Ceppi M, Pondé NF, La Valle G, Del Mastro L, et al. Platinum-based neoadjuvant chemotherapy in triple-negative breast cancer: a systematic review and meta-analysis. Ann Oncol. 2018;29(7):1497-508. https://doi.org/10.1093/annonc/mdy127
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. https://doi.org/10.1001/jamaoncol.2019.6650
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(9):810-21. https://doi.org/10.1056/NEJMoa1910549
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. https://doi.org/10.1016/S0140-6736(20)31953-X
Mancinelli BC, Antonini M, Silva FV, Ferraro O, Lopes RGC. Influence of breast cancer subtype on pathological complete response. Mastology. 2020;30:e20200007. https://doi.org/10.29289/25945394202020200007
Díaz-Casas SE, Castilla-Tarra JA, Pena-Torres E, Orozco-Ospino M, Mendoza-Diaz S, Nuñez-Lemus M, et al. Pathological response to neoadjuvant chemotherapy and the molecular classification of locally advanced breast cancer in a Latin American cohort. Oncologist. 2019;24(12):e1360-e70. https://doi.org/10.1634/theoncologist.2019-0300
Symmans WF, Peintinger F, Hatzis C, Rajan R, Kuerer H, Valero V, et al. Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy. J Clin Oncol. 2007;25(28):4414-22. https://doi.org/10.1200/JCO.2007.10.6823
Boughey JC, Ballman KV, McCall LM, Mittendorf EA, Symmans WF, Julian TB, et al. Tumor biology and response to chemotherapy impact breast cancer-specific survival in node-positive breast cancer patients treated with neoadjuvant chemotherapy: long-term follow-up from ACOSOG Z1071 (Alliance). Ann Surg. 2017;266(4):667-76. https://doi.org/10.1097/SLA.0000000000002373
Wolmark N, Wang J, Mamounas E, Bryant J, Fisher B. Preoperative chemotherapy in patients with operable breast cancer: nine-year results from National Surgical Adjuvant Breast and Bowel Project B-18. J Natl Cancer Inst Monogr. 2001(30):96-102. https://doi.org/10.1093/oxfordjournals.jncimonographs.a003469
Rastogi P, Anderson SJ, Bear HD, Geyer CE, Kahlenberg MS, Robidoux A, et al. Preoperative chemotherapy: updates of National Surgical Adjuvant Breast and Bowel Project Protocols B-18 and B-27. J Clin Oncol. 2008;26(5):778-85. https://doi.org/10.1200/JCO.2007.15.0235
Wolmark N, Wang J, Mamounas E, Bryant J, Fisher B. Preoperative chemotherapy in patients with operable breast cancer: nine-year results from National Surgical Adjuvant Breast and Bowel Project B-18. J Natl Cancer Inst Monogr. 2001(30):96-102. https://doi.org/10.1093/oxfordjournals.jncimonographs.a003469
van der Voort A, van Ramshorst MS, van Werkhoven ED, Mandjes IA, Kemper I, Vulink AJ, et al. Three-year follow-up of neoadjuvant chemotherapy with or without anthracyclines in the presence of dual erbb2 blockade in patients with erbb2-positive breast cancer: a secondary analysis of the TRAIN-2 randomized, phase 3 trial. JAMA Oncol. 2021;7(7):978-84. https://doi.org/10.1001/jamaoncol.2021.1371
Yee D, DeMichele AM, Yau C, Isaacs C, Symmans WF, Albain KS, et al. Association of event-free and distant recurrence-free survival with individual-level pathologic complete response in neoadjuvant treatment of stages 2 and 3 breast cancer: three-year follow-up analysis for the I-SPY2 adaptively randomized clinical trial. JAMA Oncol. 2020;6(9):1355-62. https://doi.org/10.1001/jamaoncol.2020.2535
Davey MG, Browne F, Miller N, Lowery AJ, Kerin MJ. Pathological complete response as a surrogate to improved survival in human epidermal growth factor receptor-2-positive breast cancer: systematic review and meta-analysis. BJS Open. 2022;6(3):zrac028. https://doi.org/10.1093/bjsopen/zrac028
Spring L, Greenup R, Niemierko A, Schapira L, Haddad S, Jimenez R, et al. Pathologic complete response after neoadjuvant chemotherapy and long-term outcomes among young women with breast cancer. J Natl Compr Canc Netw. 2017;15(10):1216-23. https://doi.org/10.6004/jnccn.2017.0158
Chaudry M, Lei X, Gonzalez-Angulo AM, Mittendorf EA, Valero V, Tripathy D, et al. Recurrence and survival among breast cancer patients achieving a pathological complete response to neoadjuvant chemotherapy. Breast Cancer Res Treat. 2015;153(2):417-23. https://doi.org/10.1007/s10549-015-3533-x
Litton JK, Rugo HS, Ettl J, Hurvitz SA, Gonçalves 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
von Minckwitz G, Huang CS, Mano MS, Loibl S, Mamounas EP, Untch M, et al. Trastuzumab emtansine for residual invasive HER2-positive breast cancer. N Engl J Med. 2019;380(7):617-28. https://doi.org/10.1056/NEJMoa1814017
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Copyright (c) 2024 Marcelo Antonini, André Mattar, Gabriel Duque Pannain, Luiz Henrique Gebrim, Odair Ferraro, Reginaldo Coelho Guedes Lopes, Juliana Monte Real
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