三阴性乳腺癌新辅助治疗现状

doi:10.3969/j.issn.1009-976X.2022.02.017

摘要/Abstract

摘要： 目的三阴性乳腺癌高侵袭、高复发、高转移且预后差,对内分泌治疗、抗Her-2靶向治疗不敏感。本研究总结了近年来三阴性乳腺癌新辅助治疗进展。方法应用PubMed、CNKI、万方等数据库,以“TNBC、新辅助治疗、病理完全缓解”等作为搜索关键词,检索近年的相关文献。结果病理完全缓解被认为是新辅助治疗预后评判的重要标准之一。蒽环类联合紫杉类药物仍然是TNBC患者的首选新辅助化疗方案,铂类药物的应用使BRCA基因突变TNBC患者有了更优的新辅助化疗方案,但血液学、消化系统等相关不良反应不可忽视。免疫调定点抑制剂相关药物被证实在TNBC新辅助治疗上能提高pCR,改善长期生存预后,且因药物不良反应停药较铂类药物发生率更低。肿瘤微环境靶向药物、多聚ADP核糖聚合酶抑制剂、PI3K/AKT/mTOR通路抑制剂等相关药物在多药联合方面上的临床研究有积极治疗效果。结论 TNBC新辅助治疗中,化疗是基础,免疫治疗已有相关临床试验成果,肿瘤微环境靶向药物、多聚ADP核糖聚合酶抑制剂、PI3K/AKT/mTOR通路抑制剂具有很大研究前景。

关键词: 三阴性乳腺癌, 新辅助治疗, 病理完全缓解

Abstract: Objective Triple negative breast cancer has high invasion, high recurrence, high metastasis and poor prognosis,and it has poor effect on endocrine therapy and anti-HER-2 targeted therapy.This study summarized the progress of neoadjuvant therapy for triple negative breast cancer in recent years. Methods PubMed, CNKI, Wanfang and other databases were used to search relevant literatures in recent years with “TNBC, neoadjuvant therapy, pathological complete response” as search keywords. Results Pathological complete response rate is considered to be one of the important criteria for the prognosis of neoadjuvant therapy. Anthracycline combined with paclitaxel is still the preferred neoadjuvant chemotherapy regimen for TNBC patients. Platinum-based drugs provide a better neoadjuvant chemotherapy regimen for TNBC patients with BRCA gene mutation, but hematological and digestive adverse reactions need to be paid attention to. Drugs related to immune check point inhibitors have been proved to enhance pCR and improve long-term survival prognosis in TNBC neoadjuvant therapy, and discontinuation due to adverse drug reactions has a lower incidence than platinum drugs. In addition, the tumor microenvironment targeting drugs, poly ADP ribose polymerase inhibitors, PI3K/AKT/mTOR pathway inhibitors and other related drugs have positive therapeutic effects in clinical studies on multi-drug combination. Conclusion In the neoadjuvant therapy of TNBC, chemotherapy is the basis, and immunotherapy has achieved relevant clinical trial results. Tumor microenvironment targeting drugs, PARP inhibitors, and PI3K/AKT/mTOR pathway inhibitors have great research prospects.

Key words: triple-negative breast cancer, neoadjuvant therapy, pathological complete response

中图分类号:

R737.9

曾智豪, 何深. 三阴性乳腺癌新辅助治疗现状[J]. 岭南现代临床外科, 2022, 22(02): 205-209.

ZENG Zhi-hao, HE Shen. Current situation of neoadjuvant therapy for triple negative breast cancer[J]. Lingnan Modern Clinics In Surgery, 2022, 22(02): 205-209.

参考文献

[1] Harbeck N, Gnant M.Breast cancer[J]. Lancet, 2017, 389(10074): 1134-1150.
[2] Santonja A, Sánchez-Muñoz A, Lluch A, et al.Triple negative breast cancer subtypes and pathologic complete response rate to neoadjuvant chemotherapy[J]. Oncotarget, 2018, 9(41): 26406-26416.
[3] Sikov WM, Berry DA, Perou CM, 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]. J Clin Oncol, 2015, 33(1): 13-21.
[4] Parsons HA, Burstein HJ.Adjuvant Capecitabine in Triple-Negative Breast Cancer: New Strategies for Tailoring Treatment Recommendations[J]. JAMA, 2021, 325(1): 36-38.
[5] Huang M, O′Shaughnessy J, Zhao J, et al. Association of Pathologic Complete Response with Long-Term Survival Outcomes in Triple-Negative Breast Cancer: A Meta-Analysis[J]. Cancer Res, 2020, 80(24): 5427-5434.
[6] 黄艳. 铂类在新辅助化疗治疗三阴性乳腺癌的疗效及安全性的荟萃分析[D]. 重庆医科大学, 2020.
[7] von Minckwitz G, Schneeweiss A, Loibl S, et al. Neoadjuvant carboplatin in patients with triple-negative and HER2-positive early breast cancer (GeparSixto; GBG 66): a randomised phase 2 trial[J]. Lancet Oncol, 2014, 15(7): 747-756.
[8] Castrellon AB, Velez M, Nguyen SM, et al.Evaluation of weekly paclitaxel plus carboplatin followed by anthracycline chemotherapy on the neoadjuvant treatment of patients with triple-negative breast cancer[J]. Hematol Oncol Stem Cell Ther, 2018, 11(1): 30-33.
[9] Miyashita H, Satoi S, Cruz C, Malamud SC.Neo-adjuvant therapy for triple-negative breast cancer: Insights from a network meta-analysis[J]. Breast J, 2020, 26(9): 1717-1728.
[10] 王楠, 李鹍, 李惠平, 等. 铂类化疗药物对进展期三阴性乳腺癌的临床疗效及与BRCA基因突变的关系[J]. 癌症进展, 2019. 17(4): 419-422+438.
[11] 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[J]. BMC Cancer, 2019, 19(1): 1065.
[12] Mittendorf EA, Philips AV, Meric-Bernstam F, et al.PD-L1 expression in triple-negative breast cancer[J]. Cancer Immunol Res, 2014, 2(4): 361-370.
[13] Ghebeh H, Mohammed S, Al-Omair A, et al.The B7-H1 (PD-L1) T lymphocyte-inhibitory molecule is expressed in breast cancer patients with infiltrating ductal carcinoma: correlation with important high-risk prognostic factors[J]. Neoplasia, 2006, 8(3): 190-198.
[14] Schmid P, Adams S, Rugo HS, et al.IMpassion130 Trial Investigators. Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer[J]. N Engl J Med, 2018, 379(22): 2108-2121.
[15] 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[J]. Lancet, 2020, 396(10257): 1090-1100.
[16] Soliman H, Khalil F, Antonia S.PD-L1 expression is increased in a subset of basal type breast cancer cells[J]. PLoS One, 2014, 9(2): e88557.
[17] Loibl S, Untch M, Burchardi N, 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[J]. Ann Oncol, 2019, 30(8): 1279-1288.
[18] Denkert C, von Minckwitz G, Darb-Esfahani S, et al. Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy[J]. Lancet Oncol, 2018, 19(1): 40-50.
[19] 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[J]. Front Oncol, 2021, 11: 693542.
[20] Fan Y, He S.The Characteristics of Tumor Microenvironment in Triple Negative Breast Cancer[J]. Cancer Manag Res, 2022, 14: 1-17.
[21] Pan Y, Yu Y, Wang X, Zhang T.Tumor-Associated Macrophages in Tumor Immunity[J]. Front Immunol, 2020, 11: 583084.
[22] Xun Q, Wang Z, Hu X, et al.Small-Molecule CSF1R Inhibitors as Anticancer Agents[J]. Curr Med Chem, 2020, 27(23): 3944-3966.
[23] 王斌, 杨艳, 姜战胜. BRCA突变乳腺癌的临床研究进展[J]. 中国肿瘤临床, 2021, 48(17): 906-909.
[24] Rugo HS, Olopade OI, DeMichele A, et al. Adaptive Randomization of Veliparib-Carboplatin Treatment in Breast Cancer[J]. N Engl J Med, 2016, 375(1): 23-34.
[25] 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[J]. Lancet Oncol, 2018, 19(4): 497-509.
[26] Oliveira M, Saura C, Nuciforo P, et al.FAIRLANE, a double-blind placebo-controlled randomized phase II trial of neoadjuvant ipatasertib plus paclitaxel for early triple-negative breast cancer[J]. Ann Oncol, 2019, 30(8): 1289-1297.
[27] Anand K, Patel T, Niravath P, et al.Targeting mTOR and DNA repair pathways in residual triple negative breast cancer post neoadjuvant chemotherapy[J]. Sci Rep, 2021,11(1): 82.