三阴性乳腺癌治疗模式及相关药物研究进展
Research Progress of Treatment Modalities and Related Drugs for Triple Negative Breast Cancer
DOI: 10.12677/acm.2024.1451654, PDF,   
作者: 刘永权：内蒙古医科大学第一临床医学院，内蒙古 呼和浩特；王 霞：内蒙古医科大学附属医院甲乳外科，内蒙古 呼和浩特
关键词: 三阴性乳腺癌；新辅助治疗；病理完全缓解；免疫治疗；预后；Triple Negative Breast Cancer； Neoadjuvant Therapy； Pathological Complete Response； Immunotherapy； Prognosis
摘要: 乳腺癌的病理分型中，三阴性乳腺癌(Triple negative breast cancer, TNBC)是一种具有高度侵袭性的分型，往往在确诊时即表现出较高的组织学分级以及较差的预后。如今新辅助治疗(Neoadjuvant Chemotherapy, NAC)作为临床上TNBC的主要治疗措施之一，其不仅一定程度上缓解了乳房和淋巴结区域的病变，使缺乏手术条件的患者得以手术，同时也显著改善了患者的长期预后。本文对三阴性乳腺癌患者常规治疗模式的选择以及化疗药物的进展等方面进行综述，为临床上此类病人的诊治提供参考。
Abstract: Among the pathological subtypes of breast cancer, triple-negative breast cancer (TNBC) is a highly aggressive subtype, which often shows higher histological grade and poor prognosis at the time of diagnosis. At present, neoadjuvant therapy (NAC) is one of the main treatment measures for TNBC in clinical practice, which not only alleviates the lesions in the breast and lymph node regions to a certain extent, enables patients who lack surgical conditions to undergo surgery, but also significantly improves the long-term prognosis of patients. This article reviews the selection of conventional treatment modalities and the progress of chemotherapy drugs for TNBC patients, so as to provide reference for the clinical diagnosis and treatment of such patients.
文章引用：刘永权, 王霞. 三阴性乳腺癌治疗模式及相关药物研究进展[J]. 临床医学进展, 2024, 14(5): 2083-2092. https://doi.org/10.12677/acm.2024.1451654

参考文献

[1] Sung, H., Ferlay, J., Siegel, R.L., et al. (2021) Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 71, 209-249. [Google Scholar] [CrossRef] [PubMed]
[2] Bianchini, G., De Angelis, C., Licata, L. and Gianni, L. (2022) Treatment Landscape of Triple-Negative Breast Cancer-Expanded Options, Evolving Needs. Nature Reviews Clinical Oncology, 19, 91-113. [Google Scholar] [CrossRef] [PubMed]
[3] Dent, R., Trudeau, M., Pritchard, K.I., et al. (2007) Triple-Negative Breast Cancer: Clinical Features and Patterns of Recurrence. Clinical Cancer Research, 13, 4429-4434. [Google Scholar] [CrossRef] 
[4] Perou, C.M., Sørlie, T., Eisen, M.B., et al. (2000) Molecular Portraits of Human Breast Tumours. Nature, 406, 747-752. [Google Scholar] [CrossRef] [PubMed]
[5] Lehmann, B.D., Bauer, J.A., Chen, X., et al. (2011) Identification of Human Triple-Negative Breast Cancer Subtypes and Preclinical Models for Selection of Targeted Therapies. Journal of Clinical Investigation, 121, 2750-2767.
[6] Lehmann, B.D., Jovanović, B., Chen, X., et al. (2016) Refinement of Triple-Negative Breast Cancer Molecular Subtypes: Implications for Neoadjuvant Chemotherapy Selection. PLOS ONE, 11, e0157368. [Google Scholar] [CrossRef] [PubMed]
[7] Masuda, H., Baggerly, K.A., Wang, Y., et al. (2013) Differential Response to Neoadjuvant Chemotherapy among 7 Triple-Negative Breast Cancer Molecular Subtypes. Clinical Cancer Research, 19, 5533-5540. [Google Scholar] [CrossRef] 
[8] 孙晓萌. 三阴性乳腺癌的临床治疗现状及新进展[J]. 实用癌症杂志, 2020, 35(6): 1037-1039.
[9] van den Ende, N.S., Nguyen, A.H., Jager, A., Kok, M., Debets, R. and van Deurzen, C.H.M. (2023) Triple-Negative Breast Cancer and Predictive Markers of Response to Neoadjuvant Chemotherapy: A Systematic Review. International Journal of Molecular Sciences, 24, Article 2969. [Google Scholar] [CrossRef] [PubMed]
[10] Del Prete, S., Caraglia, M., Luce, A., et al. (2019) Clinical and Pathological Factors Predictive of Response to Neoadjuvant Chemotherapy in Breast Cancer: A Single Center Experience. Oncology Letters, 18, 3873-3879. [Google Scholar] [CrossRef] [PubMed]
[11] von Minckwitz, G., Untch, M., Blohmer, J.-U., et al. (2012) Definition and Impact of Pathologic Complete Response on Prognosis after Neoadjuvant Chemotherapy in Various Intrinsic Breast Cancer Subtypes. Journal of Clinical Oncology, 30, 1796-1804. [Google Scholar] [CrossRef] 
[12] Rouzier, R., Perou, C.M., Symmans, W.F., et al. (2005) Breast Cancer Molecular Subtypes Respond Differently to Preoperative Chemotherapy. Clinical Cancer Research, 11, 5678-5685. [Google Scholar] [CrossRef] 
[13] Liedtke, C., Mazouni, C., Hess, K.R., et al. (2023) Response to Neoadjuvant Therapy and Long-Term Survival in Patients with Triple-Negative Breast Cancer. Journal of Clinical Oncology, 41, 1809-1815. [Google Scholar] [CrossRef] 
[14] Rastogi, P., anderson, S.J., Bear, H.D., et al. (2008) Preoperative Chemotherapy: Updates of National Surgical Adjuvant Breast and Bowel Project Protocols B-18 and B-27. Journal of Clinical Oncology, 26, 778-785. [Google Scholar] [CrossRef] 
[15] Schettini, F., Giuliano, M., De Placido, S. and Arpino, G. (2016) Nab-Paclitaxel for the Treatment of Triple-Negative Breast Cancer: Rationale, Clinical Data and Future Perspectives. Cancer Treatment Reviews, 50, 129-141. [Google Scholar] [CrossRef] [PubMed]
[16] 张雪琛. FAC和TEC新辅助化疗方案在乳腺癌患者治疗中的效果对比[J]. 中国卫生标准管理, 2020, 11(23): 101-102.
[17] Untch, M., Jackisch, C., Schneeweiss, A., et al. (2019) NAB-Paclitaxel Improves Disease-Free Survival in Early Breast Cancer: GBG 69-GeparSepto. Journal of Clinical Oncology, 37, 2226-2234. [Google Scholar] [CrossRef] 
[18] Twelves, C., Wong, A., Nowacki, M.P., et al. (2005) Capecitabine as Adjuvant Treatment for Stage III Colon Cancer. The New England Journal of Medicine, 352, 2696-2704. [Google Scholar] [CrossRef] 
[19] Masuda, N., Lee, S.-J., Ohtani, S., et al. (2017) Adjuvant Capecitabine for Breast Cancer after Preoperative Chemotherapy. The New England Journal of Medicine, 376, 2147-2159. [Google Scholar] [CrossRef] 
[20] Lluch, A., Barrios, C.H., Torrecillas, L., Ruiz-Borrego, M., Bines, J., et al. (2020) Phase III Trial of Adjuvant Capecitabine after Standard Neo-/Adjuvant Chemotherapy in Patients with Early Triple-Negative Breast Cancer (GEICAM/2003-11_CIBOMA/2004-01). Journal of Clinical Oncology, 38, 203-213. [Google Scholar] [CrossRef] 
[21] Garutti, M., Pelizzari, G., Bartoletti, M., et al. (2019) Platinum Salts in Patients with Breast Cancer: A Focus on Predictive Factors. International Journal of Molecular Sciences, 20, Article 3390. [Google Scholar] [CrossRef] [PubMed]
[22] Byrski, T., Gronwald, J., Huzarski, T., et al. (2010) Pathologic Complete Response Rates in Young Women with BRCA1-Positive Breast Cancers after Neoadjuvant Chemotherapy. Journal of Clinical Oncology, 28, 375-379. [Google Scholar] [CrossRef] 
[23] Alba, E., Chacon, J.I., Lluch, A., et al. (2012) A Randomized Phase II Trial of Platinum Salts in Basal-Like Breast Cancer Patients in the Neoadjuvant Setting. Results from the GEICAM/2006-03, Multicenter Study. Breast Cancer Research and Treatment, 136, 487-493. [Google Scholar] [CrossRef] [PubMed]
[24] von Minckwitz, G., Schneeweiss, A., Loibl, S., et al. (2014) Neoadjuvant Carboplatin in Patients with Triple-Negative and HER2-Positive Early Breast Cancer (GeparSixto; GBG 66): A Randomised Phase 2 Trial. The Lancet Oncology, 15, 747-756. [Google Scholar] [CrossRef] 
[25] Sikov, W.M., Berry, D.A., Perou, C.M., et al. (2015) 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). Journal of Clinical Oncology, 33, 13-21. [Google Scholar] [CrossRef] 
[26] Zhang, P., Yin, Y., Mo, H., et al. (2016) Better Pathologic Complete Response and Relapse-Free Survival after Carboplatin Plus Paclitaxel Compared with Epirubicin Plus Paclitaxel as Neoadjuvant Chemotherapy for Locally Advanced Triple-Negative Breast Cancer: A Randomized Phase 2 Trial. Oncotarget, 7, 60647-60656. [Google Scholar] [CrossRef] [PubMed]
[27] Zhang, L., Wu, Z.-Y., Li, J., et al. (2022) Neoadjuvant Docetaxel Plus Carboplatin vs Epirubicin Plus Cyclophosphamide Followed by Docetaxel in Triple-Negative, Early-Stage Breast Cancer (NeoCART): Results from a Multicenter, Randomized Controlled, Open-Label Phase II Trial. International Journal of Cancer, 150, 654-662. [Google Scholar] [CrossRef] [PubMed]
[28] Desai, A.P., Chengappa, M., Go, R.S. and Poonacha, T.K. (2020) Financial Conflicts of Interest among National Comprehensive Cancer Network Clinical Practice Guideline Panelists in 2019. Cancer, 126, 3742-3749. [Google Scholar] [CrossRef] [PubMed]
[29] Shah, S.P., Roth, A., Goya, R., Oloumi, A., et al. (2012) The Clonal and Mutational Evolution Spectrum of Primary Triple-Negative Breast Cancers. Nature, 486, 395-399. [Google Scholar] [CrossRef] [PubMed]
[30] Khosravi-Shahi, P., Cabezón-Gutiérrez, L. and Custodio-Cabello, S. (2018) Metastatic Triple Negative Breast Cancer: Optimizing Treatment Options, New and Emerging Targeted Therapies. Asia-Pacific Journal of Clinical Oncology, 14, 32-39. [Google Scholar] [CrossRef] [PubMed]
[31] Asano, Y., Kashiwagi, S., Goto, W., et al. (2018) Prediction of Treatment Responses to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer by Analysis of Immune Checkpoint Protein Expression. Journal of Translational Medicine, 16, Article No. 87. [Google Scholar] [CrossRef] [PubMed]
[32] Liu, Z., Li, M., Jiang, Z. and Wang, X. (2018) A Comprehensive Immunologic Portrait of Triple-Negative Breast Cancer. Translational Oncology, 11, 311-329. [Google Scholar] [CrossRef] [PubMed]
[33] Schmid, P., Salgado, R., Park, Y.H., et al. (2020) Pembrolizumab Plus Chemotherapy as Neoadjuvant Treatment of High-Risk, Early-Stage Triple-Negative Breast Cancer: Results from the Phase 1b Open-Label, Multicohort KEYNOTE-173 Study. Annals of Oncology, 31, 569-581. [Google Scholar] [CrossRef] [PubMed]
[34] Nanda, R., Liu, M.C., Yau, C., et al. (2020) 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 Oncology, 6, 676-684. [Google Scholar] [CrossRef] [PubMed]
[35] Schmid, P., Cortes, J., Pusztai, L., et al. (2020) Pembrolizumab for Early Triple-Negative Breast Cancer. The New England Journal of Medicine, 382, 810-821. [Google Scholar] [CrossRef] 
[36] Hosseini, A., Gharibi, T., Marofi, F., Babaloo, Z. and Baradaran, B. (2020) CTLA-4: From Mechanism to Autoimmune Therapy. International Immunopharmacology, 80, Article 106221. [Google Scholar] [CrossRef] [PubMed]
[37] Postow, M.A., Chesney, J., Pavlick, A.C., et al. (2015) Nivolumab and Ipilimumab versus Ipilimumab in Untreated Melanoma. The New England Journal of Medicine, 372, 2006-2017. [Google Scholar] [CrossRef] 
[38] Liu, L., Wang, Y., Miao, L., et al. (2018) Combination Immunotherapy of MUC1 mRNA Nano-Vaccine and CTLA-4 Blockade Effectively Inhibits Growth of Triple Negative Breast Cancer. Molecular Therapy, 26, 45-55. [Google Scholar] [CrossRef] [PubMed]
[39] Bernier, C., Soliman, A., Gravel, M., et al. (2018) DZ-2384 Has a Superior Preclinical Profile to Taxanes for the Treatment of Triple-Negative Breast Cancer and Is Synergistic with Anti-CTLA-4 Immunotherapy. Anti-Cancer Drugs, 29, 774-785. [Google Scholar] [CrossRef] 
[40] Nguyen, V.P., Campbell, K.M., Nowicki, T.S., et al. (2023) A Pilot Study of Neoadjuvant Nivolumab, Ipilimumab, and Intralesional Oncolytic Virotherapy for HER2-Negative Breast Cancer. Cancer Research Communications, 3, 1628-1637. [Google Scholar] [CrossRef] 
[41] Han, Y., Yu, X., Li, S., Tian, Y. and Liu, C. (2020) New Perspectives for Resistance to PARP Inhibitors in Triple-Negative Breast Cancer. Frontiers in Oncology, 10, Article 578095. [Google Scholar] [CrossRef] [PubMed]
[42] Robson, M., Im, S.A., Senkus, E., et al. (2017) Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation. The New England Journal of Medicine, 377, 523-533. [Google Scholar] [CrossRef] 
[43] Gelmon, K.A., Tischkowitz, M., Mackay, H., et al. (2011) Olaparib in Patients with Recurrent High-Grade Serous or Poorly Differentiated Ovarian Carcinoma or Triple-Negative Breast Cancer: A Phase 2, Multicentre, Open-Label, Non-Randomised Study. The Lancet Oncology, 12, 852-861. [Google Scholar] [CrossRef] 
[44] Ayoub, J.-P., Wildiers, H., Friedlander, M., et al. (2021) Safety and Efficacy of Veliparib plus Carboplatin/Paclitaxel in Patients with HER2-Negative Metastatic or Locally Advanced Breast Cancer: Subgroup Analyses by Germline BRCA1/2 Mutations and Hormone Receptor Status from the Phase-3 BROCADE3 Trial. Therapeutic Advances in Medical Oncology, 13, 17588359211059601. [Google Scholar] [CrossRef] [PubMed]
[45] Vinayak, S., Tolaney, S.M., Schwartzberg, L., et al. (2019) Open-Label Clinical Trial of Niraparib Combined with Pembrolizumab for Treatment of Advanced or Metastatic Triple-Negative Breast Cancer. JAMA Oncology, 5, 1132-1140. [Google Scholar] [CrossRef] [PubMed]
[46] von Minckwitz, G. and Martin, M. (2012) Neoadjuvant Treatments for Triple-Negative Breast Cancer (TNBC). Annals of Oncology, 23, VI35-VI39. [Google Scholar] [CrossRef] [PubMed]
[47] Bear, H.D., Tang, G., Rastogi, P., et al. (2012) Bevacizumab Added to Neoadjuvant Chemotherapy for Breast Cancer. The New England Journal of Medicine, 366, 310-320. [Google Scholar] [CrossRef] 
[48] Livasy, C.A., Karaca, G., Nanda, R., et al. (2006) Phenotypic Evaluation of the Basal-Like Subtype of Invasive Breast Carcinoma. Modern Pathology, 19, 264-271. [Google Scholar] [CrossRef] [PubMed]
[49] Carey, L.A., Rugo, H.S., Marcom, P.K., et al. (2012) TBCRC 001: Randomized Phase II Study of Cetuximab in Combination with Carboplatin in Stage IV Triple-Negative Breast Cancer. Journal of Clinical Oncology, 30, 2615-2623. [Google Scholar] [CrossRef] 
[50] Tao, J.J., Castel, P., Radosevic-Robin, N., et al. (2014) Antagonism of EGFR and HER3 Enhances the Response to Inhibitors of the PI3K-Akt Pathway in Triple-Negative Breast Cancer. Science Signaling, 7, ra29. [Google Scholar] [CrossRef] [PubMed]
[51] Massihnia, D., Perez, A., Bazan, V., et al. (2016) A Headlight on Liquid Biopsies: A Challenging Tool for Breast Cancer Management. Tumor Biology, 37, 4263-4273. [Google Scholar] [CrossRef] [PubMed]
[52] Schmid, P., Abraham, J., Chan, S., et al. (2020) Capivasertib Plus Paclitaxel versus Placebo Plus Paclitaxel as First-Line Therapy for Metastatic Triple-Negative Breast Cancer: The PAKT Trial. Journal of Clinical Oncology, 38, 423-433. [Google Scholar] [CrossRef] 
[53] Oliveira, M., Saura, C., Nuciforo, P., et al. (2019) FAIRLANE, a Double-Blind Placebo-Controlled Randomized Phase II Trial of Neoadjuvant Ipatasertib Plus Paclitaxel for Early Triple-Negative Breast Cancer. Annals of Oncology, 30, 1289-1297. [Google Scholar] [CrossRef] [PubMed]
[54] Chu, Y., Zhou, X. and Wang, X. (2021) Antibody-Drug Conjugates for the Treatment of Lymphoma: Clinical Advances and Latest Progress. Journal of Hematology & Oncology, 14, Article No. 88. [Google Scholar] [CrossRef] [PubMed]
[55] Jeon, Y., Jo, U., Hong, J., Gong, G. and Lee, H.J. (2022) Trophoblast Cell-Surface Antigen 2 (TROP2) Expression in Triple-Negative Breast Cancer. BMC Cancer, 22, Article No. 1014. [Google Scholar] [CrossRef] [PubMed]
[56] Cortesi, M., Zanoni, M., Maltoni, R., et al. (2022) TROP2 (Trophoblast Cell-Surface Antigen 2): A Drug Target for Breast Cancer. Expert Opinion on Therapeutic Targets, 26, 593-602. [Google Scholar] [CrossRef] [PubMed]
[57] 邵笛, 余天剑, 邵志敏. 三阴性乳腺癌精准治疗研究进展[J]. 中国普通外科杂志, 2023, 32(11): 1629-1638.
[58] Rizzo, A., Cusmai, A., Acquafredda, S., Rinaldi, L. and Palmiotti, G. (2022) Ladiratuzumab Vedotin for Metastatic Triple Negative Cancer: Preliminary Results, Key Challenges, and Clinical Potential. Expert Opinion on Investigational Drugs, 31, 495-498. [Google Scholar] [CrossRef] [PubMed]
[59] McGuinness, J.E. and Kalinsky, K. (2021) Antibody-Drug Conjugates in Metastatic Triple Negative Breast Cancer: A Spotlight on Sacituzumab Govitecan, Ladiratuzumab Vedotin, and Trastuzumab Deruxtecan. Expert Opinion on Biological Therapy, 21, 903-913. [Google Scholar] [CrossRef] [PubMed]
[60] Okajima, D., Yasuda, S., Maejima, T., et al. (2021) Datopotamab Deruxtecan, a Novel TROP2-Directed Antibody-Drug Conjugate, Demonstrates Potent Antitumor Activity by Efficient Drug Delivery to Tumor Cells. Molecular Cancer Therapeutics, 20, 2329-2340. [Google Scholar] [CrossRef] 
[61] Cortés, J., Kim, S.-B., Chung, W.-P., et al. (2022) Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer. The New England Journal of Medicine, 386, 1143-1154. [Google Scholar] [CrossRef] 
[62] Hurvitz, S.A., Hegg, R., Chung, W.P., et al. (2023) Trastuzumab Deruxtecan versus Trastuzumab Emtansine in Patients with HER2-Positive Metastatic Breast Cancer: Updated Results from DESTINY-Breast03, a Randomised, Open-Label, Phase 3 Trial. The Lancet, 401, 105-117. [Google Scholar] [CrossRef] 
[63] Modi, S., Jacot, W., Yamashita, T., et al. (2022) Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. The New England Journal of Medicine, 387, 9-20. [Google Scholar] [CrossRef] 

为你推荐