New research advances and future prospect in precision treatment of triple-negative breast cancer

doi:10.19401/j.cnki.1007-3639.2022.08.001

Abstract

Abstract:

According to the latest data released by the Cancer Research Institute of the World Health Organization, breast cancer has replaced lung cancer as the malignant tumor with the highest incidence rate in the world. Triple-negative breast cancer (TNBC) is defined by a lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Compared with other types of breast cancer, TNBC bears the characteristics of high metastasis rate, strong invasiveness and poor prognosis. TNBC is not sensitive to endocrine therapy and anti-HER2 therapy, and chemotherapy is its main systemic treatment. With the vigorous development of genomics, transcriptomics, metabolomics, proteomics, microbiomics technologies and the in-depth study of TNBC molecular subtyping, targeted therapy and immunotherapy drugs, including poly(ADP-ribose) polymerase (PARP) inhibitors, trophoblast cell-surface antigen 2 (TROP-2) antibody-drug conjugate, pembrolizumab, atezolizumab, durvalumab, etc., have provided new therapeutic methods, which are changing the clinical practice and treatment pattern of TNBC. It is believed accurate therapy will become a new direction of development in the future. Based on the molecular subtypes of TNBC, here we summarized the research advances in targeted therapy and immunotherapy of TNBC, in order to provide reference for the precise treatment strategy of TNBC in the future.

Key words: Triple-negative breast cancer, Molecular subtypes, Precision therapy, Targeted therapy, Immunotherapy

CLC Number:

R737.9

XIAO Yuling, ZHU Xiuzhi, JIANG Yizhou, SHAO Zhimin. New research advances and future prospect in precision treatment of triple-negative breast cancer[J]. China Oncology, 2022, 32(8): 669-679.

References 83

[1]	SUNG H, FERLAY J, SIEGEL R L, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249. doi: 10.3322/caac.21660
[2]	JIANG Y Z, MA D, SUO C, et al. Genomic and transcriptomic landscape of triple-negative breast cancers: subtypes and treatment strategies[J]. Cancer Cell, 2019, 35(3): 428-440.e5. doi: 10.1016/j.ccell.2019.02.001
[3]	CHO B, HAN Y N, LIAN M, et al. Evaluation of racial/ethnic differences in treatment and mortality among women with triple-negative breast cancer[J]. JAMA Oncol, 2021, 7(7): 1016-1023. doi: 10.1001/jamaoncol.2021.1254
[4]	YIN L, DUAN J J, BIAN X W, et al. Triple-negative breast cancer molecular subtyping and treatment progress[J]. Breast Cancer Res, 2020, 22(1): 61. doi: 10.1186/s13058-020-01296-5
[5]	LEHMANN B D, BAUER J A, CHEN X, et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies[J]. J Clin Invest, 2011, 121(7): 2750-2767. doi: 10.1172/JCI45014
[6]	LEHMANN B D, JOVANOVIĆ B, CHEN X, et al. Refinement of triple-negative breast cancer molecular subtypes: implications for neoadjuvant chemotherapy selection[J]. PLoS One, 2016, 11(6): e0157368.
[7]	BURSTEIN M D, TSIMELZON A, POAGE G M, et al. Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer[J]. Clin Cancer Res, 2015, 21(7): 1688-1698. doi: 10.1158/1078-0432.CCR-14-0432
[8]	ZHAO S, MA D, XIAO Y, et al. Molecular subtyping of triple-negative breast cancers by immunohistochemistry: molecular basis and clinical relevance[J]. Oncologist, 2020, 25(10): e1481-e1491.
[9]	JIANG Y Z, LIU Y, XIAO Y, et al. Molecular subtyping and genomic profiling expand precision medicine in refractory metastatic triple-negative breast cancer: the FUTURE trial[J]. Cell Res, 2021, 31(2): 178-186. doi: 10.1038/s41422-020-0375-9
[10]	CHEN L, JIANG Y Z, WU S Y, et al. Famitinib with camrelizumab and nab-paclitaxel for advanced immunomodulatory triple-negative breast cancer (FUTURE-C-plus): an open-label, single-arm, phase Ⅱ trial[J]. Clin Cancer Res, 2022, 28(13): 2807-2817. doi: 10.1158/1078-0432.CCR-21-4313
[11]	WU S Y, XU Y, CHEN L, et al. Combined angiogenesis and PD-1 inhibition for immunomodulatory TNBC: concept exploration and biomarker analysis in the FUTURE-C-Plus trial[J]. Mol Cancer, 2022, 21(1): 84. doi: 10.1186/s12943-022-01536-6
[12]	NOORDERMEER S M, VAN ATTIKUM H. PARP inhibitor resistance: a tug-of-war in BRCA-mutated cells[J]. Trends Cell Biol, 2019, 29(10): 820-834. doi: 10.1016/j.tcb.2019.07.008
[13]	CORTESI L, RUGO H S, JACKISCH C. An overview of PARP inhibitors for the treatment of breast cancer[J]. Target Oncol, 2021, 16(3): 255-282. doi: 10.1007/s11523-021-00796-4
[14]	ROBSON M, IM S A, SENKUS E, et al. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation[J]. N Engl J Med, 2017, 377(6): 523-533. doi: 10.1056/NEJMoa1706450
[15]	ROBSON M E, 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[J]. Ann Oncol, 2019, 30(4): 558-566. doi: 10.1093/annonc/mdz012
[16]	TUTT A N J, GARBER J, GELBER R D, et al. VP1-2022: pre-specified event driven analysis of overall survival (OS) in the OlympiA phase Ⅲ trial of adjuvant olaparib (OL) in germline BRCA1/2 mutation (gBRCAm) associated breast cancer[J]. Ann Oncol, 2022, 33(5): 566-568. doi: 10.1016/j.annonc.2022.03.008
[17]	TUTT A N J, GARBER J E, KAUFMAN B, et al. Adjuvant olaparib for patients with BRCA1- or BRCA2-mutated breast cancer[J]. N Engl J Med, 2021, 384(25): 2394-2405. doi: 10.1056/NEJMoa2105215
[18]	MCGUIRE K P, ARTHUR D W, MAMOUNAS E P. Updates on management of hereditary breast cancer: new data on PARP inhibitors change recommendations regarding the multidisciplinary care of breast cancer patients with BRCA mutations[J]. Ann Surg Oncol, 2022: 2022Jun18.
[19]	LITTON J K, RUGO H S, ETTL J, et al. Talazoparib in patients with advanced breast cancer and a germline BRCA mutation[J]. N Engl J Med, 2018, 379(8): 753-763. doi: 10.1056/NEJMoa1802905
[20]	LITTON J K, BECK J T, JONES J M, 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[J]. J Clin Oncol, 2021, 39(15_suppl): 505. doi: 10.1016/S0959-8049(02)00743-8
[21]	KHOURY K, FELDMAN R, POHLMANN P R, et al. Molecular characterization of trophoblast cell surface antigen 2 (Trop-2) positive triple negative breast cancer (TNBC)[J]. J Clin Oncol, 2019, 37(15_suppl): e14651.
[22]	VRANIC S, GATALICA Z. Trop-2 protein as a therapeutic target: a focused review on Trop-2-based antibody-drug conjugates and their predictive biomarkers[J]. Bosn J Basic Med Sci, 2022, 22(1): 14-21.
[23]	BARDIA A, MAYER I A, VAHDAT L T, et al. Sacituzumab govitecan-hziy in refractory metastatic triple-negative breast cancer[J]. N Engl J Med, 2019, 380(8): 741-751. doi: 10.1056/NEJMoa1814213
[24]	WAHBY S, FASHOYIN-AJE L, OSGOOD C L, et al. FDA approval summary: accelerated approval of sacituzumab govitecan-hziy for third-line treatment of metastatic triple-negative breast cancer[J]. Clin Cancer Res, 2021, 27(7): 1850-1854. doi: 10.1158/1078-0432.CCR-20-3119
[25]	BARDIA A, TOLANEY S M, 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[J]. Ann Oncol, 2021, 32(9): 1148-1156. doi: 10.1016/j.annonc.2021.06.002
[26]	BARDIA A, HURVITZ S A, TOLANEY S M, et al. Sacituzumab govitecan in metastatic triple-negative breast cancer[J]. N Engl J Med, 2021, 384(16): 1529-1541. doi: 10.1056/NEJMoa2028485
[27]	MIRICESCU D, TOTAN A, STANESCU-SPINU I I, et al. PI3K/AKT/mTOR signaling pathway in breast cancer: from molecular landscape to clinical aspects[J]. Int J Mol Sci, 2020, 22(1): E173.
[28]	JANKU F, YAP T A, MERIC-BERNSTAM F. Targeting the PI3K pathway in cancer: are we making headway?[J]. Nat Rev Clin Oncol, 2018, 15(5): 273-291. doi: 10.1038/nrclinonc.2018.28
[29]	AGOSTINETTO E, EIGER D, PUNIE K, et al. Emerging therapeutics for patients with triple-negative breast cancer[J]. Curr Oncol Rep, 2021, 23(5): 57. doi: 10.1007/s11912-021-01038-6
[30]	KALINSKY K, HONG F X, MCCOURT C K, et al. Effect of capivasertib in patients with an AKT1 E17K-mutated tumor: NCI-MATCH subprotocol EAY131-Y nonrandomized trial[J]. JAMA Oncol, 2021, 7(2): 271-278. doi: 10.1001/jamaoncol.2020.6741
[31]	SCHMID P, ABRAHAM J, CHAN S, et al. Capivasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer: the PAKT trial[J]. J Clin Oncol, 2020, 38(5): 423-433.
[32]	KIM S B, DENT R, IM S A, et al. Ipatasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer (LOTUS): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial[J]. Lancet Oncol, 2017, 18(10): 1360-1372. doi: 10.1016/S1470-2045(17)30450-3
[33]	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. doi: 10.1093/annonc/mdz177
[34]	RICCARDI C, NAPOLITANO E, PLATELLA C, et al. Anti-VEGF DNA-based aptamers in cancer therapeutics and diagnostics[J]. Med Res Rev, 2021, 41(1): 464-506. doi: 10.1002/med.21737
[35]	VON MINCKWITZ G, EIDTMANN H, REZAI M, et al. Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer[J]. N Engl J Med, 2012, 366(4): 299-309. doi: 10.1056/NEJMoa1111065
[36]	SHEPHERD J H, BALLMAN K, POLLEY M C, et al. CALGB 40603 (alliance): long-term outcomes and genomic correlates of response and survival after neoadjuvant chemotherapy with or without carboplatin and bevacizumab in triple-negative breast cancer[J]. J Clin Oncol, 2022, 40(12): 1323-1334. doi: 10.1200/JCO.21.01506
[37]	CAMERON D, BROWN J, DENT R, et al. Adjuvant bevacizumab-containing therapy in triple-negative breast cancer (BEATRICE): primary results of a randomised, phase 3 trial[J]. Lancet Oncol, 2013, 14(10): 933-942. doi: 10.1016/S1470-2045(13)70335-8
[38]	MILLER K D, O’NEILL A, GRADISHAR W, et al. Double-blind phase Ⅲ trial of adjuvant chemotherapy with and without bevacizumab in patients with lymph node-positive and high-risk lymph node-negative breast cancer (E5103)[J]. J Clin Oncol, 2018, 36(25): 2621-2629. doi: 10.1200/JCO.2018.79.2028
[39]	KONO M, FUJII T, LIM B, et al. Androgen receptor function and androgen receptor-targeted therapies in breast cancer: a review[J]. JAMA Oncol, 2017, 3(9): 1266-1273. doi: 10.1001/jamaoncol.2016.4975
[40]	SALVI S, BONAFÈ M, BRAVACCINI S. Androgen receptor in breast cancer: a wolf in sheep’s clothing? A lesson from prostate cancer[J]. Semin Cancer Biol, 2020, 60: 132-137. doi: 10.1016/j.semcancer.2019.04.002
[41]	GUCALP A, TOLANEY S, ISAKOFF S J, et al. Phase Ⅱ trial of bicalutamide in patients with androgen receptor-positive, estrogen receptor-negative metastatic breast cancer[J]. Clin Cancer Res, 2013, 19(19): 5505-5512. doi: 10.1158/1078-0432.CCR-12-3327
[42]	TRAINA T A, MILLER K, YARDLEY D A, et al. Enzalutamide for the treatment of androgen receptor-expressing triple-negative breast cancer[J]. J Clin Oncol, 2018, 36(9): 884-890. doi: 10.1200/JCO.2016.71.3495
[43]	TARANTINO P, CARMAGNANI PESTANA R, CORTI C, et al. Antibody-drug conjugates: smart chemotherapy delivery across tumor histologies[J]. CA Cancer J Clin, 2022, 72(2): 165-182. doi: 10.3322/caac.21705
[44]	INDINI A, RIJAVEC E, GROSSI F. Trastuzumab deruxtecan: changing the destiny of HER2 expressing solid tumors[J]. Int J Mol Sci, 2021, 22(9): 4774. doi: 10.3390/ijms22094774
[45]	CORTÉS J, KIM S B, CHUNG W P, et al. Trastuzumab deruxtecan versus trastuzumab emtansine for breast cancer[J]. N Engl J Med, 2022, 386(12): 1143-1154. doi: 10.1056/NEJMoa2115022
[46]	MODI S N, SAURA C, YAMASHITA T, et al. Trastuzumab deruxtecan in previously treated HER2-positive breast cancer[J]. N Engl J Med, 2020, 382(7): 610-621. doi: 10.1056/NEJMoa1914510
[47]	TARANTINO P, HAMILTON E, TOLANEY S M, et al. HER2-low breast cancer: pathological and clinical landscape[J]. J Clin Oncol, 2020, 38(17): 1951-1962.
[48]	MODI S N, JACOT W, YAMASHITA T, et al. Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer[J]. N Engl J Med, 2022, 387(1): 9-20. doi: 10.1056/NEJMoa2203690
[49]	MAENNLING A E, TUR M K, NIEBERT M, et al. Molecular targeting therapy against EGFR family in breast cancer: progress and future potentials[J]. Cancers (Basel), 2019, 11(12): E1826.
[50]	SHEN M H, JIANG Y Z, WEI Y, et al. Tinagl1 suppresses triple-negative breast cancer progression and metastasis by simultaneously inhibiting integrin/FAK and EGFR signaling[J]. Cancer Cell, 2019, 35(1): 64-80.e7. doi: 10.1016/j.ccell.2018.11.016
[51]	BERNSDORF M, INGVAR C, JÖRGENSEN L, et al. Effect of adding gefitinib to neoadjuvant chemotherapy in estrogen receptor negative early breast cancer in a randomized phase Ⅱ trial[J]. Breast Cancer Res Treat, 2011, 126(2): 463-470. doi: 10.1007/s10549-011-1352-2
[52]	BASELGA J, GÓMEZ P, GREIL R, et al. Randomized phase Ⅱ study of the anti-epidermal growth factor receptor monoclonal antibody cetuximab with cisplatin versus cisplatin alone in patients with metastatic triple-negative breast cancer[J]. J Clin Oncol, 2013, 31(20): 2586-2592. doi: 10.1200/JCO.2012.46.2408
[53]	CAREY L A, RUGO H S, MARCOM P K, et al. TBCRC 001: randomized phase Ⅱ study of cetuximab in combination with carboplatin in stage Ⅳ triple-negative breast cancer[J]. J Clin Oncol, 2012, 30(21): 2615-2623. doi: 10.1200/JCO.2010.34.5579
[54]	LI C J, TZENG Y T, CHIU Y H, et al. Pathogenesis and potential therapeutic targets for triple-negative breast cancer[J]. Cancers (Basel), 2021, 13(12): 2978. doi: 10.3390/cancers13122978
[55]	AGOSTINETTO E, LOSURDO A, NADER-MARTA G, et al. Progress and pitfalls in the use of immunotherapy for patients with triple negative breast cancer[J]. Expert Opin Investig Drugs, 2022, 31(6): 567-591. doi: 10.1080/13543784.2022.2049232
[56]	WU S Y, WANG H, SHAO Z M, et al. Triple-negative breast cancer: new treatment strategies in the era of precision medicine[J]. Sci China Life Sci, 2021, 64(3): 372-388. doi: 10.1007/s11427-020-1714-8
[57]	TARANTINO P, ANTONARELLI G, ASCIONE L, et al. Investigational immunomodulatory drugs for enhancement of triple negative breast cancer (TNBC) immunotherapy: early phase development[J]. Expert Opin Investig Drugs, 2022, 31(6): 499-513. doi: 10.1080/13543784.2021.1972968
[58]	NANDA, CHOW L Q, DEES E C, et al. Pembrolizumab in patients with advanced triple-negative breast cancer: phase Ⅰb KEYNOTE-012 study[J]. J Clin Oncol, 2016, 34(21): 2460-2467. doi: 10.1200/JCO.2015.64.8931
[59]	ADAMS S, SCHMID P, RUGO H S, et al. Pembrolizumab monotherapy for previously treated metastatic triple-negative breast cancer: cohort A of the phase Ⅱ KEYNOTE-086 study[J]. Ann Oncol, 2019, 30(3): 397-404. doi: 10.1093/annonc/mdy517
[60]	ADAMS S, LOI S, TOPPMEYER D, et al. Pembrolizumab monotherapy for previously untreated, PD-L1-positive, metastatic triple-negative breast cancer: cohort B of the phase Ⅱ KEYNOTE-086 study[J]. Ann Oncol, 2019, 30(3): 405-411. doi: 10.1093/annonc/mdy518
[61]	WINER E P, LIPATOV O, IM S A, et al. Pembrolizumab versus investigator-choice chemotherapy for metastatic triple-negative breast cancer (KEYNOTE-119): a randomised, open-label, phase 3 trial[J]. Lancet Oncol, 2021, 22(4): 499-511. doi: 10.1016/S1470-2045(20)30754-3
[62]	CORTES J, CESCON D W, RUGO H S, et al. 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[J]. Lancet, 2020, 396(10265): 1817-1828. doi: 10.1016/S0140-6736(20)32531-9
[63]	CORTÉS J, CESCON D W, RUGO H S, et al. LBA16 KEYNOTE-355: final results from a randomized, double-blind phase Ⅲ study of first-line pembrolizumab + chemotherapy vs placebo + chemotherapy for metastatic TNBC[J]. Ann Oncol, 2021, 32: S1289-S1290.
[64]	HEEKE A L, TAN A R. Checkpoint inhibitor therapy for metastatic triple-negative breast cancer[J]. Cancer Metastasis Rev, 2021, 40(2): 537-547. doi: 10.1007/s10555-021-09972-4
[65]	SCHMID P, SALGADO R, PARK Y H, et al. 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[J]. Ann Oncol, 2020, 31(5): 569-581. doi: 10.1016/j.annonc.2020.01.072
[66]	NANDA, LIU M C, YAU C, 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[J]. JAMA Oncol, 2020, 6(5): 676-684. doi: 10.1001/jamaoncol.2019.6650
[67]	SCHMID P, CORTES J, DENT R, et al. Event-free survival with pembrolizumab in early triple-negative breast cancer[J]. N Engl J Med, 2022, 386(6): 556-567. doi: 10.1056/NEJMoa2112651
[68]	SCHMID P, CORTES J, PUSZTAI L, et al. Pembrolizumab for early triple-negative breast cancer[J]. N Engl J Med, 2020, 382(9): 810-821. doi: 10.1056/NEJMoa1910549
[69]	SCHMID P, RUGO H S, ADAMS S, et al. Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial[J]. Lancet Oncol, 2020, 21(1): 44-59. doi: 10.1016/S1470-2045(19)30689-8
[70]	EMENS L A, ADAMS S, BARRIOS C H, et al. First-line atezolizumab plus nab-paclitaxel for unresectable, locally advanced, or metastatic triple-negative breast cancer: IMpassion130 final overall survival analysis[J]. Ann Oncol, 2021, 32(8): 983-993. doi: 10.1016/j.annonc.2021.05.355
[71]	MILES D, GLIGOROV J, ANDRÉ F, et al. 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[J]. Ann Oncol, 2021, 32(8): 994-1004. doi: 10.1016/j.annonc.2021.05.801
[72]	MITTENDORF E A, ZHANG H, BARRIOS C H, 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. doi: 10.1016/S0140-6736(20)31953-X
[73]	BACHELOT T, FILLERON T, BIECHE I, et al. Durvalumab compared to maintenance chemotherapy in metastatic breast cancer: the randomized phase Ⅱ SAFIR02-BREAST IMMUNO trial[J]. Nat Med, 2021, 27(2): 250-255. doi: 10.1038/s41591-020-01189-2
[74]	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. doi: 10.1093/annonc/mdz158
[75]	TIAN Y G, LI Y L, SHAO Y P, et al. Gene modification strategies for next-generation CAR-T cells against solid cancers[J]. J Hematol Oncol, 2020, 13(1): 54. doi: 10.1186/s13045-020-00890-6
[76]	CAR-T cell therapy shows early potential in TNBC[EB/OL]. 2018, https://www.onclive.com/view/initial-results-of-car-tcell-therapy-study-show-tolerability-in-vivo-expansion-in-tnbc.
[77]	CORTI C, VENETIS K, SAJJADI E, et al. CAR-T cell therapy for triple-negative breast cancer and other solid tumors: preclinical and clinical progress[J]. Expert Opin Investig Drugs, 2022, 31(6): 593-605. doi: 10.1080/13543784.2022.2054326
[78]	SAXENA M, VAN DER BURG S H, MELIEF C J M, et al. Therapeutic cancer vaccines[J]. Nat Rev Cancer, 2021, 21(6): 360-378. doi: 10.1038/s41568-021-00346-0
[79]	ZHU S Y, YU K D. Breast cancer vaccines: disappointing or promising?[J]. Front Immunol, 2022, 13: 828386. doi: 10.3389/fimmu.2022.828386
[80]	MORSE M A, GWIN W R 3rd, MITCHELL D A. Vaccine therapies for cancer: then and now[J]. Target Oncol, 2021, 16(2): 121-152. doi: 10.1007/s11523-020-00788-w
[81]	VINAYAK S, TOLANEY S M, SCHWARTZBERG L, et al. Open-label clinical trial of niraparib combined with pembrolizumab for treatment of advanced or metastatic triple-negative breast cancer[J]. JAMA Oncol, 2019, 5(8): 1132-1140. doi: 10.1001/jamaoncol.2019.1029
[82]	PUSZTAI L, YAU C, WOLF D M, et al. Durvalumab with olaparib and paclitaxel for high-risk HER2-negative stage Ⅱ/Ⅲ breast cancer: results from the adaptively randomized I-SPY2 trial[J]. Cancer Cell, 2021, 39(7): 989-998.e5. doi: 10.1016/j.ccell.2021.05.009
[83]	CHIEN A J, GLIWA A S, RAHMAPUTRI S, et al. A phase Ⅰb trial of the cyclin-dependent kinase inhibitor dinaciclib (dina) in combination with pembrolizumab (P) in patients with advanced triple-negative breast cancer (TNBC) and response correlation with Myc-overexpression[J]. J Clin Oncol, 2020, 38(15_suppl): 1076. doi: 10.1200/JCO.2020.38.15_suppl.1076