Prediktívne biomarkery v imunoterapii triple-negatívneho karcinómu prsníka – súčasné poznatky a perspektívy
Authors:
V. Tancoš; A. Blichárová
Authors‘ workplace:
Ústav patológie UPJŠ LF a UNLP, Košice, Slovenská republika
Published in:
Klin Onkol 2023; 36(1): 28-34
Category:
Review
doi:
https://doi.org/10.48095/ccko202328
Overview
Východiská: Imunoterapia s využitím inhibítorov imunitných kontrolných bodov (immune checkpoint inhibitors – ICIs) ohlásila novú éru v liečbe pokročilého triple-negatívneho karcinómu prsníka (TNBC). Avšak v značnej časti pacientov s TNBC je klinický dopad liečby ICIs nepredvídateľný a vhodné biomarkery identifikujúce nádory citlivé na imunoterapiu sú veľmi potrebné. V súčasnosti klinicky najviac relevantné prediktívne biomarkery účinnosti ICIs predstavuje imunohistochemická analýza expresie ligandu 1 programovanej bunkovej smrti (PD-L1), hodnotenie tumor infiltrujúcich lymfocytov (TIL) v nádorovom mikroprostredí (tumor microenvironment – TME) a vyšetrenie nádorovej mutačnej nálože (tumor mutational burden – TMB). Nové biomarkery súvisiace s aktiváciou signálnej dráhy transformačného rastového faktora beta, s receptorom 1 domény diskoidínu a s trombospondínom 1, ako aj mnohé ďalšie celulárne a molekulárne faktory prítomné v TME, predstavujú potenciálne prediktory účinnosti ICIs využiteľné v budúcnosti. Cieľ: V predkladanom prehľadovom článku sumarizujeme súčasné poznatky o regulácii PD-L1 a o prediktívnej hodnote TIL a s nimi súvisiacimi celulárnymi a molekulárnymi komponentmi prítomnými v systéme TME v TNBC. Tiež sa venujeme TMB a novým biomarkerom s potenciálnou úlohou v predikcii účinnosti ICI a pokúsime sa načrtnúť nové terapeutické stratégie.
Klíčová slova:
tumor infiltrujúce lymfocyty – imunoterapia – ligand 1 programovanej bunkovej smrti – triple-negatívny karcinóm prsníka – nádorová mutačná nálož
Sources
1. Navrátil J, Fabian P, Palácová M et al. Triple negative breast cancer. Klin Onkol 2015; 28 (6): 406–415. doi: 10.14735/amko2015405.
2. Kumar P, Aggarwal R. An overview of triple-negative breast cancer. Arch Gynecol Obstet 2016; 293 (2): 247–269. doi: 10.1007/s00404-015-3859-y.
3. Shen M, Pan H, Chen Y et al. A review of current progress in triple-negative breast cancer therapy. Open Med (Wars) 2020; 15 (1): 1143–1149. doi: 10.1515/med-2020-0138.
4. Li X, Yang J, Peng L et al. Triple-negative breast cancer has worse overall survival and cause-specific survival than non-triple-negative breast cancer. Breast Cancer Res Treat 2017; 161 (2): 279–287. doi: 10.1007/s10549-016-4059-6.
5. Chang-Qing Y, Jie L, Shi-Qi Z et al. Recent treatment progress of triple negative breast cancer. Prog Biophys Mol Biol 2020; 151: 40–53. doi: 10.1016/j.pbiomolbio.2019.11.007.
6. Nagini S. Breast cancer: current molecular therapeutic targets and new players. Anticancer Agents Med Chem 2017; 17 (2): 152–163. doi: 10.2174/1871520616666160502122724.
7. Yin L, Duan J-J, Bian X-W et al. Triple-negative breast cancer molecular subtyping and treatment progress. Breast Cancer Res 2020; 22 (1): 61. doi: 10.1186/s13058-020-01296-5.
8. Gu G, Dustin D, Fuqua SA. Targeted therapy for breast cancer and molecular mechanisms of resistance to treatment. Curr Opin Pharmacol 2016; 31: 97–103. doi: 10.1016/j.coph.2016.11.005.
9. Vagia E, Mahalingam D, Cristofanilli M. The landscape of targeted therapies in TNBC. Cancers (Basel) 2020; 12 (4): 916. doi: 10.3390/cancers12040916.
10. Won K, Spruck C. Triple-negative breast cancer therapy: current and future perspectives (Review). Int J Oncol 2020; 57 (6): 1245–1261. doi: 10.3892/ijo.2020.5135.
11. Singh A, Georgy JT, John AO et al. Pathological response and clinical outcomes in operable triple-negative breast cancer with cisplatin added to standard neoadjuvant chemotherapy. Klin Onkol 2021; 34 (1): 49–55. doi: 10.48095/ccko202149.
12. Sochor M, Chlebus P. Antiangiogenic biotherapy and chemotherapy in breast cancer: review of literature and case report. Klin Onkol 2013; 26 (2): 91–98. doi: 10.14735/amko201391.
13. Bianchini G, Balko JM, Mayer IA et al. Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease. Nat Rev Clin Oncol 2016; 13 (11): 674–690. doi: 10.1038/nrclinonc.2016.66.
14. Ohaegbulam KC, Assal A, Lazar-Molnar E et al. Human cancer immunotherapy with antibodies to the PD-1 and PD-L1 pathway. Trends Mol Med 2015; 21 (1): 24–33. doi: 10.1016/j.molmed.2014.10.009.
15. Cha J-H, Chan L-C, Li C-W et al. Mechanisms controlling PD-L1 expression in cancer. Mol Cell 2019; 76 (3): 359–370. doi: 10.1016/j.molcel.2019.09.030.
16. Jiang Y, Chen M, Nie H et al. PD-1 and PD-L1 in cancer immunotherapy: clinical implications and future considerations. Hum Vaccin Immunother 2019; 15 (5): 1111–1122. doi: 10.1080/21645515.2019.1571892.
17. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 2012; 12 (4): 252–264. doi: 10.1038/nrc3239.
18. Zatloukalová P, Pjechová M, Babčanová S et al. The role of PD-1/PD-L1 signaling pathway in antitumor immune response. Klin Onkol 2016; 29 (Suppl 4): 72–77. doi: 10.14735/amko20164S72.
19. Ai L, Xu A, Xu J. Roles of PD-1/PD-L1 pathway: signaling, cancer, and beyond. Adv Exp Med Biol 2020; 1248: 33–59. doi: 10.1007/978-981-15-3266-5_3.
20. Moyers JT, Glitza Oliva IC. Immunotherapy for melanoma. Adv Exp Med Biol 2021; 1342: 81–111. doi: 10.1007/978-3-030-79308-1_3.
21. Herbst RS, Baas P, Kim D-W et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. The Lancet 2016; 387 (10027): 1540–1550. doi: 10.1016/S0140-6736 (15) 01281-7.
22. Koubková L. Immunotherapy of bronchogenic carcinoma and its perspectives. Klin Onkol 2015; 28 (Suppl 4): 77–81. doi: 10.14735/amko20154S77.
23. Cramer JD, Burtness B, Ferris RL. Immunotherapy for head and neck cancer: recent advances and future directions. Oral Oncol 2019; 99: 104460. doi: 10.1016/j.oraloncology.2019.104460.
24. Büchler T. Immunotherapy for bladder cancer. Klin Onkol 2017; 30 (Suppl 3): 6–9. doi: 10.14735/amko20173S6.
25. Shanbhag S, Ambinder RF. Hodgkin lymphoma: a review and update on recent progress: current progress in Hodgkin lymphoma. CA Cancer J Clin 2018; 68 (2): 116–132. doi: 10.3322/caac.21438.
26. Bocanegra A, Blanco E, Fernandez-Hinojal G et al. PD-L1 in systemic immunity: unraveling its contribution to PD-1/PD-L1 blockade immunotherapy. Int J Mol Sci 2020; 21 (16): 5918. doi: 10.3390/ijms21165918.
27. Rugo HS, Loi S, Adams S et al. PD-L1 immunohistochemistry assay comparison in atezolizumab plus nab-paclitaxel-treated advanced triple-negative breast cancer. J Natl Cancer Inst 2021; 113 (12): 1733–1743. doi: 10.1093/jnci/djab108.
28. Zhao J, Huang J. Breast cancer immunology and immunotherapy: targeting the programmed cell death protein-1/programmed cell death protein ligand-1. Chin Med J (Engl) 2020; 133 (7): 853–862. doi: 10.1097/CM9.0000000000000710.
29. Bai X, Ni J, Beretov J et al. Immunotherapy for triple-negative breast cancer: a molecular insight into the microenvironment, treatment, and resistance. J Natl Cancer Center 2021; 1 (3): 75–87. doi: 10.1016/j.jncc.2021.06.001.
30. Imanishi S, Morishima H, Oda N et al. Significance of PDL1 positive in TNBC. JCO 2020; 38 (Suppl 15): e12557–e12557. doi: 10.1200/JCO.2020.38.15_suppl.e12557.
31. Kolečková M, Kolář Z, Ehrmann J et al. Tumor-infiltrating lymphocytes/plasmocytes in chemotherapeutically non-influenced triple-negative breast cancers – correlation with morphological and clinico-pathological parameters. Klin Onkol 2019; 32 (5): 380–387. doi: 10.14735/amko2019380.
32. Kim I, Sanchez K, McArthur HL et al. Immunotherapy in triple-negative breast cancer: present and future. Curr Breast Cancer Rep 2019; 11: 259–271. doi: 10.1007/s12609-019-00345-z.
33. O’Meara TA, Tolaney SM. Tumor mutational burden as a predictor of immunotherapy response in breast cancer. Oncotarget 2021; 12 (5): 394–400. doi: 10.18632/oncotarget.27877.
34. Cocco S, Piezzo M, Calabrese A et al. Biomarkers in triple-negative breast cancer: state-of-the-art and future perspectives. Int J Mol Sci 2020; 21 (13): 4579. doi: 10.3390/ijms21134579.
35. Adams S, Diamond JR, Hamilton E et al. Atezolizumab plus nab-paclitaxel in the treatment of metastatic triple-negative breast cancer with 2-year survival follow-up: a phase 1b clinical trial. JAMA Oncol 2019; 5 (3): 334. doi: 10.1001/jamaoncol.2018.5152.
36. Emens LA, Cruz C, Eder JP et al. Long-term clinical outcomes and biomarker analyses of atezolizumab therapy for patients with metastatic triple-negative breast cancer: a phase 1 study. JAMA Oncol 2019; 5 (1): 74. doi: 10.1001/jamaoncol.2018.4224.
37. Schmid P, Adams S, Rugo HS et al. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med 2018; 379 (8): 2108–2121. doi: 10.1056/NEJM oa1809615.
38. 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. Ann Oncol 2021; 32 (8): 994–1004. doi: 10.1016/j.annonc.2021.05.801.
39. 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. doi: 10.1016/j.annonc.2021.05.355.
40. Jia H, Truica CI, Wang B et al. Immunotherapy for triple-negative breast cancer: existing challenges and exciting prospects. Drug Resist Updat 2017; 32: 1–15. doi: 10.1016/j.drup.2017.07.002.
41. de Melo Gagliato D, Buzaid AC, Perez-Garcia J et al. Immunotherapy in breast cancer: current practice and clinical challenges. BioDrugs 2020; 34 (5): 611–623. doi: 10.1007/s40259-020-00436-9.
42. Mittendorf EA, Philips AV, Meric-Bernstam F et al. PD-L1 expression in triple-negative breast cancer. Cancer Immunol Res 2014; 2 (4): 361–370. doi: 10.1158/2326-6066.CIR-13-0127.
43. Matikas A, Zerdes I, Lövrot J et al. Prognostic implications of PD-L1 expression in breast cancer: systematic review and meta-analysis of immunohistochemistry and pooled analysis of transcriptomic data. Clin Cancer Res 2019; 25 (18): 5717–5726. doi: 10.1158/1078-0432.CCR-19-1131.
44. Tsang JYS, Au W-L, Lo K-Y et al. PD-L1 expression and tumor infiltrating PD-1+ lymphocytes associated with outcome in HER2+ breast cancer patients. Breast Cancer Res Treat 2017; 162 (1): 19–30. doi: 10.1007/s10549-016-4095-2.
45. Lagos GG, Izar B, Rizvi NA. Beyond tumor PD-L1: emerging genomic biomarkers for checkpoint inhibitor immunotherapy. Am Soc Clin Oncol Educ Book 2020; 40: 1–11. doi: 10.1200/EDBK_289967.
46. Althammer S, Tan TH, Spitzmüller A et al. Automated image analysis of NSCLC biopsies to predict response to anti-PD-L1 therapy. J Immunother Cancer 2019; 7 (1): 121. doi: 10.1186/s40425-019-0589-x.
47. Troncone G, Gridelli C. The reproducibility of PD-L1 scoring in lung cancer: can the pathologists do better? Transl Lung Cancer Res 2017; 6 (Suppl 1): S74–S77. doi: 10.21037/tlcr.2017.10.05.
48. Cottrell TR, Taube JM. PD-L1 and emerging biomarkers in immune checkpoint blockade therapy. Cancer J 2018; 24 (1): 41–46. doi: 10.1097/PPO.0000000000000301.
49. Reddy SM, Carroll E, Nanda R. Atezolizumab for the treatment of breast cancer. Expert Rev Anticancer Ther 2020; 20 (3): 151–158. doi: 10.1080/14737140.2020.1732211.
50. Kwapisz D. Pembrolizumab and atezolizumab in triple-negative breast cancer. Cancer Immunol Immunother 2021; 70 (3): 607–617. doi: 10.1007/s00262-020-02736-z.
51. Pérez-García J, Soberino J, Racca F et al. Atezolizumab in the treatment of metastatic triple-negative breast cancer. Expert Opin Biol Ther 2020; 20 (9): 981–989. doi: 10.1080/14712598.2020.1769063.
52. Schmid P, Salgado R, Park YH 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. Ann Oncol 2020; 31 (5): 569–581. doi: 10.1016/j.annonc.2020.01.072.
53. Lee SE, Park HY, Lim SD et al. Concordance of programmed death-ligand 1 expression between SP142 and 22C3/SP263 assays in triple-negative breast cancer. J Breast Cancer 2020; 23 (3): 303. doi: 10.4048/jbc.2020.23.e37.
54. Wei Y, Zhao Q, Gao Z et al. The local immune landscape determines tumor PD-L1 heterogeneity and sensitivity to therapy. J Clin Invest 2019; 129 (8): 3347–3360. doi: 10.1172/JCI127726.
55. McLaughlin J, Han G, Schalper KA et al. Quantitative assessment of the heterogeneity of PD-L1 expression in non-small-cell lung cancer. JAMA Oncol 2016; 2 (1): 46–54. doi: 10.1001/jamaoncol.2015.3638.
56. Naso JR, Wang G, Pender A et al. Intratumoral heterogeneity in programmed death-ligand 1 immunoreactivity is associated with variation in non-small cell lung carcinoma histotype. Histopathology 2020; 76 (3): 394–403. doi: 10.1111/his.13983.
57. da Silva JL, Cardoso Nunes NC, Izetti P et al. Triple negative breast cancer: a thorough review of biomarkers. Crit Rev Oncol Hematol 2020; 145: 102855. doi: 10.1016/j.critrevonc.2019.102855.
58. Deng J, Thennavan A, Shah S et al. Serial single-cell profiling analysis of metastatic TNBC during Nab-paclitaxel and pembrolizumab treatment. Breast Cancer Res Treat 2021; 185 (1): 85–94. doi: 10.1007/s10549-020-05936-4.
59. Manson QF, Schrijver WAME, ter Hoeve ND et al. Frequent discordance in PD-1 and PD-L1 expression between primary breast tumors and their matched distant metastases. Clin Exp Metastasis 2019; 36 (1): 29–37. doi: 10.1007/s10585-018-9950-6.
60. Sanchez K, Kim I, Chun et al. Multiplex immunofluorescence to measure dynamic changes in tumor-infiltrating lymphocytes and PD-L1 in early-stage breast cancer. Breast Cancer Res 2021; 23 (1): 2. doi: 10.1186/s13058-020-01378-4.
61. Grandal B, Mangiardi-Veltin M, Laas E et al. PD-L1 expression after neoadjuvant chemotherapy in triple-negative breast cancers is associated with aggressive residual disease, suggesting a potential for immunotherapy. Cancers (Basel) 2021; 13 (4): 746. doi: 10.3390/cancers13040746.
62. Deng L, Liang H, Burnette B et al. Irradiation and anti-PD-L1 treatment synergistically promote antitumor immunity in mice. J Clin Invest 2014; 124 (2): 687–695. doi: 10.1172/JCI67313.
63. Patel SP, Kurzrock R. PD-L1 expression as a predictive biomarker in cancer immunotherapy. Mol Cancer Ther 2015; 14 (4): 847–856. doi: 10.1158/1535-7163.MCT-14-0983.
64. Paver EC, Cooper WA, Colebatch AJ et al. Programmed death ligand-1 (PD-L1) as a predictive marker for immunotherapy in solid tumours: a guide to immunohistochemistry implementation and interpretation. Pathology 2021; 53 (2): 141–156. doi: 10.1016/j.pathol.2020.10.007.
65. Lotfinejad P, Asghari Jafarabadi M, Abdoli Shadbad M et al. Prognostic role and clinical significance of tumor--infiltrating lymphocyte (TIL) and programmed death ligand 1 (PD-L1) expression in triple-negative breast cancer (TNBC): a systematic review and meta-analysis study. Diagnostics (Basel) 2020; 10 (9): 704. doi: 10.3390/diagnostics10090704.
66. Labani-Motlagh A, Ashja-Mahdavi M, Loskog A. The tumor microenvironment: a milieu hindering and obstructing antitumor immune responses. Front Immunol 2020; 11: 940. doi: 10.3389/fimmu.2020.00940.
67. Oshi M, Asaoka M, Tokumaru Y et al. CD8 T cell score as a prognostic biomarker for triple negative breast cancer. Int J Mol Sci 2020; 21 (18): 6968. doi: 10.3390/ijms21186968.
68. Paijens ST, Vledder A, de Bruyn M et al. Tumor-infiltrating lymphocytes in the immunotherapy era. Cell Mol Immunol 2021; 18 (4): 842–859. doi: 10.1038/s41423-020-00565-9.
69. Tancoš V, Grendár M, Farkašová A et al. Programmed death-ligand 1 expression in non-small cell lung carcinoma biopsies and its association with tumor infiltrating lymphocytes and the degree of desmoplasia. Klin Onkol 2020; 33 (1): 55–65. doi: 10.14735/amko202055.
70. Salgado R, Denkert C, Demaria S et al. The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014. Ann Oncol 2015; 26 (2): 259–271. doi: 10.1093/annonc/mdu450.
71. Gao G, Wang Z, Qu X et al. Prognostic value of tumor-infiltrating lymphocytes in patients with triple-negative breast cancer: a systematic review and meta-analysis. BMC Cancer 2020; 20 (1): 179. doi: 10.1186/s12885-020-6668-z.
72. 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. Lancet Oncol 2018; 19 (1): 40–50. doi: 10.1016/S1470-2045 (17) 30 904-X.
73. Adams S, Goldstein LJ, Sparano JA et al. Tumor infiltrating lymphocytes (TILs) improve prognosis in patients with triple negative breast cancer (TNBC). Oncoimmunology 2015; 4 (9): e985930. doi: 10.4161/2162402X.2014.985930.
74. Luen SJ, Salgado R, Dieci MV et al. Prognostic implications of residual disease tumor-infiltrating lymphocytes and residual cancer burden in triple-negative breast cancer patients after neoadjuvant chemotherapy. Ann Oncol 2019; 30 (2): 236–242. doi: 10.1093/annonc/mdy547.
75. Gonzalez-Ericsson PI, Stovgaard ES, Sua LF et al. The path to a better biomarker: application of a risk management framework for the implementation of PD-L1 and TILs as immune-oncology biomarkers in breast cancer clinical trials and daily practice. J Pathol 2020; 250 (5): 667–684. doi: 10.1002/path.5406.
76. Yi M, Jiao D, Xu H et al. Biomarkers for predicting efficacy of PD-1/PD-L1 inhibitors. Mol Cancer 2018; 17 (1): 129. doi: 10.1186/s12943-018-0864-3.
77. Yi M, Niu M, Xu L et al. Regulation of PD-L1 expression in the tumor microenvironment. J Hematol Oncol 2021; 14 (1): 10. doi: 10.1186/s13045-020-01027-5.
78. Liu F, Lang R, Zhao J et al. CD8+ cytotoxic T cell and FOXP3+ regulatory T cell infiltration in relation to breast cancer survival and molecular subtypes. Breast Cancer Res Treat 2011; 130 (2): 645–655. doi: 10.1007/s10549-011-1647-3.
79. Liu T, Han C, Wang S et al. Cancer-associated fibroblasts: an emerging target of anti-cancer immunotherapy. J Hematol Oncol 2019; 12 (1): 86. doi: 10.1186/s13045-019-0770-1.
80. Mariathasan S, Turley SJ, Nickles D et al. TGFb attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells. Nature 2018; 554 (7693): 544–548. doi: 10.1038/nature25501.
81. David JM, Dominguez C, McCampbell KK et al. A novel bifunctional anti-PD-L1/TGF-b Trap fusion protein (M7824) efficiently reverts mesenchymalization of human lung cancer cells. Oncoimmunology 2017; 6 (10): e1349589. doi: 10.1080/2162402X.2017.1349 589.
82. Vogel WF, Aszódi A, Alves F et al. Discoidin domain receptor 1 tyrosine kinase has an essential role in mammary gland development. Mol Cell Biol 2001; 21 (8): 2906–2917. doi: 10.1128/MCB.21.8.2906-2917.2001.
83. Sun X, Wu B, Chiang H-C et al. Tumour DDR1 promotes collagen fibre alignment to instigate immune exclusion. Nature 2021; 599 (7886): 673–678. doi: 10.1038/s41586-021-04057-2.
84. Marcheteau E, Farge T, Pérès M et al. Thrombospondin-1 silencing improves lymphocyte infiltration in tumors and response to anti-PD-1 in triple-negative breast cancer. Cancers (Basel) 2021; 13 (16): 4059. doi: 10.3390/cancers13164059.
85. Gao C, Li H, Liu C et al. Tumor mutation burden and immune invasion characteristics in triple negative breast cancer: genome high-throughput data analysis. Front Immunol 2021; 12: 650491. doi: 10.3389/fimmu.2021.650491.
86. Le DT, Uram JN, Wang H et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med 2015; 372 (26): 2509–2520. doi: 10.1056/NEJMoa1500596.
87. Marra A, Viale G, Curigliano G. Recent advances in triple negative breast cancer: the immunotherapy era. BMC Med 2019; 17 (1): 90. doi: 10.1186/s12916-019-1326-5.
88. Barroso-Sousa R, Jain E, Cohen O et al. Prevalence and mutational determinants of high tumor mutation burden in breast cancer. Ann Oncol 2020; 31 (3): 387–394. doi: 10.1016/j.annonc.2019.11.010.
89. Sukumar J, Gast K, Quiroga D et al. Triple-negative breast cancer: promising prognostic biomarkers currently in development. Expert Rev Anticancer Ther 2021; 21 (2): 135–148. doi: 10.1080/14737140.2021.1840984.
90. Goodman AM, Kato S, Bazhenova L et al. Tumor mutational burden as an independent predictor of response to immunotherapy in diverse cancers. Mol Cancer Ther 2017; 16 (11): 2598–2608. doi: 10.1158/1535-7163.MCT-17-0386.
91. Thomas R, Al-Khadairi G, Decock J. Immune checkpoint inhibitors in triple negative breast cancer treatment: promising future prospects. Front Oncol 2021; 10: 600573. doi: 10.3389/fonc.2020.600573.
92. Barroso-Sousa R, Jain E, Cohen O. Prevalence and mutational determinants of high tumor mutation burden in breast cancer. Ann Oncol 2020; 31 (3): 387–394. doi: 10.1016/j.annonc.2019.11.010.
93. Karn T, Denkert C, Weber KE et al. Tumor mutational burden and immune infiltration as independent predictors of response to neoadjuvant immune checkpoint inhibition in early TNBC in GeparNuevo. Ann Oncol 2020; 31 (9): 1216–1222. doi: 10.1016/j.annonc.2020.05.015.
94. Winer EP, Lipatov O, Im S-A et al. Association of tumor mutational burden (TMB) and clinical outcomes with pembrolizumab (pembro) versus chemotherapy (chemo) in patients with metastatic triple-negative breast cancer (mTNBC) from KEYNOTE-119. J Clin Oncol 2020; 38 (Suppl 15): 1013–1013. doi: 10.1200/JCO.2020.38.15_suppl.1013.
Labels
Paediatric clinical oncology Surgery Clinical oncologyArticle was published in
Clinical Oncology
2023 Issue 1
Most read in this issue
- Oncolytic viruses and cancer treatment
- Predictive biomarkers of response to immunotherapy in triple-negative breast cancer – state of the art and future perspectives
- Radiation induced lymphopenia – a possible critical factor in current oncological treatment
- Predictors of cognitive failures in cancer survivors