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Current Cancer Therapy Reviews

Author(s): Mohsen Naghizadeh, Hedieh Moradi Tabriz, Adel Yazdankhah Kenari and Ehsan Khalili*

DOI: 10.2174/1573394718666220331092912

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PDL1 Positivity Rate Between Triple-negative and Non-luminal Her2+ Cases

Page: [215 - 221] Pages: 7

  • * (Excluding Mailing and Handling)

Abstract

Background: Triple-negative breast cancer cases with no available targeted therapy and advanced cases of luminal and HER2+ that become resistant to available state-of-the-art treatments are priorities in cancer research. Immune checkpoint blockade, particularly PDL1/PD1 inhibition, is suggested as a potential option for these patients suffering from several other types of cancers, such as melanoma. However, the exact subpopulation of breast cancer patients that overexpress PDL1 is yet to be completely identified. Additionally, reports on the value of PDL1 as a biomarker for the prognosis of cancer and its correlation with clinicopathological features of malignancy are diverse.

Methods: In this study, we performed immunohistochemistry on 60 breast cancer, including 22 triple-negative and 38 HER2+ cases, and 20 paired lymph node samples.

Results: PDL1 expression was present in 21. 6% (13/60) of breast cancer samples. PDL1 expression is significantly associated with ER/PR negativity and the grade of the tumor. The association between PDL1 positivity and recurrence and the overall survival of patients was not significant.

Conclusion: PDL1 expression is similar between triple-negative and non-luminal HER2+ cases, thus some of the advanced non-luminal HER2+ cases might be benefitted from immune checkpoint blockade.

Keywords: Breast cancer, triple-negative, PDL1, HER2-positive, immunohistochemistry, tumer.

Graphical Abstract

[1]
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin 2019; 69(1): 7-34.
[http://dx.doi.org/10.3322/caac.21551] [PMID: 30620402]
[2]
Hudis CA, Gianni L. Triple-negative breast cancer: An unmet medical need. Oncologist 2011; 16 (Suppl. 1): 1-11.
[http://dx.doi.org/10.1634/theoncologist.2011-S1-01] [PMID: 21278435]
[3]
Hodi FS, O’Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 2010; 363(8): 711-23.
[http://dx.doi.org/10.1056/NEJMoa1003466] [PMID: 20525992]
[4]
Powles T, Eder JP, Fine GD, et al. MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature 2014; 515(7528): 558-62.
[http://dx.doi.org/10.1038/nature13904] [PMID: 25428503]
[5]
Reck M, Rodríguez-Abreu D, Robinson AG, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med 2016; 375(19): 1823-33.
[http://dx.doi.org/10.1056/NEJMoa1606774] [PMID: 27718847]
[6]
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. Lancet 2016; 387(10027): 1540-50.
[http://dx.doi.org/10.1016/S0140-6736(15)01281-7] [PMID: 26712084]
[7]
Mahoney KM, Freeman GJ, McDermott DF. The next immune-checkpoint inhibitors: PD-1/PD-L1 blockade in melanoma. Clin Ther 2015; 37(4): 764-82.
[http://dx.doi.org/10.1016/j.clinthera.2015.02.018] [PMID: 25823918]
[8]
Goldhirsch A, Winer EP, Coates AS, et al. Personalizing the treatment of women with early breast cancer: Highlights of the St Gallen international expert consensus on the primary therapy of early breast cancer 2013. Ann Oncol 2013; 24(9): 2206-23.
[http://dx.doi.org/10.1093/annonc/mdt303] [PMID: 23917950]
[9]
Coates AS, Winer EP, Goldhirsch A, et al. Tailoring therapies--improving the management of early breast cancer: St Gallen international expert consensus on the primary therapy of early breast cancer 2015. Ann Oncol 2015; 26(8): 1533-46.
[http://dx.doi.org/10.1093/annonc/mdv221] [PMID: 25939896]
[10]
Waks AG, Winer EP. Breast cancer treatment: A review. JAMA 2019; 321(3): 288-300.
[http://dx.doi.org/10.1001/jama.2018.19323] [PMID: 30667505]
[11]
Mittendorf EA, Philips AV, Meric-Bernstam F, et al. PD-L1 expression in triple-negative breast cancer. Cancer Immunol Res 2014; 2(4): 361-70.
[http://dx.doi.org/10.1158/2326-6066.CIR-13-0127] [PMID: 24764583]
[12]
Soliman H, Khalil F, Antonia S. PD-L1 expression is increased in a subset of basal type breast cancer cells. PLoS One 2014; 9(2): e88557.
[http://dx.doi.org/10.1371/journal.pone.0088557] [PMID: 24551119]
[13]
Freeman GJ, Long AJ, Iwai Y, et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med 2000; 192(7): 1027-34.
[http://dx.doi.org/10.1084/jem.192.7.1027] [PMID: 11015443]
[14]
Dong H, Strome SE, Salomao DR, et al. Tumor-associated B7-H1 promotes T-cell apoptosis: A potential mechanism of immune evasion. Nat Med 2002; 8(8): 793-800.
[http://dx.doi.org/10.1038/nm730] [PMID: 12091876]
[15]
Iwai Y, Ishida M, Tanaka Y, Okazaki T, Honjo T, Minato N. Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc Natl Acad Sci USA 2002; 99(19): 12293-7.
[http://dx.doi.org/10.1073/pnas.192461099] [PMID: 12218188]
[16]
Seo S-K, Seo H-M, Jeong H-Y, et al. Co-inhibitory role of T-cell-associated B7-H1 and B7-DC in the T-cell immune response. Immunol Lett 2006; 102(2): 222-8.
[http://dx.doi.org/10.1016/j.imlet.2005.09.007] [PMID: 16236366]
[17]
Schmid P, Chui SY, Emens LA. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer Reply. N Engl J Med 2019; 380(10): 987-8.
[PMID: 30855757]
[18]
Nanda R, Chow LQ, Dees EC, et al. Pembrolizumab in patients with advanced triple-negative breast cancer: Phase Ib KEYNOTE-012 study. J Clin Oncol 2016; 34(21): 2460-7.
[http://dx.doi.org/10.1200/JCO.2015.64.8931] [PMID: 27138582]
[19]
Swoboda A, Nanda R. Immune checkpoint blockade for breast cancer. In: Gradishar WJ, Ed. Optimizing Breast Cancer Management. Cham: Springer 2018; pp. 155-65.
[http://dx.doi.org/10.1007/978-3-319-70197-4_10]
[20]
He J, Hu Y, Hu M, Li B. Development of PD-1/PD-L1 pathway in tumor immune microenvironment and treatment for non-small cell lung cancer. Sci Rep 2015; 5(1): 13110.
[http://dx.doi.org/10.1038/srep13110] [PMID: 26279307]
[21]
Zhang M, Sun H, Zhao S, et al. Expression of PD-L1 and prognosis in breast cancer: A meta-analysis. Oncotarget 2017; 8(19): 31347-54.
[http://dx.doi.org/10.18632/oncotarget.15532] [PMID: 28430626]
[22]
Yuan C, Liu Z, Yu Q, et al. Expression of PD-1/PD-L1 in primary breast tumours and metastatic axillary lymph nodes and its correlation with clinicopathological parameters. Sci Rep 2019; 9(1): 14356.
[http://dx.doi.org/10.1038/s41598-019-50898-3] [PMID: 31591439]
[23]
Baptista MZ, Sarian LO, Derchain SF, Pinto GA, Vassallo J. Prognostic significance of PD-L1 and PD-L2 in breast cancer. Hum Pathol 2016; 47(1): 78-84.
[http://dx.doi.org/10.1016/j.humpath.2015.09.006] [PMID: 26541326]
[24]
Polónia A, Pinto R, Cameselle-Teijeiro JF, Schmitt FC, Paredes J. Prognostic value of stromal tumour infiltrating lymphocytes and programmed cell death-ligand 1 expression in breast cancer. J Clin Pathol 2017; 70(10): 860-7.
[http://dx.doi.org/10.1136/jclinpath-2016-203990] [PMID: 28373294]
[25]
Tawfik O, Kimler BF, Karnik T, Shehata P. Clinicopathological correlation of PD-L1 expression in primary and metastatic breast cancer and infiltrating immune cells. Hum Pathol 2018; 80: 170-8.
[http://dx.doi.org/10.1016/j.humpath.2018.06.008] [PMID: 29936058]
[26]
Kurozumi S, Inoue K, Matsumoto H, et al. Clinicopathological values of PD-L1 expression in HER2-positive breast cancer. Sci Rep 2019; 9(1): 16662.
[http://dx.doi.org/10.1038/s41598-019-52944-6] [PMID: 31723167]
[27]
Tsang JY, 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.
[http://dx.doi.org/10.1007/s10549-016-4095-2] [PMID: 28058578]
[28]
Muenst S, Schaerli AR, Gao F, et al. Expression of programmed death ligand 1 (PD-L1) is associated with poor prognosis in human breast cancer. Breast Cancer Res Treat 2014; 146(1): 15-24.
[http://dx.doi.org/10.1007/s10549-014-2988-5] [PMID: 24842267]
[29]
Guan J, Lim KS, Mekhail T, Chang C-C. Programmed death ligand-1 (PD-L1) expression in the programmed death receptor-1 (PD-1)/PD-L1 blockade: A key player against various cancers. Arch Pathol Lab Med 2017; 141(6): 851-61.
[http://dx.doi.org/10.5858/arpa.2016-0361-RA] [PMID: 28418281]
[30]
Sabatier R, Finetti P, Mamessier E, et al. Prognostic and predictive value of PDL1 expression in breast cancer. Oncotarget 2015; 6(7): 5449-64.
[http://dx.doi.org/10.18632/oncotarget.3216] [PMID: 25669979]
[31]
Dill EA, Gru AA, Atkins KA, et al. PD-L1 expression and intratumoral heterogeneity across breast cancer subtypes and stages. Am J Surg Pathol 2017; 41(3): 334-42.
[http://dx.doi.org/10.1097/PAS.0000000000000780] [PMID: 28195880]
[32]
Doğukan R, Uçak R, Doğukan FM, Tanık C, Çitgez B, Kabukcuoğlu F. Correlation between the expression of PD-L1 and clinicopathological parameters in triple negative breast cancer patients. Eur J Breast Health 2019; 15(4): 235-41.
[http://dx.doi.org/10.5152/ejbh.2019.4912] [PMID: 31620682]
[33]
Sun WY, Lee YK, Koo JS. Expression of PD-L1 in triple-negative breast cancer based on different immunohistochemical antibodies. J Transl Med 2016; 14(1): 173.
[http://dx.doi.org/10.1186/s12967-016-0925-6] [PMID: 27286842]
[34]
Park IH, Kong S-Y, Ro JY, et al. Prognostic implications of tumor-infiltrating lymphocytes in association with programmed death ligand 1 expression in early-stage breast cancer. Clin Breast Cancer 2016; 16(1): 51-8.
[http://dx.doi.org/10.1016/j.clbc.2015.07.006] [PMID: 26364145]
[35]
Postow MA, Callahan MK, Wolchok JD. Immune checkpoint blockade in cancer therapy. J Clin Oncol 2015; 33(17): 1974-82.
[http://dx.doi.org/10.1200/JCO.2014.59.4358] [PMID: 25605845]
[36]
Schalper KA, Velcheti V, Carvajal D, et al. In situ tumor PD-L1 mRNA expression is associated with increased TILs and better outcome in breast carcinomas. Clin Cancer Res 2014; 20(10): 2773-82.
[http://dx.doi.org/10.1158/1078-0432.CCR-13-2702] [PMID: 24647569]
[37]
Spranger S, Spaapen RM, Zha Y, et al. Up-regulation of PD-L1, IDO, and T(regs) in the melanoma tumor microenvironment is driven by CD8(+) T cells. Sci Transl Med 2013; 5(200): 200ra116.
[http://dx.doi.org/10.1126/scitranslmed.3006504] [PMID: 23986400]
[38]
Kinter AL, Godbout EJ, McNally JP, et al. The common γ-chain cytokines IL-2, IL-7, IL-15, and IL-21 induce the expression of programmed death-1 and its ligands. J Immunol 2008; 181(10): 6738-46.
[http://dx.doi.org/10.4049/jimmunol.181.10.6738] [PMID: 18981091]