Expression of programmed death ligand 1 in patients with triple‑negative breast cancer: Association with clinicopathological parameters

Hasan,Farah Falah; Yahya,Alaa Qasim; Fadhil,Mohammed Haider; Hussain,Ahmad Fawzi

doi:10.3892/wasj.2024.259

Expression of programmed death ligand 1 in patients with triple‑negative breast cancer: Association with clinicopathological parameters

Authors:
- Farah Falah Hasan
- Alaa Qasim Yahya
- Mohammed Haider Fadhil
- Ahmad Fawzi Hussain
View Affiliations

Affiliations: Department of Pathology, Faculty of Medicine, University of Kerbala, Kerbala 56001, Iraq, Department of Pathology and Forensic Medicine, Al‑Kindy College of Medicine, University of Baghdad, Baghdad 10045, Iraq, Department of Plastic Surgery, Gazi Al‑Hariri Teaching Hospital, Baghdad Medical City, Baghdad 10007, Iraq, Department of Gynecology and Obstetrics, Medical Faculty, Justus‑Liebig‑University Giessen, D-35392 Giessen, Germany
Published online on: June 25, 2024 https://doi.org/10.3892/wasj.2024.259
Article Number: 44
Copyright : © Hasan et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The utilization of targeted therapy for programmed death ligand 1 (PD‑L1) has emerged as a prominent focus in contemporary clinical trials, particularly in the context of immune checkpoint inhibitors. The prognostic significance of the expression of PD‑L1 in invasive mammary cancer remains a subject of discussion in clinical oncology, requiring further exploration, despite its recognition as a biomarker for responsiveness to anti‑PDL1 immunotherapy. The present study was conducted to investigate the immunohistological expression of PD‑L1 in women with triple‑negative breast cancer (TNBC), with a particular focus for searching for the associated clinical and pathological characteristics. The present retrospective study examined the immunohistochemical expression of PD‑L1 in 40 formalin‑fixed paraffin‑embedded blocks provided by core needle biopsies from women with TNBC. Data analysis was performed by comparing PDL1 expression with histological grade, the presence or the absence of calcification, the presence or the absence of necrosis and axillary lymph node status at presentation. The positivity of PD‑L1 expression was found in 24 (60%) of the total number of samples. The mean number of PD‑L1 positive samples was 37.8333±21.857. There was a non‑statistically significant association between PD‑L1 positivity, histological grade and the presence of tissue necrosis. A statistically significant association was found between PD‑L1 positivity and the presence of calcification and positive axillary lymph node status at presentation. On the whole, the present study demonstrates that PD‑L1 expression is present at a relatively high prevalence rate in TNBC; thus, it is rational to examine PD‑L1 expression in women with TNBC.

View Figures

View References

1	Dawson AE and Mulford DK: Benign versus malignant papillary neoplasms of the breast. Diagnostic clues in fine-needle aspiration cytology. Acta Cytol. 80:23–28. 1994.PubMed/NCBI
2	Lafta RK: Health System in Iraq Post-2003 War. Al-Kindy Col Med J. 19:5–11. 2023.
3	Sahu N, Agrahari AK, Parida B and Das S: Radiological Significance of Shear-Wave Elastography Technique for Evaluation of Solid Breast Masses with Histopathological Correlation. Al-Kindy Col Med J. 19:26–30. 2023.
4	Aswad N and Abedtwfeq RH: Ultrasound-guided Core Needle Biopsy in the Diagnosis of Suspicious Breast Lesions: Radiologist's Perspectives. Al-Kindy Col Med J. 19:22–29. 2023.
5	Foulkes WD, Smith IE and Reis-Filho JS: Triple-negative breast cancer. N Engl J Med. 363:1938–1948. 2010.PubMed/NCBI View Article : Google Scholar
6	Garrido-Castro AC, Lin NU and Polyak K: Insights into molecular classifications of triple-negative breast cancer: Improving patient selection for treatment. Cancer Discov. 9:176–198. 2019.PubMed/NCBI View Article : Google Scholar
7	Borri F and Granaglia A: Pathology of triple-negative breast cancer. Semin Cancer Biol. 72:136–145. 2021.PubMed/NCBI View Article : Google Scholar
8	Vlajnic T, Baur F, Soysal SD, Weber WP, Piscuoglio S and Muenst S: PD-L1 expression in triple-negative breast cancer: A comparative study of 3 different antibodies. Appl Immunohistochem Mol Morphol. 30:726–730. 2022.PubMed/NCBI View Article : Google Scholar
9	Li CH, Karantza V, Aktan G and Lala M: Current treatment landscape for patients with locally recurrent inoperable or metastatic triple-negative breast cancer: A systematic literature review. Breast Cancer Res. 21(143)2019.PubMed/NCBI View Article : Google Scholar
10	Galluzzi L, Humeau J, Buque A, Zitvogel L and Kroemer G: Immunostimulation with chemotherapy in the era of immune checkpoint inhibitors. Nat Rev Clin Oncol. 17:725–741. 2020.PubMed/NCBI View Article : Google Scholar
11	Yang T, Li W, Huang T and Zhou J: Immunotherapy Targeting PD-1/PD-L1 in Early-stage triple-negative breast cancer. J Pers Med. 13(526)2023.PubMed/NCBI View Article : Google Scholar
12	Denkert C, von Minckwitz G, Darb-Esfahani S, Lederer B, Heppner BI, Weber KE, Budczies J, Huober J, Klauschen F, Furlanetto J, et al: Tumor-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: A pooled analysis of 3771 patients treated with neoadjuvant therapy. Lancet Oncol. 19:40–50. 2018.PubMed/NCBI View Article : Google Scholar
13	Han Y, Liu D and Li L: PD-1/PD-L1 pathway: Current research in cancer. Am J Cancer Res. 10:727–742. 2020.PubMed/NCBI
14	Yarchoan M, Johnson BR III, Lutz ER, Laheru DA and Jaffee EM: Targeting neoantigens to augment antitumor immunity. Nat Rev Cancer. 17:209–222. 2017.
15	Schmid P, Rugo HS, Adams S, Schneeweiss A, Barrios CH, Iwata H, Dieras V, Henschel V, Molinero L, Chui SY, 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 randomized, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 21:44–59. 2020.PubMed/NCBI View Article : Google Scholar
16	Loibl S, Untch M, Burchardi N, Huober J, Sinn BV, Blohmer JU, Grischke EM, Furlanetto J, Tesch H, Hanusch C, 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. Ann Oncol. 30:1279–1288. 2019.PubMed/NCBI View Article : Google Scholar
17	Loibl S, Schneeweiss A, Huober J, Braun M, Rey J, Blohmer JU, Furlanetto J, Zahm DM, Hanusch C, Thomalla J, et al: Neoadjuvant durvalumab improves survival in early triple-negative breast cancer independent of pathological complete response. Ann. Oncol. 33:1149–1158. 2022.PubMed/NCBI View Article : Google Scholar
18	Rizzo A, Cusmai A, Acquafredda S, Giovannelli F, Rinaldi L, Misino A and Palmiotti G: KEYNOTE-522, IMpassion031 and GeparNUEVO: Changing the paradigm of neoadjuvant immune checkpoint inhibitors in early triple-negative breast cancer. Future Oncol. 18:2301–2309. 2022.PubMed/NCBI View Article : Google Scholar
19	Sharpe AH and Pauken KE: The diverse functions of the PD1 inhibitory pathway. Nat Rev Immunol. 18:153–167. 2018.PubMed/NCBI View Article : Google Scholar
20	Ai L, Xu A and Xu J: Roles of the PD-1/PD-L1 Pathway: Signaling, cancer, and beyond. Adv Exp Med Biol. 1248:33–59. 2020.PubMed/NCBI View Article : Google Scholar
21	Jiang X, Wang J, Deng X, Xiong F, Ge J, Xiang B, Wu X, Ma J, Zhou M, Li X, et al: Role of the tumor microenvironment in PD-L1/PD-1-mediated tumor immune escape. Mol Cancer. 18(10)2019.PubMed/NCBI View Article : Google Scholar
22	Badve SS, Penault-Llorca F, Reis-Filho JS, Deurloo R, Siziopikou KP, D'Arrigo C and Viale G: Determining PD-L1 Status in Patients With Triple-Negative Breast Cancer: Lessons Learned From IMpassion 130. J Natl Cancer Inst. 114:664–675. 2022.PubMed/NCBI View Article : Google Scholar
23	Schmid P, Cortes J, Pusztai L, McArthur H, Kümmel S, Bergh J, Denkert C, Park YH, Hui R, Harbeck N, et al: Pembrolizumab for early triple-negative breast cancer. N Engl J Med. 382:810–821. 2020.PubMed/NCBI View Article : Google Scholar
24	Mittendorf EA, Zhang H, Barrios CH, Saji S, Jung KH, Hegg R, Koehler A, Sohn J, Iwata H, Telli ML, 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. Lancet. 396:1090–1100. 2020.PubMed/NCBI View Article : Google Scholar
25	Schmid P, Adams S, Rugo HS, Schneeweiss A, Barrios CH, Iwata H, Diéras V, Hegg R, Im SA, Shaw Wright G, et al: Atezolizumab and Nab-Paclitaxel in Advanced Triple-negative breast cancer. N Engl J Med. 379:2108–2121. 2018.PubMed/NCBI View Article : Google Scholar
26	Keorges GJ: PD-L1 expression in Triple Negative Breast Cancer: A study of an Iraqi population. J Med Sci. 92(e806)2023.
27	Erber R and Hartmann A: Understanding PD-L1 testing in breast cancer: A practical approach. Breast Care (Basel). 15:481–490. 2020.PubMed/NCBI View Article : Google Scholar
28	Marletta S, Fusco N, Munari E, Luchini C, Cimadamore A, Brunelli M, Querzoli G, Martini M, Vigliar E, Colombari R, et al: Atlas of PD-L1 for Pathologists: Indications, scores, diagnostic platforms, and reporting systems. J Pers Med. 12(1073)2022.PubMed/NCBI View Article : Google Scholar
29	Mittendorf EA, Philips AV, Meric-Bernstam F, Qiao N, Wu Y, Harrington S, Su X, Wang Y, Gonzalez-Angulo AM, Akcakanat A, et al: PD-L1 expression in triple-negative breast cancer. Cancer Immunol Res. 2:361–370. 2014.PubMed/NCBI View Article : Google Scholar
30	Beckers RK, Selinger CI, Vilain R, Madore J, Wilmott JS, Harvey K, Holliday A, Cooper CL, Robbins E, Gillett D, et al: Programmed death ligand 1 expression in triple-negative breast cancer is associated with tumor-infiltrating lymphocytes and improved outcome. Histopathology. 69:25–34. 2016.PubMed/NCBI View Article : Google Scholar
31	Oner G, Önder S, Karatay H, Ak N, Tükenmez M, Müslümanoğlu M, İğci A, Dincçağ A, Özmen V, Aydiner A, et al: Clinical impact of PD-L1 expression in triple-negative breast cancer patients with residual tumor burden after neoadjuvant chemotherapy. World J Surg Oncol. 19(264)2021.PubMed/NCBI View Article : Google Scholar
32	Doğukan R, Uçak R, Doğukan FM, Tanık C, Çitgez B and Kabukcuoğlu F: Correlation between the expression of PD-L1 and clinicopathological parameters in triple negative breast cancer patients. Eur J Breast Health. 15:235–241. 2019.PubMed/NCBI View Article : Google Scholar
33	Gonzalez-Ericsson PI, Stovgaard ES, Sua LF, Reisenbichler E, Kos Z, Carter JM, Michiels S, Le Quesne J, Nielsen TO, Laenkholm AV, et al: The path to a better biomarker: Application of a risk management framework for the implementation of PD-L1 and TILs as immuno-oncology biomarkers in breast cancer clinical trials and daily practice. J Pathol. 250:667–684. 2020.PubMed/NCBI View Article : Google Scholar