Prognostic Role of PD-L1 Expression in Invasive Breast Cancer: A Systematic Review and Meta-Analysis

Cirqueira, Magno Belém; Mendonça, Carolina Rodrigues; Soares, Leonardo Ribeiro; Cysneiros, Maria Auxiliadora de Paula Carneiro; Paulinelli, Régis Resende; Moreira, Marise Amaral Rebouças; Freitas‐Júnior, Ruffo

doi:10.3390/cancers13236090

Cited by 19 publications

(21 citation statements)

References 50 publications

(165 reference statements)

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“…26,27 For instance, HER2-positive status provides prognostic information in node-negative breast cancer and predictive information in selecting targeted and systemic therapy. [28][29][30] One possible explanation from our study was the small number of patients with unfavorable results (n=26), which might limit our statistical power in detecting these associations. Further research with a larger sample size and the number of outcomes is needed.…”

Section: Discussionmentioning

confidence: 92%

Clinicopathological Risk Factors of Unfavorable Outcomes in Vietnamese Women with Primary Invasive Breast Cancer: A Retrospective Cohort Study

Huynh¹,

Huynh²,

Truong³

et al. 2023

BCTT

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Background:The rate of unfavorable outcomes, such as recurrence and death, in women with invasive breast cancer varies widely across countries and populations. Identifying those with high-risk profiles is critical so that early detection, prediction, and intervention can be made to improve their survival rate. Therefore, our study evaluated the rate of unfavorable outcomes and its association with clinicopathological characteristics in Vietnamese women with primary invasive breast cancer. Methods:A retrospective open cohort study was conducted on Vietnamese women with invasive breast cancer who underwent a mastectomy and were regularly followed up by the hospitals. Kaplan-Meier method was used to estimate the rate of unfavorable outcomes to take into account the follow-up time of each patient. Univariate and multiple Cox regression analyses were conducted to examine the associations between unfavorable outcomes and clinicopathological characteristics. Results: Among 204 women included in the data analysis, the mean age was 54.4 ± 10.9 years. The majority of patients were diagnosed with early-stage (76.5%) or locally advanced (22.5%) breast cancer. The 5-year rate of unfavorable outcomes was 12.8%, and the 8-year rate was 31.7%. Patients with advanced stages had a higher risk of unfavorable outcomes compared to those with early stages (IA, IIA, T2N1). Patients with lymph node metastases and those with triple-negative molecular classification had significantly higher rates of unfavorable outcomes. Conclusion: Although Vietnamese women with breast cancer have a relatively low rate of unfavorable outcomes compared to other countries, findings from this study emphasize the importance of early detection and underscore the need for targeted interventions for patients with advanced stages, lymph node metastases, and triple-negative breast cancer to optimize their treatment, outcomes, and overall prognosis.

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Section: Discussionmentioning

confidence: 92%

Clinicopathological Risk Factors of Unfavorable Outcomes in Vietnamese Women with Primary Invasive Breast Cancer: A Retrospective Cohort Study

Huynh¹,

Huynh²,

Truong³

et al. 2023

BCTT

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“…Studies demonstrated that PD-L1 expression varies across different BC subtypes with positivity rates ranging from 0-83% [19,20]. A higher rate of PD-L1 expression has been demonstrated in a subset of BCs with aggressive clinicopathological and immunohistochemical tumor features, such as grade 3 tumors, ER and PR negativity, or Ki-67 proliferation greater than 14%, and this was associated with lower overall survival (OS) [21,22]. A meta-analysis of 19,870 patients revealed a higher rate of PD-L1 expression in breast tumors with a pathological complete response (pCR) following neoadjuvant chemotherapy [21].…”

Section: Of 12mentioning

confidence: 99%

Tumor-Infiltrating Lymphocytes and PD-L1 Expression in Pleomorphic Lobular Breast Carcinoma

Göker¹,

Vijver²,

Denys³

et al. 2023

Preprint

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Background: The prognostic and predictive role of stromal tumor-infiltrating lymphocytes (sTILs) is undetermined in pleomorphic invasive lobular cancer (pILC). The same applies for the expression of PD-1/PD-L1 in this rare breast cancer subtype. Here, we aimed to investigate the expression of sTILs, and analyze the PD-L1 expression levels in pILC. Methods: Archival tissues from sixty-six patients with pILC were collected. The sTIL density was scored as a percentage of tumor area, using the following cut-offs: 0%; <5%; 5-9%; and 10-50%. PD-L1 expression was analyzed using IHC on formalin-fixed, paraffin-embedded tissue sections, using the SP142 and 22C3 antibodies. Results: 82% of the sixty-six patients were hormone receptor-positive; 8% of cases were triple negative (TN), while 10% showed human epidermal growth factor receptor 2 (HER2) amplification. sTILs were present in 64% (1%) of the study population. Using the SP142 antibody, 36% of tumors demonstrated a positive PD-L1 score of 1%, and 28% had a positive PD-L1 score of 1 using the 22C3 antibody. There was no correlation of sTILs or PD-L1 expression with tumor size, tumor grade, nodal status, expression of estrogen receptor (ER) or amplification of HER2. Our data did not show any difference in survival between the three molecular subtypes of pILC with respect to sTILs and PD-L1 expression. Conclusion: This study shows that pILCs show some degree of sTILs and PD-L1 expression, however this was not associated with survival benefit. Additional large trials are needed to understand the immune infiltration in lobular cancer, even more in the pleomorphic subtype.

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“…Its prognosis is very poor, mainly because of its high metastasis incidence and low efficacy of the current management protocols [ 2 , 3 ]. A worse overall survival (OS) in BC patients was associated with positive expression of PD-L1 [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

“…Many tumors can upregulate the expression of PD-L1, inhibiting anti-tumor T-cell responses and avoiding immune surveillance and elimination. Furthermore, it has been found that the expression of PD-L1 is associated with shorter survival and poorer prognosis in many cancers, including BC [ 4 , 14 ]. TNBC is a highly aggressive metastatic cancer with a very high mortality rate [ 2 ], and 50% of these tumors showed a high level of PD-L1 expression [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

PD-1 Independent Role of PD-L1 in Triple-Negative Breast Cancer Progression

Alkaabi

Arafat

Sulaiman

et al. 2023

IJMS

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Triple-negative breast cancer (TNBC) is a type of breast malignancy characterized by a high proliferative rate and metastatic potential leading to treatment failure, relapse, and poor prognosis. Therefore, efforts are continuously being devoted to understanding its biology and identifying new potential targets. Programmed death-ligand 1 (PD-L1) is an immunosuppressive protein that inactivates T cells by binding to the inhibitory receptor programmed death-1 (PD-1). PD-L1 overexpression in cancer cells contributes to immune evasion and, subsequently, poor survival and prognosis in several cancers, including breast cancer. Apart from its inhibitory impact on T cells, this ligand is believed to have an intrinsic role in cancer cells. This study was performed to clarify the PD-1 independent role of PD-L1 in TNBC MDA-MB-231 cells by knocking out the PD-L1 using three designs of CRISPR-Cas9 lentiviral particles. Our study revealed that PD-L1 knockout significantly inhibited MDA-MB-231 cell proliferation and colony formation in vitro and tumor growth in the chick embryo chorioallantoic membrane (CAM) model in vivo. PD-L1 knockout also decreased the migration and invasion of MDA-MB-231 cells in vitro. We have shown that PD-L1 knockout MDA-MB-231 cells have low levels of p-Akt and p-ERK in addition to some of their downstream proteins, c-Fos, c-Myc, p21, survivin, and COX-2. Furthermore, PD-L1 knockout significantly decreased the expression of Snail and RhoA. This study shows the intrinsic role of PD-L1 in TNBC independently of its binding to PD-1 receptors on T cells. It may pave the way for developing novel therapeutic strategies using PD-L1 inhibitors alone and in combination to treat TNBC more effectively.

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Prognostic Role of PD-L1 Expression in Invasive Breast Cancer: A Systematic Review and Meta-Analysis

Cited by 19 publications

References 50 publications

Clinicopathological Risk Factors of Unfavorable Outcomes in Vietnamese Women with Primary Invasive Breast Cancer: A Retrospective Cohort Study

Clinicopathological Risk Factors of Unfavorable Outcomes in Vietnamese Women with Primary Invasive Breast Cancer: A Retrospective Cohort Study

Tumor-Infiltrating Lymphocytes and PD-L1 Expression in Pleomorphic Lobular Breast Carcinoma

PD-1 Independent Role of PD-L1 in Triple-Negative Breast Cancer Progression

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