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. 2015 Mar 10;6(7):5449-64.
doi: 10.18632/oncotarget.3216.

Prognostic and predictive value of PDL1 expression in breast cancer

Renaud Sabatier  1   2   3 , Pascal Finetti  1 , Emilie Mamessier  1 , José Adelaide  1 , Max Chaffanet  1 , Hamid Raza Ali  4   5 , Patrice Viens  1   2   3 , Carlos Caldas  5 , Daniel Birnbaum  1 , François Bertucci  1   2   3
Affiliations

Prognostic and predictive value of PDL1 expression in breast cancer

Renaud Sabatier et al. Oncotarget. .

Abstract

Expression of programmed cell death receptor ligand 1 (PDL1) has been scarcely studied in breast cancer. Recently PD1/PDL1-inhibitors have shown promising results in different carcinomas with correlation between PDL1 tumor expression and responses. We retrospectively analyzed PDL1 mRNA expression in 45 breast cancer cell lines and 5,454 breast cancers profiled using DNA microarrays. Compared to normal breast samples, PDL1 expression was upregulated in 20% of clinical samples and 38% of basal tumors. High expression was associated with poor-prognosis features (large tumor size, high grade, ER-negative, PR-negative, ERBB2-positive status, high proliferation, basal and ERBB2-enriched subtypes). PDL1 upregulation was associated with biological signs of strong cytotoxic local immune response. PDL1 upregulation was not associated with survival in the whole population, but was associated with better metastasis-free and overall specific survivals in basal tumors, independently of clinicopathological features. Pathological complete response after neoadjuvant chemotherapy was higher in case of PDL1 upregulation (50% versus 21%). In conclusion, PDL1 upregulation, more frequent in basal breast cancers, was associated with increased T-cell cytotoxic immune response. In this aggressive subtype, upregulation was associated with better survival and response to chemotherapy. Reactivation of dormant tumor-infiltrating lymphocytes by PDL1-inhibitors could represent promising strategy in PDL1-upregulated basal breast cancer.

Keywords: PDL1; breast cancer; chemotherapy; immune response; survival.

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Conflict of interest statement

Competing interest

The authors have no conflict of interest to declare.

Figures

Figure 1
Figure 1. PD-L1 mRNA expression across molecular subtypes of breast cancer cell lines
PDL1 expression level reported as a box plot according to the molecular subtype of cell lines. The p-values are indicated (Tukey test) are indicated as follows: **, p<0.01; ***, p<0.001; NS, p>0.05.
Figure 2
Figure 2. Metastasis-free survival according to PDL1 mRNA expression in the whole population and in basal breast cancers
A/ Kaplan-Meier MFS curves in patients with high and low expression in the whole population. The 5-year MFS was 61% in both groups. B/ Similar to (A), but limited to patients with basal breast cancer. The respective 5-year MFS were 63 and 44%.
Figure 3
Figure 3. Overall specific survival according to PDL1 mRNA expression in the whole population and in basal breast cancers
A/ Kaplan-Meier OSS curves in patients with high and low expression in the whole population. The respective 5-year OSS were 84 and 82%. B/ Similar to (A), but limited to patients with basal breast cancer. The respective 5-year OSS were 82 and 68%.
See this image and copyright information in PMC

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