Programmed cell death 1 (PD-1) receptor and programmed death ligand 1 (PD-L1) expression in primary breast cancer (BC); correlations with clinical characteristics and patient outcomes.

Authors

null

Neelima Vidula

UC San Francisco, San Francisco, CA

Neelima Vidula , Christina Yau , Andrei Goga , Hope S. Rugo

Organizations

UC San Francisco, San Francisco, CA, Buck Institute for Age Research, Novato, CA, UC San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, University of California, San Francisco, San Francisco, CA

Research Funding

No funding sources reported

Background: The interaction of the PD-1 receptor on tumor infiltrating lymphocytes and PD-L1 on tumor cells dampens antitumor immunity. Two phase I trials suggested efficacy of anti-PD-1/PD-L1 antibodies in triple negative (TN) BC. This study investigated associations between primary BC PD-1 and PD-L1 expression, clinical characteristics, and patient outcomes in publically available databases. Methods: We evaluated PD-1 and PD-L1 expression using microarray data from the neoadjuvant I-SPY 1 study (n = 149). Associations with clinical features and chemotherapy response were assessed by Kruskal-Wallis and Wilcoxon rank sum tests, respectively. Recurrence free survival (RFS) associations were assessed by the Cox proportional hazard model. Pearson correlations between PD-1 and expression of PD-L1, HAVCR2, STAT5A, FOXP3, MYC, and ESR1 were determined in I-SPY 1 and 2 other datasets: METABRIC (n = 1992) and TCGA (n = 817). Results: In I-SPY 1, PD-1 expression was significantly higher in HER2+ and TNBC (p = 0.003), and in grade 2/3 tumors (p = 0.043); this association was also seen in METABRIC. PD-1 expression was associated with pathologic complete response (p = 0.006) but not with tumor stage, nodal status, lymphovascular invasion or RFS. While PD-L1 did not correlate with tumor features, patients with PD-L1 expression in the lowest quintile had worse RFS, even after subtype adjustment (HR 2.33, p = 0.01). In all 3 datasets, PD-1 significantly correlated with PD-L1, HAVCR2, and STAT5A, and inversely with ESR1. In the TN subset of TCGA and METABRIC, PD-1 significantly correlated with PD-L1, HAVCR2, and STAT5A. In TCGA and METABRIC, PD-L1 significantly correlated with HAVCR2 and STAT5A, and this was also seen in the TN subset. In TCGA alone, PD-1 and PD-L1 significantly correlated with FOXP3, and PD-1 with MYC. Conclusions: PD-1 expression is higher in TN and other aggressive BC subtypes. PD-1 and PD-L1 correlate with immune related genes HAVCR2 and STAT5A. Low PD-L1 expression may be an adverse prognostic factor. Trials are underway to investigate the activity of anti-PD-1/PD-L1 antibodies in TNBC and to elucidate markers of response.

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Abstract Details

Meeting

2015 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Breast Cancer—Triple-Negative/Cytotoxics/Local Therapy

Track

Breast Cancer

Sub Track

Triple-Negative Breast Cancer

Citation

J Clin Oncol 33, 2015 (suppl; abstr 1090)

DOI

10.1200/jco.2015.33.15_suppl.1090

Abstract #

1090

Poster Bd #

204

Abstract Disclosures

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