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PD-L1 diagnostics in the neoadjuvant setting: implications of intratumoral heterogeneity of PD-L1 expression in triple negative breast cancer for assessment in small biopsies

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@article{fd5285c7b10b44f18c9ea0bc5672d55b,
title = "PD-L1 diagnostics in the neoadjuvant setting: implications of intratumoral heterogeneity of PD-L1 expression in triple negative breast cancer for assessment in small biopsies",
abstract = "PURPOSE: PD-L1 expression is a predictive biomarker for anti-PD-L1 immunotherapy in triple negative breast cancer (TNBC). In the neoadjuvant setting, immunohistochemical (IHC) evaluation of PD-L1 expression can only be performed on small tissue biopsies. In our study we investigated heterogeneity of PD-L1 expression in TNBC, and how reliably PD-L1 expression in small tissue samples reflects PD-L1 expression in larger tumor sections in TNBC.METHODS: Tissue microarrays (TMAs) were constructed from surgical specimens of 110 patients with TNBC. TMAs contained 4 cores (1 mm in diameter) per patient. To evaluate PD-L1 expression, TMAs were stained with PD-L1 IHC 22C3 PharmDx. Single-core PD-L1 expression was compared to overall PD-L1 expression of each patient's tumor, to ascertain how often small samples of tumor tissue show the same PD-L1 expression as larger tumor samples.RESULTS: Our study found substantial heterogeneity of PD-L1 expression between different TMA cores from the same patient. Heterogeneity was greater in immune cells (ICs) than in tumor cells, in large part due to the uneven distribution of ICs in the tumor. For IC PD-L1 expression, we found that sensitivity can be as low as 0.81 for detecting PD-L1 expression at the 1{\%} threshold most commonly used in breast cancer. Negative predictive value for ICs was 0.7.CONCLUSIONS: There is substantial heterogeneity of PD-L1 expression between small tissue samples from the same TNBC tumor, especially for IC expression. This poses challenges for evaluation of PD-L1 expression in the neoadjuvant setting. Negative biopsies should prompt further investigation, and multiple biopsies might be necessary.",
keywords = "Biomarker, Heterogeneity, Immune therapy, Neoadjuvant, PD-L1, Triple negative breast cancer",
author = "Stovgaard, {E S} and M Bokharaey and K List-Jensen and A Roslind and I K{\"u}mler and E H{\o}gdall and D Nielsen and E Balslev",
year = "2020",
month = "6",
doi = "10.1007/s10549-020-05655-w",
language = "English",
volume = "181",
pages = "553--560",
journal = "Breast Cancer Research and Treatment",
issn = "0167-6806",
publisher = "Springer New York LLC",
number = "3",

}

RIS

TY - JOUR

T1 - PD-L1 diagnostics in the neoadjuvant setting

T2 - implications of intratumoral heterogeneity of PD-L1 expression in triple negative breast cancer for assessment in small biopsies

AU - Stovgaard, E S

AU - Bokharaey, M

AU - List-Jensen, K

AU - Roslind, A

AU - Kümler, I

AU - Høgdall, E

AU - Nielsen, D

AU - Balslev, E

PY - 2020/6

Y1 - 2020/6

N2 - PURPOSE: PD-L1 expression is a predictive biomarker for anti-PD-L1 immunotherapy in triple negative breast cancer (TNBC). In the neoadjuvant setting, immunohistochemical (IHC) evaluation of PD-L1 expression can only be performed on small tissue biopsies. In our study we investigated heterogeneity of PD-L1 expression in TNBC, and how reliably PD-L1 expression in small tissue samples reflects PD-L1 expression in larger tumor sections in TNBC.METHODS: Tissue microarrays (TMAs) were constructed from surgical specimens of 110 patients with TNBC. TMAs contained 4 cores (1 mm in diameter) per patient. To evaluate PD-L1 expression, TMAs were stained with PD-L1 IHC 22C3 PharmDx. Single-core PD-L1 expression was compared to overall PD-L1 expression of each patient's tumor, to ascertain how often small samples of tumor tissue show the same PD-L1 expression as larger tumor samples.RESULTS: Our study found substantial heterogeneity of PD-L1 expression between different TMA cores from the same patient. Heterogeneity was greater in immune cells (ICs) than in tumor cells, in large part due to the uneven distribution of ICs in the tumor. For IC PD-L1 expression, we found that sensitivity can be as low as 0.81 for detecting PD-L1 expression at the 1% threshold most commonly used in breast cancer. Negative predictive value for ICs was 0.7.CONCLUSIONS: There is substantial heterogeneity of PD-L1 expression between small tissue samples from the same TNBC tumor, especially for IC expression. This poses challenges for evaluation of PD-L1 expression in the neoadjuvant setting. Negative biopsies should prompt further investigation, and multiple biopsies might be necessary.

AB - PURPOSE: PD-L1 expression is a predictive biomarker for anti-PD-L1 immunotherapy in triple negative breast cancer (TNBC). In the neoadjuvant setting, immunohistochemical (IHC) evaluation of PD-L1 expression can only be performed on small tissue biopsies. In our study we investigated heterogeneity of PD-L1 expression in TNBC, and how reliably PD-L1 expression in small tissue samples reflects PD-L1 expression in larger tumor sections in TNBC.METHODS: Tissue microarrays (TMAs) were constructed from surgical specimens of 110 patients with TNBC. TMAs contained 4 cores (1 mm in diameter) per patient. To evaluate PD-L1 expression, TMAs were stained with PD-L1 IHC 22C3 PharmDx. Single-core PD-L1 expression was compared to overall PD-L1 expression of each patient's tumor, to ascertain how often small samples of tumor tissue show the same PD-L1 expression as larger tumor samples.RESULTS: Our study found substantial heterogeneity of PD-L1 expression between different TMA cores from the same patient. Heterogeneity was greater in immune cells (ICs) than in tumor cells, in large part due to the uneven distribution of ICs in the tumor. For IC PD-L1 expression, we found that sensitivity can be as low as 0.81 for detecting PD-L1 expression at the 1% threshold most commonly used in breast cancer. Negative predictive value for ICs was 0.7.CONCLUSIONS: There is substantial heterogeneity of PD-L1 expression between small tissue samples from the same TNBC tumor, especially for IC expression. This poses challenges for evaluation of PD-L1 expression in the neoadjuvant setting. Negative biopsies should prompt further investigation, and multiple biopsies might be necessary.

KW - Biomarker

KW - Heterogeneity

KW - Immune therapy

KW - Neoadjuvant

KW - PD-L1

KW - Triple negative breast cancer

UR - http://www.scopus.com/inward/record.url?scp=85083956971&partnerID=8YFLogxK

U2 - 10.1007/s10549-020-05655-w

DO - 10.1007/s10549-020-05655-w

M3 - Journal article

VL - 181

SP - 553

EP - 560

JO - Breast Cancer Research and Treatment

JF - Breast Cancer Research and Treatment

SN - 0167-6806

IS - 3

ER -

ID: 59782850