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PD-L1 protein expression in relation to recurrence score values in early-stage ER + breast cancer

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Abstract

Purpose

We assessed associations between PD-L1 protein expression, RS, tumor grade, and stromal tumor-infiltrating lymphocyte (TIL) count in early-stage ER + cancers.

Methods

FFPE tissue blocks of 213 patients with RS in 2012–2017 were identified. PD-L1 immunohistochemistry was performed with SP142 assay, cases with ≥ 1% tumor-infiltrating immune cell positivity in the tumor area were considered PD-L1 + . TIL scores were determined following the international TIL counting guidelines. PD-L1 expression positivity rates were compared across RS (< 11, 11–25, > 25) and TIL categories (< 10%, 10–29%, > 30%), and tumor grade using Wilcoxon and Chi-square tests. Multivariate analysis was performed using logistic regression.

Results

PD-L1 and TIL results were available for 201 and 203 patients. Overall, 53% of cases were PD-L1 +. PD-L1 expression was higher among cases with RS > 25, versus RS < 11 (p = 0.00019) and RS 11–25 (p = 0.0017). PD-L1 positivity also correlated with TIL score, tumor grade, and tumor size. Among cancers with TIL > 30%, 92% were PD-L1 + versus 44% PD-L1 + among TIL < 10% (p = 2.8 × 10–6). Grade 3 cancers had higher PD-L1 positivity (79% PD-L1 +) versus grade 2 (49% PD-L1 +) or 1 tumors (48% PD-L1 +) (p = 0.00047). T2 and T3 tumors had more frequent PD-L1 positivity (67% and 83%, respectively) versus T1 cancers (46%) (p = 0.008). In multivariate analysis, only TIL and RS remained as independent predictors of PD-L1 positivity.

Conclusion

PD-L1 expression is significantly more frequent and higher in larger tumors (T2, T3), grade 3 cancers, and in cancers with RS > 25. PD-L1 expression also correlates with TIL score.

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Data availability

The datasets generated during the current study are available from the corresponding author on reasonable request.

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Funding

This study was funded by an International Immuno-Oncology Network grant from Bristol Myers Squibb to L.P and M.H.

Author information

Authors and Affiliations

  1. Yale Cancer Center, Yale School of Medicine, New Haven, CT, 06511, USA

    Mariya Rozenblit, Kim Blenman, Tao Qing, Eiman Ibrahim, Hao-Kuen Lin & Lajos Pusztai

  2. Department of Pathology, Yale School of Medicine, New Haven, CT, 06511, USA

    Malini Harigopal & Emily Reisenbichler

  3. Foundation Medicine, Inc., 150 Second Street, Cambridge, MA, 02141, USA

    Shakti Ramkissoon, Mustimbo Roberts & Jeffrey Ross

  4. Bristol-Myers Squibb, 100 Binney St, Cambridge, MA, 02142, USA

    Richard S. P. Huang

  5. Department of Pathology and Laboratory Medicine, Brown University, Providence, RI, USA

    Kamaljeet Singh

  6. Yale University, New Haven, CT, USA

    Sem Asmelash

Authors
  1. Mariya Rozenblit
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  2. Kim Blenman
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  3. Malini Harigopal
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  4. Emily Reisenbichler
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  5. Kamaljeet Singh
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  6. Tao Qing
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  7. Eiman Ibrahim
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  12. Jeffrey Ross
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  13. Richard S. P. Huang
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  14. Lajos Pusztai
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Contributions

M.R., K.B., and L.P. designed the study and wrote the manuscript. K.B., E.R., M.H., and K.S. provided TIL counts and reviewed the pathology slides and information. M.R., J.R., R.H., L.P., M.R., K.B., and S.A. provided support in designing the project, acquiring the data, and preparing the manuscript. T.Q. and H.-K.L. provided statistical support. All authors reviewed and edited the manuscript.

Corresponding author

Correspondence to Mariya Rozenblit.

Ethics declarations

Competing interests

S.R. J.R., and R. S.P.H are employees of Foundation Medicine, a wholly owned subsidiary of Roche and receive equity from Roche. M. Roberts is an employee and stockholder of BMS. L.P. has received consulting fees and honoraria from Seagen, Pfizer, Astra Zeneca, Merck, Novartis, Bristol Myers Squibb, Genentech, Eisai, Pieris, Immunomedics, Clovis, Syndax, H3Bio, Radius Health, Personalis, Natera, and Daiichi and institutional research funding from Seagen, AstraZeneca, Merck, Pfizer, and Bristol Myers Squibb.

Ethics approval

This study was approved by the Yale IRB.

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Kim Blenman: Shared first co-authorship.

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Rozenblit, M., Blenman, K., Harigopal, M. et al. PD-L1 protein expression in relation to recurrence score values in early-stage ER + breast cancer. Breast Cancer Res Treat 196, 221–227 (2022). https://doi.org/10.1007/s10549-022-06712-2

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  • DOI: https://doi.org/10.1007/s10549-022-06712-2

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