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Systemic immunity markers are associated with clinical outcomes of atezolizumab treatment in patients with triple-negative advanced breast cancer: a retrospective multicenter observational study

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Abstract

Immune checkpoint inhibitors (ICI) are reportedly efficacious against triple-negative breast cancer (TNBC) and are now recommended as first-line therapy. Systemic immunity markers, the absolute lymphocyte count (ALC) and the neutrophil-to-lymphocyte ratio (NLR), have been identified as predict ICI efficacy in patients with various cancers. We retrospectively enrolled 36 TNBC patients who received atezolizumab treatment between September 2019 and May 2021 at eight Japanese medical institutions. We evaluated systemic immunity markers, including dynamic changes in these markers, as predictors of survival benefit derived from atezolizumab treatment. Median time-to-treatment failure (TTF) and overall survival (OS) were 116 days and “not reached”, respectively. Patients with low NLR at baseline and decreased NLR at the start of the second cycle (SO2nd) had significantly longer OS than those with high NLR at baseline and increased NLR (SO2nd) (log-rank P < 0.001 and log-rank P = 0.049, respectively). Multivariate analyses identified high ALC at baseline and decreased NLR (SO2nd) as independent predictive markers for longer TTF (P = 0.043 and P = 0.002, respectively), and low NLR at baseline and decreased NLR (SO2nd) as independent predictive markers for longer OS (P < 0.001 and P = 0.013, respectively). The safety profile was consistent with those of previous trials. This retrospective multicenter observational study showed the clinical efficacy and safety of atezolizumab treatment. Furthermore, systemic immunity markers, including their dynamic changes, were found to be associated with clinical outcomes of atezolizumab treatment in patients with advanced or metastatic TNBC.

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Data availability

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

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Acknowledgements

The results of this research were presented in Japanese at the 2023 Breast Cancer Society Regional Meeting. We would like to thank Bierta Barfod, M.D., M.P.H. for English language editing.

Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

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Authors and Affiliations

  1. Department of Breast and Endocrine Surgery, Okayama University Hospital, 2-5-1, Shikata-cho, Kita-ku, Okayama, 700-8558, Japan

    Shogo Nakamoto, Tadahiko Shien, Naruto Taira & Hiroyoshi Doihara

  2. Department of Breast Surgery, Hiroshima City Hiroshima Citizens Hospital, Hiroshima, Japan

    Mitsuya Itoh

  3. Department of Breast and Thyroid Surgery, Kawasaki Medical School Hospital, Kurashiki, Japan

    Yutaka Yamamoto & Naruto Taira

  4. Department of Breast Oncology, NHO Shikoku Cancer Center, Matsuyama, Japan

    Shozo Ohsumi

  5. Department of Breast and Endocrine Surgery, Red Cross Okayama Hospital, Okayama, Japan

    Seiji Yoshitomi

  6. Department of Breast Surgery, Matsue Red Cross Hospital, Matsue, Japan

    Hajime Hikino

  7. Department of Breast and Endocrine Surgery, National Hospital Organization Fukuyama Medical Center, Fukuyama, Japan

    Kazuya Miyoshi

  8. Clinical Research Center, Shizuoka Cancer Center, Nagaizumi-cho, Japan

    Akifumi Notsu

  9. Department of Surgery, Kawasaki Medical School General Medical Center, Okayama, Japan

    Hiroyoshi Doihara

  10. Department of Breast and Thyroid Surgery, Fukuyama Citizens Hospital, Fukuyama, Japan

    Masahiko Ikeda

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  1. Shogo Nakamoto
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Contributions

All authors contributed to the study conception and design. SN, MI, YY, SO, SY, HH, and KM were responsible for the material preparation and collected the data. SN performed the analysis. AN provided advice and assistance on the statistical analysis. SN, TS, AN, NT, HD, and MI contributed to the interpretation and discussion of the results. SN wrote the first draft of the manuscript, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Shogo Nakamoto.

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The authors have no relevant financial or non-financial interests to disclose.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study was approved by the Ethics Committee of Okayama University Hospital (No. 2112–037). This study was conducted in full compliance with the relevant laws and after obtaining approval from the institutional review boards of the centers where the patients had been treated and the data collected. Informed consent was obtained in the form of an opt-out on the website from all individual subjects included in the study.

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Nakamoto, S., Shien, T., Itoh, M. et al. Systemic immunity markers are associated with clinical outcomes of atezolizumab treatment in patients with triple-negative advanced breast cancer: a retrospective multicenter observational study. Clin Exp Med 23, 5129–5138 (2023). https://doi.org/10.1007/s10238-023-01230-x

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