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Neo-peripheral adaptive immune score predicts neoadjuvant chemotherapy for locally advanced breast cancer

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Abstract

Purpose

Whether peripheral immune cell subsets can predict pathological complete response (pCR) in breast cancer patients remains to be elucidated. We aimed to dissect the relationship between peripheral immune cell subsets and pCR.

Methods

Two hundred and twenty-six eligible patients from two prospective clinical trials (SHPD001 and SHPD002) in China were randomly divided into a training cohort and a validation cohort. The breast cancer subtypes in this study included hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative (n = 95), HER2-positive (n = 100), and triple negative (n = 31) breast cancer. We defined the “Neo-Peripheral Adaptive Immune Score” for neoadjuvant chemotherapy (neoPAI Score) based on the percentages of CD4 + T cells, CD8 + T cells, B cells, and the CD4 + /CD8 + ratio in peripheral blood. We also evaluated the ability of the neoPAI Score derived from tumor-infiltrating immune cells (TIICs) to predict survival by employing The Cancer Genome Atlas-Breast Cancer (TCGA-BRCA) database.

Results

In the training cohort, multivariate analysis showed that HR status [odds ratio (OR) 0.325; 95% confidence interval (CI) 0.135–0.761; P = 0.010], HER2 status (OR 2.657; 95% CI 1.266–5.730; P = 0.011), Ki67 index (OR 3.191; 95% CI 1.509–6.956; P = 0.003), histological grade (OR 2.297; 95% CI 1.031–5.290; P = 0.045) and neoPAI Score (OR 4.451; 95% CI 1.608–13.068; P = 0.005) were independent predictors of pCR. In the validation cohort, histological grade (OR 3.779; 95% CI 3.793–1.136 × 103; P = 0.008) and neoPAI Score (OR 90.828; 95% CI 3.827–9.843 × 103; P = 0.019) were independent predictors of pCR. The Immune Model that integrated the neoPAI Score was more accurate in predicting pCR than the Clinical Model that exclusively contained clinicopathological parameters in both cohorts. In TCGA-BRCA database, the neoPAI Score constructed from TIICs can predict the progression-free interval (P = 0.048) of breast cancer.

Conclusion

The neoPAI Score defined by the percentages of peripheral immune cell subsets could be used as a potential biomarker for neoadjuvant chemotherapy efficacy.

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Data availability

Data are contained within the article, supplementary materials and from the corresponding author upon request.

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Funding

This work was supported by the Shanghai Sailing Program (Grant No. 22YF1424500), National Natural Science Foundation of China (Grant No. 82103695), Clinical Research Plan of Shanghai Hospital Development Center (Grant No. SHDC2020CR3003A), Science and Technology Commission of Shanghai Municipality (Grant No. 20DZ2201600), Shanghai Municipal Key Clinical Specialty, Shanghai Rising-Star Program (Grant No. 22QC1400200), Multidisciplinary Cross Research Foundation of Shanghai Jiao Tong University (Grant No. YG2019QNA28), Nurturing Fund of Renji Hospital (Grant Nos. PYIII20-09 and RJPY-LX-002), Clinical Research Innovation Nurturing Fund of Renji Hospital and United Imaging (Grant No. 2021RJLY-002).

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Author notes

  1. Huiling Wang and Xiaonan Sheng have contributed equally to this work.

Authors and Affiliations

  1. Department of Breast Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, People’s Republic of China

    Huiling Wang, Xiaonan Sheng, Tingting Yan, Yaqian Xu, Yaohui Wang, Yanping Lin, Jie Zhang, Yumei Ye, Shuguang Xu, Liheng Zhou, Wenjin Yin & Jinsong Lu

  2. Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People’s Republic of China

    Yaqian Xu

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  1. Huiling Wang
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Contributions

HW, YW, WY and JL: conceptualization, HW, YW and XS: methodology, YX, TY, JZ and YL: investigation, HW: formal analysis, HW and XS: writing—original draft preparation, HW, YW, WY and JL: writing—review and editing, YY, SX, LZ, WY and JL: supervision. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Yaohui Wang, Wenjin Yin or Jinsong Lu.

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Wang, H., Sheng, X., Yan, T. et al. Neo-peripheral adaptive immune score predicts neoadjuvant chemotherapy for locally advanced breast cancer. Breast Cancer Res Treat 197, 343–354 (2023). https://doi.org/10.1007/s10549-022-06791-1

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