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Value of CXCL8–CXCR1/2 axis in neoadjuvant chemotherapy for triple-negative breast cancer patients: a retrospective pilot study

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Abstract

Background

In this study we investigate the prediction and prognostic value of CXCL8–CXCR1/2 axis for Triple-negative breast cancer (TNBC) patients underwent neoadjuvant chemotherapy (NAC) following standard radical surgery.

Methods

A total of 303 TNBC patients were included in this study. The NAC regimen was weekly paclitaxel plus carboplatin (PC) for all patients. Serum CXCL8 level was measured at baseline and at surgery via Enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry was used to detect CXCR1 and CXCR2 expression in patients with residual tumors after NAC. Correlations between variables and treatment response were studied, and Cox proportional hazards regression analysis was implemented for prognostic evaluation.

Results

Of the 303 patients, 103 (34.0%) patients experienced pathological complete response (pCR) after completion of NAC. CXCL8 level was significantly upgraded after NAC in CXCR1/2+ patients and downgraded after NAC in CXCR1/2− patients. Higher pCR rate was more likely observed in patients with lower CXCL8 level at surgery (P = 0.004, HR 0.939, 95% CI 0.900–0.980). In the multivariate survival model, CXCR1/2 expression was of an independent prognostic value for survival (CXCR1/2+, HR 2.149, 95% CI 0.933–4.949; CXCR1/2++, HR 3.466, 95% CI 1.569–7.655, CXCR1/2− was used as a reference; P = 0.003). Patients with higher level of CXCR1/2 expression were more likely to suffer unfavorable outcome.

Conclusions

This study contributes to the clarification of the value of serum CXCL8 level to predict pCR for TNBC patients, and prognostic performance of CXCR1/2 in non-pCR responders after NAC. The CXCL8–CXCR1/2 might play an important role in tailoring and modifying the NAC strategy for advanced TNBCs; however, further confirmatory studies are needed.

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Data availability

The dataset supporting the conclusions of this article is included within the article.

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Acknowledgements

The authors are grateful to Yin Zhou, Guang-Yu Liu and Can-Ming Chen for their excellent data management.

Funding

This research was supported by the National Natural Science Foundation of China (81872134), Natural Science Foundation of Shanghai (17ZR1405900), Research Foundation of Shanghai Municipal Commission of Health and Family Planning (20164Y0200), Project of Excellent Youth of Shanghai Municipal Commission of Health and Family Planning (2018YQ42), and Shanghai Sailing Program (18YF1405000). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Authors and Affiliations

  1. Department of Breast Surgery, Fudan University Shanghai Cancer Center/Cancer Institute, 399 Ling-Ling Road, Shanghai, 200032, People’s Republic of China

    Ruo-Xi Wang, Peng Ji, Yue Gong, Zhi-Ming Shao & Sheng Chen

  2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China

    Ruo-Xi Wang, Peng Ji, Yue Gong, Zhi-Ming Shao & Sheng Chen

  3. Institutes of Biomedical Science, Fudan University, Shanghai, People’s Republic of China

    Zhi-Ming Shao

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  1. Ruo-Xi Wang
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Contributions

WRX and CS contributed to the conception of the study, data analysis and interpretation, and writing the manuscript. JP and GY made tissue sections and participated in ELISA and immunohistochemical analysis. CS and SZM contributed to the collection and assembly of data. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Sheng Chen.

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The authors declare that they have no competing interests.

Ethics approval

Our study was approved by the independent ethical committee/institutional review board of Fudan University Shanghai Cancer Center (Shanghai Cancer Center Ethical Committee). All patients gave their written informed consent before inclusion in this study.

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Wang, RX., Ji, P., Gong, Y. et al. Value of CXCL8–CXCR1/2 axis in neoadjuvant chemotherapy for triple-negative breast cancer patients: a retrospective pilot study. Breast Cancer Res Treat 181, 561–570 (2020). https://doi.org/10.1007/s10549-020-05660-z

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  • DOI: https://doi.org/10.1007/s10549-020-05660-z

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