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High serum levels of periostin are associated with a poor survival in breast cancer

Abstract

Purpose

Periostin is a secreted extracellular matrix protein, which was originally described in osteoblasts. It supports osteoblastic differentiation and bone formation and has been implicated in the pathogenesis of several human malignancies, including breast cancer. However, little is known about the prognostic value of serum periostin levels in breast cancer.

Methods

In this study, we analyzed serum levels of periostin in a cohort of 509 primary, non-metastatic breast cancer patients. Disseminated tumor cell (DTC) status was determined using bone marrow aspirates obtained from the anterior iliac crests. Periostin levels were stratified according to several clinical parameters and Pearson correlation analyses were performed. Kaplan–Meier survival curves were assessed by using the log-rank (Mantel–Cox) test. To identify prognostic factors, multivariate Cox regression analyses were used.

Results

Mean serum levels of periostin were 505 ± 179 pmol/l. In older patients (> 60 years), periostin serum levels were significantly increased compared to younger patients (540 ± 184 pmol/l vs. 469 ± 167 pmol/l; p < 0.0001) and age was positively correlated with periostin expression (p < 0.0001). When stratifying the cohort according to periostin serum concentrations, the overall and breast cancer-specific mortality were significantly higher in those patients with high serum periostin (above median) compared to those with low periostin during a mean follow-up of 8.5 years (17.7% vs. 11.4% breast cancer-specific death; p = 0.03; hazard ratio 1.65). Periostin was confirmed to be an independent prognostic marker for breast cancer-specific survival (p = 0.017; hazard ratio 1.79). No significant differences in serum periostin were observed when stratifying the patients according to their DTC status.

Conclusions

Our findings emphasize the relevance of periostin in breast cancer and reveal serum periostin as a potential marker for disease prediction, independent on the presence of micrometastases.

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Acknowledgements

The authors would like to thank Ms. Theresa Reiche for her secretarial assistance.

Funding

This study was supported by grants from the Deutsche Forschungsgemeinschaft and from the Deutsche Krebshilfe: 70113573 to AG and TDR, RA 2151/2-1 to TDR and LCH, Forschergruppe-1586 SKELMET to TDR and LCH and SPP-2084 µBONE to TDR, AG and LCH. RA 2151/2-1 to TDR and LCH, Forschergruppe-1586 SKELMET to TDR and LCH, SPP-2084 µBONE to TDR, AG and LCH from the Deutsche Forschungsgemeinschaft and the Deutsche Krebshilfe.

Author information

Study Design: AKB, OH and TDR. Study conduct: AG, AKB, DB, OH and TDR. Data collection: AKB, OH, RK, SKB. Data analysis: AG, AKB, KE, OH, and TDR. Data interpretation: AG, AKB, LCH, OH, SKB, and TDR. Drafting Manuscript: AG, AKB, OH, SKB, and TDR. Revising manuscript content: AG, AKB, KE, LCH, OH, RK, SKB, and TDR. Approving final version of manuscript: AG, AKB, DB, KE, LCH, OH, RK, SKB, and TDR. TDR takes responsibility of the integrity of the data analysis.

Correspondence to Andy Göbel.

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Conflict of interest

SKB is a consultant for QIAGEN, Hilden, Germany. The authors have received honoraria, unrestricted educational grants and research funding from to the individual or the institution by Alexion (LCH), Amgen (LCH, TDR), Roche (TDR), Shire (LCH, TDR), and UCB (LCH, TDR). All other authors declare no potential conflicts of interest.

Ethical approval

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.

Informed consent

Samples of patients were obtained before therapy after written informed consent from all subjects using protocols approved by the clinical ethic committee of the University Hospital Essen (05/2856).

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Rachner, T.D., Göbel, A., Hoffmann, O. et al. High serum levels of periostin are associated with a poor survival in breast cancer. Breast Cancer Res Treat (2020). https://doi.org/10.1007/s10549-020-05570-0

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Keywords

  • Periostin
  • Breast cancer
  • Disseminated tumor cells
  • Minimal residual disease
  • Prognostic marker