Progranulin and Breast Cancer Mortality: 13-Year Follow-Up of a Cohort Study

Abstract

Background

We have reported that serum progranulin (PGRN) levels are clinically significant in predicting recurrence in patients with HR-positive breast cancer. The aim of the present study was to examine whether PGRN levels might be associated with breast cancer mortality.

Methods

This was a cohort study of 695 newly diagnosed breast cancer patients who underwent curative surgery between 2001 and 2004. The relationship between breast cancer mortality and pre-operative serum PGRN levels in these patients with a median follow-up of 12.7 years was evaluated until May 2020.

Results

A total of 118 (17%) deaths were identified in the cohort. According to the HR status, (10, 15, and 20)-year overall survival (OS) rates were (91.4, 81.1, and 75.9) % for HR-positive patients, and (76.5, 74.2, and 69.8) % for HR-negative patients, respectively (p = 0.003). Higher levels of PGRN were significantly associated with poor OS in the HR-positive group (p for trend = 0.001). In particular, hazard ratios for PGRN quartiles suggested a dose–response relationship, with the highest quartile having the worst OS in the HR-positive group (highest vs lowest: 15-year OS, (68.3 vs 90.0) %; 20-year OS, (62.3 vs 84.8) %, even after adjusting for age, tumor stage, and metabolic confounders.

Conclusion

Pre-operative serum PGRN levels had clinical significance for predicting cancer mortality in breast cancer patients independent of tumor stage and metabolic parameters, especially in HR-positive tumors.

Keywords:

• breast cancer
• progranulin
• mortality
• long-term follow-up

Data Sharing Statement

The data presented in this study are available on reasonable request from the corresponding author. The data are not publicly available, due to the issue of patient privacy.

Ethics Approval and Consent to Participate

This study protocol was approved by the Institutional Review Board of the National Cancer Center, Republic of Korea (IRB Protocol No. NCCNCS-09-220) and complied with the tenets of the Declaration of Helsinki. Written informed consent was obtained from all patients.

Acknowledgments

The authors thank the participants and their families, and all investigators and site personnel. D.-H. K. and K. S. L. contributed equally to this work as co-first authors. C.-Y. P. and S. W. O. contributed equally to this work as co-corresponding authors.

Disclosure

Dr. Keun Seok Lee has consulting or advisory role for AstraZeneca, Eisai, Lilly, Merck, Novartis, Pfizer, Everest Medicine, Bixink, Daiichi Sankyo, and Roche; has received research funding from Novartis; has received research drug supply from Dong-A ST. The authors declare that they have no other competing interests.

Additional information

Funding

There is no funding to report.