Risk factors for recurrence in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative early breast cancer in Japan: a systematic literature review and meta-analysis

Abstract

Background

The clinicopathological factors indicating risk of recurrence are used to guide the choice of perioperative therapy in patients with breast cancer. Although several risk factors for recurrence have been reported in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) early breast cancer in Japan, there has been no systematic review quantifying potential risk factors.

Methods

We performed a systematic literature review and meta-analysis using the MEDLINE, Embase, Cochrane CENTRAL, and Japan Medical Abstract Society databases to identify risk factors for recurrence in HR+/HER2− early breast cancer in Japan. The primary outcome was relapse-free or disease-free survival (RFS/DFS), and the secondary outcomes were overall survival and breast cancer-specific survival (BCSS).

Results

Searches identified 42 eligible publications. Meta-analyses identified lymph node metastasis (hazard ratio: 2.76 [95% confidence interval: 1.97–3.88]), large tumor size (1.67 [1.24–2.23]), high histological grade (1.50 [1.04–2.16]), and high nuclear grade (2.02 [1.61–2.54]) as risk factors for RFS/DFS. Lymph node metastasis (2.43 [1.28–4.63]), large tumor size (1.80 [1.24–2.62]), and high histological grade (2.02 [1.44–2.84]) were also risk factors for overall survival, and high progesterone status was a possible favorable prognostic factor for BCSS (0.20 [0.10–0.42]).

Conclusions

Identified risk factors were consistent with the previous reports, and this study provides quantitative summary of risk factors for HR+/HER2– early breast cancer recurrence in Japan. (PROSPERO Registration ID, CRD42022338391.)

Keywords:

• Risk factors
• breast neoplasms
• systematic review
• meta-analysis
• receptor
• ErbB-2

Transparency

Declaration of funding

This study was funded by Eli Lilly Japan and outsourced from Eli Lilly Japan to the Biostatistics Unit of Keio University Hospital.

Declaration of financial/other relationships

H. S. has received speaker’s honorarium and medical writing support from Daiichi Sankyo as well as research funding from Eisai. Y. T, Z. C., and T.K. are employees of Eli Lilly Japan, and minor stockholders of Eli Lilly and Company. J. T.’s institution received study grants from Eli Lilly, Eisai, Daiichi Sankyo, Kyowa Kirin, Taiho, MSD, and Nihon Kayaku, Ono, the West Japan Oncology Group and he was paid personal fee for lecture by the Eli Lilly, Eisai, Daiichi Sankyo, Kyowa Kirin, Taiho, MSD, and Nihon Kayaku Japan.

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

Y. T., Z. C., and T. K. contributed to the study conceptualization and design. N. M., T. I., and K. N. performed a literature search and contributed to data acquisition. K. N. performed statistical analyses. All authors contributed to the interpretation of data. N. M. contributed to manuscript drafting. All authors critically reviewed and revised the draft manuscript and approved the final version for submission.

Acknowledgements

None.

Data availability statement

The datasets used and/or analyzed during this study are available from the corresponding author upon reasonable request.