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Potential intrinsic subtype dependence on the association between metformin use and survival in surgically resected breast cancer: a Korean national population-based study

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Abstract

Purpose

Numerous studies have suggested that metformin treatment can increase breast cancer survival; however, it is unclear whether its effects interact with intrinsic subtype or diabetic status. Therefore, we conducted a large nationwide study to assess this in women with surgically resected invasive breast cancer.

Methods

Patients with newly diagnosed breast cancer between 2007 and 2016 were identified using the national health insurance claims database of South Korea. Metformin or other drug exposures was defined as medication for ≥ 90 days. Breast cancer subtypes were classified into four groups based on hormonal therapy and anti-HER2 treatments.

Results

A total of 117,333 patients were included (median follow-up duration, 90 months). Type 2 diabetes mellitus (T2DM) affected significantly overall survival (OS, 7 years, 89.7% vs. 92.4%, p < 0.001). A significant interaction was found between the use of metformin and insulin in patients with T2DM (p = 0.018). Thus, the subsequent analysis was limited to these patients and propensity score matching was performed. We found significantly increased OS in patients treated with metformin (7-year OS, 88.3% vs. 85.6%, p < 0.001). Interestingly, a significant effect was observed in the hormonal therapy (HT)+/HER2-targeted therapy (Tx)− group (p < 0.001), whereas no specific association was observed in the HT−/HER2 Tx− group (p = 0.220).

Conclusions

Metformin administration may be associated with reduced mortality in patients with surgically resected breast cancer, particularly in the HT+/HER2 Tx− group. Clinical trials investigating metformin as a combination agent in breast cancer should stratify patients by curative resection, intrinsic subtype, the presence of T2DM, and the use of insulin.

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Availability of data and material

The data that support the findings of this study are available from National Health insurance service sharing service (NHISS, South Korea) but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available.

Code availability

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Funding

This research was supported by the Chungnam National University Hospital Research Fund, 2019 (#2019-CF-027).

Author information

Authors and Affiliations

  1. Department of Radiation Oncology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Boramae-ro 5 gil, 20, Dongjak-gu, Seoul, Korea

    Byoung Hyuck Kim

  2. Department of Radiation Oncology, Chungnam National University College of Medicine, Munhwa-ro 282, Jungku, Daejeon, 35015, Korea

    Moon-June Cho & Jeanny Kwon

Authors
  1. Byoung Hyuck Kim
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  2. Moon-June Cho
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  3. Jeanny Kwon
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Contributions

BHK: data curation, formal analysis, methodology, writing—original draft. M-JC: supervision, conceptualization, writing—review and editing. JK: data curation formal analysis, writing—original draft, project administration.

Corresponding author

Correspondence to Jeanny Kwon.

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Conflicts of interest

The authors declare no potential conflicts of interest.

Ethical approval

This work was approved by our institutional review board (CNUH 2020-01-028).

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Informed consent was waived due to the retrospective nature of the study based on anonymized database.

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Cite this article

Kim, B.H., Cho, MJ. & Kwon, J. Potential intrinsic subtype dependence on the association between metformin use and survival in surgically resected breast cancer: a Korean national population-based study. Int J Clin Oncol 26, 2004–2016 (2021). https://doi.org/10.1007/s10147-021-02005-8

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  • DOI: https://doi.org/10.1007/s10147-021-02005-8

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