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Diabetes as a prognostic factor in HER-2 positive breast cancer patients treated with targeted therapy

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Abstract

Purpose

Recent studies revealed that metabolic stress influences the outcomes of breast cancer treatment. We sought to evaluate the prognostic effect of type 2 diabetes and find the molecular mechanism of relapses in postoperative HER-2+ breast cancer patients treated with HER-2 targeted therapy.

Materials and methods

We evaluated 190 HER-2+ breast cancer patients (pT1-4N0-2M0) who were treated with surgical resection and trastuzumab (HER-2 targeted therapy) between 2006 and 2015. Survival outcomes and failure patterns were compared between such patients with (n = 12) and without (n = 178) type 2 diabetes.

Results

The median follow-up period was 42.4 months (range 12.0–124.7 months). Twenty-one patients (11.1%) showed relapse (including nine patients with locoregional failure), and three patients (1.6%) died as a result of cancer relapse. One-third of the patients with diabetes experienced relapse (4/12, 33.3%). The 3-year disease-free survival (DFS) and overall survival (OS) rates were 90.7% and 98.6%, respectively. Diabetic patients showed shorter DFS compared with non-diabetic patients (p = 0.006, 74.1% vs. 91.9%). OS was also shorter in diabetic patients compared with non-diabetic patients (p = 0.017, 91.7% vs. 99.1%). Of our interest, the levels of HER-3 and its ligand neuregulin-1 were significantly increased in the tumor specimen in HER-2+ breast cancer patients suffering with type 2 diabetes than that in the euglycemic control group.

Conclusions

Type 2 diabetes was associated with detrimental effects on survival in postoperative HER-2+ breast cancer patients who were treated with trastuzumab. The poor prognostic effect of diabetes in HER-2+ breast cancer patients could be associated with the high levels of HER-3 and neuregulin 1, thus it should be considered and evaluated more.

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Acknowledgements

The biospecimens and data used in this study were provided by the Biobank of Inje University PAIK Hospital (InJeBiobank), a member of Korea Biobank Network.

Funding

This work was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI, HI14C1277), the Bio-Synergy Research Project (NRF-2017M3A9C4065956) of the Ministry of Science, ICT and Future Planning and Basic Science Research Program (NRF-2018R1A2B6003878) through the National Research Foundation to J.P.

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Author notes

  1. Anbok Lee and Sunmi Jo contributed equally to this work.

  2. Jiyoung Park and Yunseon Choi contributed equally to this work.

Authors and Affiliations

  1. Department of Surgery, Busan Paik Hospital, Inje University College of Medicine, Busan, South Korea

    Anbok Lee & Tae Hyun Kim

  2. Department of Radiation Oncology, Haeundae Paik Hospital, Inje University College of Medicine, Busan, South Korea

    Sunmi Jo

  3. Department of Biological Sciences, School of Life Sciences, Ulsan National Institutes of Science and Technology, Ulsan, South Korea

    Changhu Lee, Hyun-Hee Shin & Jiyoung Park

  4. Department of Radiation Oncology, Busan Paik Hospital, Inje University College of Medicine, Busan, South Korea

    Ki Jung Ahn, Sung-Kwang Park, Heunglae Cho & Yunseon Choi

  5. Department of Pathology, Busan Paik Hospital, Inje University College of Medicine, Busan, South Korea

    Hye-Kyoung Yoon

  6. Department of Pathology, Haeundae Paik Hospital, Inje University College of Medicine, Busan, South Korea

    Woo Gyeong Kim

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  1. Anbok Lee
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Correspondence to Jiyoung Park or Yunseon Choi.

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Lee, A., Jo, S., Lee, C. et al. Diabetes as a prognostic factor in HER-2 positive breast cancer patients treated with targeted therapy. Breast Cancer 26, 672–680 (2019). https://doi.org/10.1007/s12282-019-00967-2

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  • DOI: https://doi.org/10.1007/s12282-019-00967-2

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