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

  • Anbok Lee
  • Sunmi Jo
  • Changhu Lee
  • Hyun-Hee Shin
  • Tae Hyun Kim
  • Ki Jung Ahn
  • Sung-Kwang Park
  • Heunglae Cho
  • Hye-Kyoung Yoon
  • Woo Gyeong Kim
  • Jiyoung ParkEmail author
  • Yunseon ChoiEmail author
Original Article

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.

Keywords

HER-2 positive breast cancer Trastuzumab Diabetes Survival Prognostic factor 

Notes

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.

Compliance with ethical standards

Conflict of interest

The authors have declared that no competing interests exist.

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Copyright information

© The Japanese Breast Cancer Society 2019

Authors and Affiliations

  1. 1.Department of Surgery, Busan Paik HospitalInje University College of MedicineBusanSouth Korea
  2. 2.Department of Radiation Oncology, Haeundae Paik HospitalInje University College of MedicineBusanSouth Korea
  3. 3.Department of Biological Sciences, School of Life SciencesUlsan National Institutes of Science and TechnologyUlsanSouth Korea
  4. 4.Department of Radiation Oncology, Busan Paik HospitalInje University College of MedicineBusanSouth Korea
  5. 5.Department of Pathology, Busan Paik HospitalInje University College of MedicineBusanSouth Korea
  6. 6.Department of Pathology, Haeundae Paik HospitalInje University College of MedicineBusanSouth Korea

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