HER2‑positive breast cancer that resists therapeutic drugs and ionizing radiation releases sphingomyelin‑based molecules to circulating blood serum

Monzen,Satoru; Tatara,Yota; Mariya,Yasushi; Chiba,Mitsuru; Wojcik,Andrzej; Lundholm,Lovisa

doi:10.3892/mco.2020.2140

HER2‑positive breast cancer that resists therapeutic drugs and ionizing radiation releases sphingomyelin‑based molecules to circulating blood serum

Authors:
- Satoru Monzen
- Yota Tatara
- Yasushi Mariya
- Mitsuru Chiba
- Andrzej Wojcik
- Lovisa Lundholm
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Affiliations: Department of Radiation Science, Hirosaki University Graduate School of Health Sciences, Hirosaki, Aomori 036‑8564, Japan, Department of Glycotechnology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036‑8562, Japan, Department of Radiology, Mutsu General Hospital, Mutsu, Aomori 035‑0071, Japan, Department of Bioscience and Laboratory Medicine, Hirosaki University Graduate School of Health Sciences, Hirosaki, Aomori 036‑8564, Japan, Centre for Radiation Protection Research, Department of Molecular Biosciences, The Wenner‑Gren Institute, Stockholm University, 114 18 Stockholm, Sweden
Published online on: September 21, 2020 https://doi.org/10.3892/mco.2020.2140
Article Number: 70
Copyright: © Monzen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Breast cancer is the second most common cancer in the world based on incidence, reaching more than 2 million new cases in 2018, while continuing to increase. Invasive ductal carcinoma is the most common type of this cancer, making up approximately 70‑80% of all breast cancer diagnoses. In particular, the type of breast cancer overexpressing human epidermal growth factor receptor 2 (HER2) has potential of strong proliferation, migration and invasion and early treatment is necessary. The authors identified and studied a single patient displaying complete therapeutic resistance to monoclonal anti‑HER2 antibody therapy, chemotherapy and radiotherapy. A patient who exhibited resistance to postoperative adjuvant therapy after mastectomy was selected from HER2‑positive breast cancer, and this patient had the grade of T_4bN_2aM₀, Stage IIIB. The patient samples, blood serum and cancer tissue, were analyzed by metabolome and immunostaining technique, respectively. The characteristics of peripheral blood serum and solid tumor were investigated, aiming to find new serum biomarker(s) using the metabolomics technique. A correlation between the appearance of HER2‑positive cancer tissue and serum concentration of the sphingomyelin family was found. In addition, HER2‑positive tumor tissue in both the primary and recurrent cancer express the sphingomyelinase. These results suggest that sphingomyelins from this cancer tissue leads to therapy resistance, induction of invasion and strong proliferation.

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