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. 2025 Sep 1;5(5):614-619.
doi: 10.21873/cdp.10476. eCollection 2025 Sep-Oct.

Eradication of Extensive Lymph-Node, Bone and Pleural Metastases of a Breast-Cancer Patient Treated With Radiation, Immunotherapy and Oral Recombinant Methioninase

Yohei Asano  1   2   3 , Toshihiko Sato  4 , Qinghong Han  1 , Shukuan Li  1 , Chihiro Hozumi  5 , Kohei Mizuta  1   2 , Byung Mo Kang  1   2 , Jin Soo Kim  1   2 , Yuta Miyashi  1   2 , Norio Yamamoto  3 , Katsuhiro Hayashi  3 , Hiroaki Kimura  3 , Shinji Miwa  3 , Kentaro Igarashi  3 , Takashi Higuchi  3 , Sei Morinaga  3 , Hiroyuki Tsuchiya  3 , Satoru Demura  3 , Robert M Hoffman  1   2
Affiliations

Eradication of Extensive Lymph-Node, Bone and Pleural Metastases of a Breast-Cancer Patient Treated With Radiation, Immunotherapy and Oral Recombinant Methioninase

Yohei Asano et al. Cancer Diagn Progn. .

Abstract

Background/aim: Metastatic breast cancer is a recalcitrant disease with a poor prognosis. Novel targets and therapies are necessary to improve the survival rate of patients with metastatic breast cancer. Previous pre-clinical and clinical studies, have demonstrated the effectiveness of oral recombinant methioninase (o-rMETase) against breast cancer. The present case report shows that combination treatment with radiation, immunotherapy, a low-methionine diet, and o-rMETase led to rapid eradication of extensive bone and other metastases in a patient with breast cancer.

Case report: A patient with breast cancer with extensive metastases to the liver, lymph nodes, pleura and bones was diagnosed using [18F]fluorodeoxyglucose positron emission tomography (FDG-PET). The patient was immediately started on systemic drug therapy with tamoxifen and leuprorelin, but it failed to suppress the tumor. Then, combination treatment with radiation, immunotherapy with biological response modifier (BRM)-activated killer (BAK), a low-methionine diet, and o-rMETase was started as second-line treatment. Five months after beginning of the combination treatment, the patient had a subsequent FDG-PET scan and extensive eradication of almost all metastases was observed, with only a metastasis remaining in the liver.

Conclusion: o-rMETase in combination with immunotherapy and irradiation eradicated extensive metastases in a patient with breast cancer. Further investigation of this combination treatment for breast cancer is necessary including clinical trials.

Keywords: BAK; Breast cancer; FDG-PET; Hoffman effect; eradication; immunotherapy; metastasis; methionine addiction; oral recombinant methioninase; radiation.

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Conflict of interest statement

The Authors declare no competing interests regarding this work.

Figures

Figure 1
Figure 1
A female patient was diagnosed with left breast cancer with extensive metastases in her liver, lymph nodes, lungs, and bones using an [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) (A). After five months of treatment with a combination of radiation, immunotherapy with biological response modifier (BRM)-active killer (BAK), a low-methionine diet, and oral recombinant methioninase (o-rMETase), the extensive metastases were almost eradicated as seen with FDG-PET (B).
See this image and copyright information in PMC

References

    1. Hsu JY, Chang CJ, Cheng JS. Survival, treatment regimens and medical costs of women newly diagnosed with metastatic triple-negative breast cancer. Sci Rep. 2022;12(1):729. doi: 10.1038/s41598-021-04316-2. - DOI - PMC - PubMed
    1. Hoffman RM, Erbe RW. High in vivo rates of methionine biosynthesis in transformed human and malignant rat cells auxotrophic for methionine. Proc Natl Acad Sci USA. 1976;73(5):1523–1527. doi: 10.1073/pnas.73.5.1523. - DOI - PMC - PubMed
    1. Coalson DW, Mecham JO, Stern PH, Hoffman RM. Reduced availability of endogenously synthesized methionine for S-adenosylmethionine formation in methionine-dependent cancer cells. Proc Natl Acad Sci USA. 1982;79(14):4248–4251. doi: 10.1073/pnas.79.14.4248. - DOI - PMC - PubMed
    1. Stern PH, Mecham JO, Wallace CD, Hoffman RM. Reduced free‐methionine in methionine‐dependent SV40‐transformed human fibroblasts synthesizing apparently normal amounts of methionine. J Cell Physiol. 1983;117(1):9–14. doi: 10.1002/jcp.1041170103. - DOI - PubMed
    1. Kubota Y, Han Q, Masaki N, Hozumi C, Hamada K, Aoki Y, Obara K, Tsunoda T, Hoffman RM. Elimination of axillary-lymph-node metastases in a patient with invasive lobular breast cancer treated by first-line neo-adjuvant chemotherapy combined with methionine restriction. Anticancer Res. 2022;42(12):5819–5823. doi: 10.21873/anticanres.16089. - DOI - PubMed

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