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BRCAness of brain lesions reflects a worse outcome for patients with metastatic breast cancer

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Abstract

Purpose

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Breast cancer often metastasizes to the central nervous system. Although the prognosis of brain metastases from breast cancer has been considered poor, and systemic therapy has not contributed to an improved prognosis, newer agents are expected to be more effective. BRCAness is defined as the status of homologous recombination deficiency (HRD) in tumor tissue, regardless of the presence of pathogenic germline BRCA1/2 variants. A study employing next-generation sequencing analysis showed that HRD was found relatively frequently in brain metastases of breast cancer patients. However, there have been no studies evaluating BRCAness in brain metastases of breast cancer with more efficient, rapid, and cost-effective methods.

Methods

We retrospectively investigated 17 brain metastases of breast cancer that were surgically resected at our hospital from January 2007 to December 2022. Of these, samples from 15 patients were evaluable for BRCAness by employing multiplex ligation-dependent probe amplification (MLPA) assay.

Results

Of the 15 patients, five patients (33%) had tumors with BRCAness. Clinicopathological factors of patients with brain metastases with BRCAness were not statistically different from those of patients who possessed tumors without BRCAness. Patients with brain metastases with BRCAness had shorter overall survival compared to those without BRCAness (BRCAness, median 15 months (95% CI 2–30) vs. non-BRCAness, median 28.5 months (95% CI 10–60); P = 0.013).

Conclusion

In this study, we evaluated BRCAness in brain metastases of breast cancer with the MLPA method, and found that about one-third of patients had BRCAness-positive tumors. The analysis of BRCAness using MLPA has the potential for practical clinical use.

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Data Availability

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Acknowledgements

This study was supported by a Grant-in-Aid from the Japan Society for the Promotion of Science (JSPS) KAKENHI (Grant Number: 21K16388). The authors thank the Laboratory of Molecular and Biochemical Research, Biomedical Research Core Facilities, Juntendo University Graduate School of Medicine, for technical assistance. We also sincerely appreciate Clear Science Pty Ltd for language editing.

Funding

This study was supported by Japan Society for the Promotion of Science, 21K16388, Fumi Murakami.

Author information

Authors and Affiliations

  1. Department of Breast Oncology, Faculty of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan

    Yumiko Ishizuka, Yoshiya Horimoto, Fumi Murakami, Katsuya Nakai, Masami Arai & Junichiro Watanabe

  2. Department of Human Pathology, Faculty of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan

    Yoshiya Horimoto, Hiroko Onagi & Takuo Hayashi

  3. Department of Breast Surgery and Oncology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo, 160-8402, Japan

    Yoshiya Horimoto & Takashi Ishikawa

  4. Diagnostics and Therapeutics of Intractable Disease, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan

    Hidetaka Eguchi & Masami Arai

  5. Clinical Genetics, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan

    Masami Arai

Authors
  1. Yumiko Ishizuka
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Contributions

YI, YH, and KN designed this study. YI, YH, and KN collected clinical data. YH, HO and TH conducted pathological diagnosis. YI, YH, and HE conducted data analysis and statistics. YI and YH drafted the original manuscript. HE, FM, TI, MA, and JW substantively revised the manuscript. All authors have read and approved the final version of the manuscript.

Corresponding author

Correspondence to Yoshiya Horimoto.

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The authors have no relevant financial or non-financial interests to disclose.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the Ethics Committee of Juntendo University Hospital (H16-0096-H01) and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Ishizuka, Y., Horimoto, Y., Eguchi, H. et al. BRCAness of brain lesions reflects a worse outcome for patients with metastatic breast cancer. Breast Cancer Res Treat 203, 49–55 (2024). https://doi.org/10.1007/s10549-023-07115-7

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