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Utility of human epidermal growth factor 2 heterogeneity as a prognostic factor in triple-negative breast cancer

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Abstract

In some cases of human epidermal growth factor 2 (HER2)-negative breast cancer, including triple-negative breast cancer, HER2 expression is sporadically and strongly upregulated, a condition known as HER2 heterogeneity. We investigated the clinicopathological features of patients with HER2 heterogeneity in triple-negative breast cancers treated with neoadjuvant chemotherapy. Thirty-nine patients with triple-negative breast cancer who had undergone preoperative chemotherapy participated in this study. To assess for HER2 heterogeneity, we used dual in situ hybridization slides. We evaluated the association between HER2 heterogeneity and clinicopathological factors such as rates of pathologic complete response (pCR) and of recurrence-free survival. Of the 39 patients, 15 (38.5%) had cancers with HER2 heterogeneity. The pCR rates were 13.3% among patients with HER2 heterogeneity and 20.8% among those with HER2 nonheterogeneity, but the difference was not significant. The recurrence-free survival rate was significantly lower in patients with HER2 heterogeneity than in those without (P = 0.025). HER2 heterogeneity is a significant predictor of poor prognosis in patients with triple-negative breast cancer treated with neoadjuvant chemotherapy.

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Data availability

The datasets generated or analyzed during this study are not publicly available because of regulation by the Institutional Review Board of the Gunma University, but they are available from the corresponding author on reasonable request.

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Acknowledgements

We gratefully acknowledge the work of our research technicians, Kumiko Sudo and Kei Masuda.

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Authors and Affiliations

  1. Department of Breast and Endocrine Surgery, National Hospital Organization Takasaki General Medical Center, Gunma, Japan

    Eriko Narusawa, Sasagu Kurozumi, Yukio Koibuchi, Daisuke Takata & Shoko Tokuda

  2. Department of General Surgical Science, Gunma University Graduate School of Medicine, Gunma, Japan

    Eriko Narusawa, Sasagu Kurozumi, Sayaka Obayashi, Ken Shirabe & Takaaki Fujii

  3. Department of Breast Surgery, International University of Health and Welfare, 852, Hatakeda, Narita City, Chiba, 286-8520, Japan

    Sasagu Kurozumi & Jun Horiguchi

  4. Department of Diagnostic Pathology, Gunma University Graduate School of Medicine, Gunma, Japan

    Ayaka Katayama & Tetsunari Oyama

  5. Department of Diagnostic Pathology, National Hospital Organization Takasaki General Medical Center, Gunma, Japan

    Akira Ogawa

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  1. Eriko Narusawa
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Contributions

EN, SK, AK, YK, and AO participated mainly in the study design, experimentation, analysis, interpretation, and manuscript drafting. EN, DT, and ST collected the clinical data and assisted in establishing the study design and evaluating the results obtained. SO, TO, JH, KS, and TF contributed to theoretical organization of the manuscript. All authors contributed to drafting and reviewing the manuscript and approved the submitted and final version.

Corresponding author

Correspondence to Sasagu Kurozumi.

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Conflict of interest

SK has received honoraria from Kyowa Kirin Co., Ltd.; Daiichi Sankyo Co. Ltd.; Taiho Pharmaceutical Co. Ltd.; Eli Lilly and Company, MSD K.K.; AstraZeneca K.K.; Chugai Pharmaceutical, Ltd.; Dinow Inc.; Eisai Co., Ltd.; Takeda Pharmaceutical Co., Ltd.; and Novartis Japan. TF received research funding from Eisai Co., Ltd. KS received research grants from Chugai Pharmaceutical Co., Ltd., and Ono Pharmaceutical Co., Ltd. The other authors declare that they have no conflicts of interest.

Ethical approval and consent to participate

This study was approved by National Hospital Organization Takasaki General Medical Center (reference no. 2020-46). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committees and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Narusawa, E., Kurozumi, S., Katayama, A. et al. Utility of human epidermal growth factor 2 heterogeneity as a prognostic factor in triple-negative breast cancer. Med Mol Morphol (2024). https://doi.org/10.1007/s00795-024-00386-z

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