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Prognostic significance of geminin expression levels in Ki67-high subset of estrogen receptor-positive and HER2-negative breast cancers

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Abstract

Background

Indication for chemotherapy in estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancers is determined on the basis of Ki67 expression level. However, since Ki67-high cancers are not necessarily sensitive to chemotherapy, identification of such patients who do not need chemotherapy is an important issue.

Patients and methods

We used immunohistochemical staining to examine the expression levels of ER, progesterone receptor (PgR), Ki67, and geminin, a marker of S to G2/M phases, in 80 ER-positive/HER2-negative breast cancers. The labeling indices of Ki67 and geminin were determined and cutoff values were set at 15 and 6 %, respectively.

Results

Ki67 and geminin expression levels were significantly associated with nuclear grade. In the Ki67-low subset, 26 out of 28 (92.9 %) cancers were geminin low and in the Ki67-high subset, 31 out of 52 (59.6 %) were geminin high. Distant disease-free survival (DDFS) of the geminin-high subset was significantly poorer than that of the geminin-low subset (P = 0.009). In the Ki67-low subset, only one patient showed recurrence. Metastasis was detected in eight out of 31 (25.8 %) patients in the geminin-high group of the Ki67-high subset, but no recurrence was observed in the geminin-low group of the Ki67-high subset.

Conclusion

Geminin-high breast cancers are significantly associated with worse prognosis. Since poorer prognosis was recognized only in the geminin-high group in Ki67-high cancers, we speculate that geminin may be useful for identifying patients in the Ki67-high subset who can avoid unnecessary chemotherapy.

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Conflict of interest

Y. Miyoshi has received honoraria from Chugai Pharmaceutical Co., Ltd., AstraZeneca K.K., GlaxoSmithKline K.K., and research funding from Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd. The other authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Surgery, Division of Breast and Endocrine, Hyogo College of Medicine, Mukogawa 1-1, Nishinomiya, Hyogo, 663-8501, Japan

    Tomoko Yagi, Natsuko Inoue, Ayako Yanai, Keiko Murase, Michiko Imamura, Yoshimasa Miyagawa, Yukie Enomoto, Arisa Nishimukai, Yuichi Takatsuka & Yasuo Miyoshi

  2. Surgical Pathology, Hyogo College of Medicine, Mukogawa 1-1, Nishinomiya, Hyogo, 663-8501, Japan

    Seiichi Hirota

  3. Department of Medical Informatics, Niigata University Medical and Dental Hospital, Asahimachidori 1-754, Chuo-ku, Niigata, 951-8520, Japan

    Kouhei Akazawa

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  1. Tomoko Yagi
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  2. Natsuko Inoue
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  3. Ayako Yanai
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  4. Keiko Murase
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  11. Kouhei Akazawa
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  12. Yasuo Miyoshi
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Correspondence to Yasuo Miyoshi.

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Yagi, T., Inoue, N., Yanai, A. et al. Prognostic significance of geminin expression levels in Ki67-high subset of estrogen receptor-positive and HER2-negative breast cancers. Breast Cancer 23, 224–230 (2016). https://doi.org/10.1007/s12282-014-0556-9

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  • DOI: https://doi.org/10.1007/s12282-014-0556-9

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