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. 2016 Mar;23(2):224-30.
doi: 10.1007/s12282-014-0556-9. Epub 2014 Aug 1.

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

Tomoko Yagi  1 , Natsuko Inoue  1 , Ayako Yanai  1 , Keiko Murase  1 , Michiko Imamura  1 , Yoshimasa Miyagawa  1 , Yukie Enomoto  1 , Arisa Nishimukai  1 , Yuichi Takatsuka  1 , Seiichi Hirota  2 , Kouhei Akazawa  3 , Yasuo Miyoshi  4
Affiliations

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

Tomoko Yagi et al. Breast Cancer. 2016 Mar.

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.

Keywords: Breast cancer; Geminin; Ki67; Luminal subtype; Prognosis.

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