Tomoko Yagi1, Natsuko Inoue1, Ayako Yanai1, Keiko Murase1, Michiko Imamura1, Yoshimasa Miyagawa1, Yukie Enomoto1, Arisa Nishimukai1, Yuichi Takatsuka1, Seiichi Hirota2, Kouhei Akazawa3, Yasuo Miyoshi4. 1. Department of Surgery, Division of Breast and Endocrine, Hyogo College of Medicine, Mukogawa 1-1, Nishinomiya, Hyogo, 663-8501, Japan. 2. Surgical Pathology, Hyogo College of Medicine, Mukogawa 1-1, Nishinomiya, Hyogo, 663-8501, Japan. 3. Department of Medical Informatics, Niigata University Medical and Dental Hospital, Asahimachidori 1-754, Chuo-ku, Niigata, 951-8520, Japan. 4. Department of Surgery, Division of Breast and Endocrine, Hyogo College of Medicine, Mukogawa 1-1, Nishinomiya, Hyogo, 663-8501, Japan. ymiyoshi@hyo-med.ac.jp.
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.
BACKGROUND: Indication for chemotherapy in estrogen receptor (ER)-positive and humanepidermal 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.
Entities:
Keywords:
Breast cancer; Geminin; Ki67; Luminal subtype; Prognosis
Authors: S Hernández-Pérez; E Cabrera; E Salido; M Lim; L Reid; S R Lakhani; K K Khanna; J M Saunus; R Freire Journal: Oncogene Date: 2017-03-13 Impact factor: 9.867