title: Menstrual cycle could affect Ki67 expression in estrogen receptor-positive breast cancer patients.
abstract: BACKGROUND
  Ki67 is a potent prognostic marker for determining systemic treatment of patients with hormone receptor-positive breast cancer. However, evaluation of Ki67 expression can be difficult, due mostly to its heterogeneity. The Ki67 expression level, which indicates that a cell is undergoing division (cell cycle), rises when proliferation activity increases. Thus, Ki67 expression might be affected by hormonal stimuli. We hypothesised that Ki67 expression level might change during the menstrual cycle. We examined pairs of biopsy and surgical specimens from individual patients to evaluate this hypothesis.
  
  
  METHODS
  First, the effects of estradiol on Ki67 expression in breast cancer cell lines were examined employing immunocytochemistry and Western blotting. Next, differences in Ki67 expression between biopsy and surgical specimens from 131 patients with estrogen receptor-positive tumours were retrospectively examined.
  
  
  RESULTS
  In vitro experiments showed Ki67 expression in estrogen receptor-positive cancer cells to be dependent on estradiol stimulation. Ki67 expression was higher in biopsy samples collected in the luteal phase than in those from other phases. When biopsy and surgical samples were obtained at different times during the menstrual cycle in the same individual, there were differences in Ki67 expression between these samples. Those collected in the luteal phase showed higher Ki67 expression than samples obtained during other phases (p<0.01).
  
  
  CONCLUSIONS
  Ki67 expression varied in the same patients according to menstrual cycle phase. Our results suggest that Ki67 expression in estrogen receptor-positive breast cancer should be carefully assessed bearing in mind the patient's menstrual cycle, since the interpretation of expression could affect treatment decisions.
authors.affiliation: Department of Breast Oncology, Juntendo University School of Medicine, Tokyo, Japan Department of Pathology and Oncology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Horimoto
authors.affiliation: Department of Human Pathology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Arakawa
authors.affiliation: Department of Breast Oncology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Tanabe
authors.affiliation: Department of Obstetrics and Gynecology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Kuroda
authors.affiliation: Clinical Research Support Center, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Joe
authors.initials: J
authors.lastname: Matsuoka
authors.affiliation: Department of Breast Oncology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Fumie
authors.initials: F
authors.lastname: Igari
authors.affiliation: Department of Breast Oncology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Himuro
authors.affiliation: Department of Breast Oncology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Yoshida
authors.affiliation: Department of Breast Oncology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Tokuda
authors.affiliation: Department of Breast Oncology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Shimizu
authors.affiliation: Department of Pathology and Oncology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Okio
authors.initials: O
authors.lastname: Hino
authors.affiliation: Department of Breast Oncology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Mitsue
authors.initials: M
authors.lastname: Saito
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D001706:Biopsy; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D049109:Cell Proliferation; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism*; D061986:MCF-7 Cells; D008597:Menstrual Cycle / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D004967:Estrogens; D019394:Ki-67 Antigen; D011960:Receptors, Estrogen; D004958:Estradiol
keywords: BREAST CANCER; BREAST PATHOLOGY; SURGICAL PATHOLOGY