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Menstrual cycle could affect Ki67 expression in estrogen receptor-positive breast cancer patients
  1. Yoshiya Horimoto1,2,
  2. Atsushi Arakawa3,
  3. Masahiko Tanabe1,
  4. Keiji Kuroda4,
  5. Joe Matsuoka5,
  6. Fumie Igari1,
  7. Takanori Himuro1,
  8. Yuko Yoshida1,
  9. Emi Tokuda1,
  10. Hideo Shimizu1,
  11. Okio Hino2,
  12. Mitsue Saito1
  1. 1Department of Breast Oncology, Juntendo University School of Medicine, Tokyo, Japan
  2. 2Department of Pathology and Oncology, Juntendo University School of Medicine, Tokyo, Japan
  3. 3Department of Human Pathology, Juntendo University School of Medicine, Tokyo, Japan
  4. 4Department of Obstetrics and Gynecology, Juntendo University School of Medicine, Tokyo, Japan
  5. 5Clinical Research Support Center, Juntendo University School of Medicine, Tokyo, Japan
  1. Correspondence to Dr Yoshiya Horimoto, Department of Breast Oncology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan; yoshiyahorimoto{at}hotmail.com

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.

  • BREAST CANCER
  • BREAST PATHOLOGY
  • SURGICAL PATHOLOGY

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