Yoshiya Horimoto1, Atsushi Arakawa2, Masahiko Tanabe3, Keiji Kuroda4, Joe Matsuoka5, Fumie Igari3, Takanori Himuro3, Yuko Yoshida3, Emi Tokuda3, Hideo Shimizu3, Okio Hino6, Mitsue Saito3. 1. Department of Breast Oncology, Juntendo University School of Medicine, Tokyo, Japan Department of Pathology and Oncology, Juntendo University School of Medicine, Tokyo, Japan. 2. Department of Human Pathology, Juntendo University School of Medicine, Tokyo, Japan. 3. Department of Breast Oncology, Juntendo University School of Medicine, Tokyo, Japan. 4. Department of Obstetrics and Gynecology, Juntendo University School of Medicine, Tokyo, Japan. 5. Clinical Research Support Center, Juntendo University School of Medicine, Tokyo, Japan. 6. Department of Pathology and Oncology, Juntendo University School of Medicine, Tokyo, Japan.
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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Entities:
Keywords:
BREAST CANCER; BREAST PATHOLOGY; SURGICAL PATHOLOGY
Authors: Sarah M Bernhardt; Pallave Dasari; Danielle J Glynn; Lucy Woolford; Lachlan M Moldenhauer; David Walsh; Amanda R Townsend; Timothy J Price; Wendy V Ingman Journal: BMC Cancer Date: 2021-06-26 Impact factor: 4.430
Authors: Sarah M Bernhardt; Pallave Dasari; Joseph Wrin; Wendy Raymond; Suzanne Edwards; David Walsh; Amanda R Townsend; Timothy J Price; Wendy V Ingman Journal: Breast Cancer Res Date: 2020-08-18 Impact factor: 6.466