Progesterone receptor expression in proliferating cancer cells of hormone-receptor-positive breast cancer

Takayuki Ueno, Shigehira Saji, Tomohiro Chiba, Hiroshi Kamma, Hirotsugu Isaka, Hiroki Itoh, Kentaro Imi, Kaisuke Miyamoto, Manami Tada, Hironobu Sasano, Masakazu Toi, Shigeru Imoto

Research output: Contribution to journalArticle

Abstract

Breast cancer has been suggested to have two distinct driving mechanisms: the hormone receptor and the growth factor receptor pathways. We hypothesized that each driving system produces a different expression pattern of estrogen-regulated genes, such as progesterone receptor, in proliferating cells. Progesterone receptor and Ki67 expressions were assessed by dual-fluorescence immunohistochemistry in estrogen-receptor-positive breast cancer tissues. Two distinct proliferating cell populations were observed: progesterone-receptor-positive and progesterone-receptor-negative. In the training cohort, tissues with progesterone-receptor-positive proliferating cells were associated with lower grade and better disease-free survival (p = 0.0055 and 0.0026, respectively). These associations were confirmed in the validation cohort from the neoadjuvant endocrine trial JFMC34 (p = 0.033 and 0.0003, respectively). In the validation cohort, patients with progesterone-receptor-positive proliferating cells responded better to endocrine therapy and had a lower Oncotype DX Recurrence Score. In the multivariate analysis, progesterone receptor status of proliferating cells, but not progesterone receptor or Ki67 alone, was an independent predictor of disease-free survival in both cohorts (p = 0.0043 and 0.0026). In conclusion, the progesterone receptor status of proliferating cancer cells was associated with histological grade and Recurrence Score, and a potent prognostic factor in estrogen-receptor-positive breast cancers. Results suggest that different driving systems generate different expression patterns of progesterone receptor in proliferating cancer cells. Further studies are warranted to validate the findings.

Original languageEnglish
Pages (from-to)1010428318811025
JournalTumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine
Volume40
Issue number10
DOIs
Publication statusPublished - 2018 Nov 1

Keywords

  • Ki67
  • Progesterone receptor
  • Recurrence Score
  • luminal-type
  • prognosis

ASJC Scopus subject areas

  • Cancer Research

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