Differential involvement of autophagy and apoptosis in response to chemoendocrine and endocrine therapy in breast cancer: JBCRG-07TR

Takayuki Ueno, Norikazu Masuda, Shunji Kamigaki, Takashi Morimoto, Shigehira Saji, Shigeru Imoto, Hironobu Sasano, Masakazu Toi

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)


Endocrine therapy is an essential component in the curative treatment of hormone receptor (HR)-positive breast cancer. To improve treatment efficacy, the addition of metronomic chemotherapy has been tested and shown to improve therapeutic effects. To better understand cellular reactions to metronomic chemoendocrine therapy, we studied autophagy-related markers, beclin 1 and LC3, and apoptosis-related markers, TUNEL and M30, in pre-and post-treatment cancer tissues from a multicenter neoadjuvant trial, JBCRG-07, in which oral cyclophosphamide plus letrozole were administered to postmenopausal patients with HR-positive breast cancer. Changes in the levels of markers were compared with those following neoadjuvant endocrine therapy according to clinical response. Apoptosis, in addition to autophagy-related markers, increased following metronomic chemoendocrine therapy and such increases were associated with clinical response. By contrast, following endocrine therapy, the levels of apoptosis-related markers did not increase regardless of clinical response, whereas the levels of autophagy-related markers increased. Furthermore, levels of the apoptosis-related marker, M30, decreased in responders of endocrine therapy, suggesting that the induction of apoptosis by metronomic chemoendocrine therapy was involved in the improved clinical outcome compared with endocrine therapy. In conclusion, metronomic chemoendocrine therapy induced a different cellular reaction from that of endocrine therapy, including the induction of apoptosis, which is likely to contribute to improved efficacy compared with endocrine therapy alone.

Original languageEnglish
Article number984
JournalInternational journal of molecular sciences
Issue number4
Publication statusPublished - 2019 Feb 2


  • Apoptosis
  • Autophagy
  • Beclin 1
  • Chemoendocrine therapy
  • Endocrine therapy
  • LC3
  • M30
  • Metronomic

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


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