Late effects of adjuvant chemotherapy adumbrate dormancy complexity in breast cancer. Breast (Edinburgh, Scotland)

Romano Demicheli, Christine Desmedt, Mike Retsky, Christos Sotiriou, Martine Piccart, Elia Biganzoli

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: Dormant avascular micrometastases and single, or small groups of, non-proliferating cells are currently assumed to explain the multipeak dynamics of distant metastases (DM) following primary breast cancer surgical removal. METHODS: The hazard rate pattern for DM was analysed in 1518 premenopausal node-positive patients, enrolled in a series of randomized clinical trials on early breast cancer, which were carried out in Italy and Belgium. Patients underwent surgery alone (n = 397) or surgery plus adjuvant chemotherapy (n = 1121) and the minimal follow up was 15 years. RESULTS: The DM hazard rate for patients undergoing surgery alone displayed two early sharp peaks at 9 and 33 months, a wide intermediate one spanning from about 50 to 90 months and a late peak at 115-120 months. Adjuvant chemotherapy was associated with a prominent reduction of the two early peaks leaving a residual one at about 18 months and a reduction of the intermediate peak leaving two small peaks at about 50 and 80 months. The late peak remained unchanged. CONCLUSIONS: Present results reveal the ability of adjuvant chemotherapy to reduce not only the rate of early relapses, but also the rate of intermediate relapses at about the sixth year of follow up. Adjuvant chemotherapy is not impacting on the development of metastases underlying the late peak detected at the tenth year. These findings suggest the existence of a previously unknown dormancy state that, at the primary tumour surgical removal, results in evolving chemo-sensitive metastatic processes, and, moreover, of a later chemo-refractory dormancy state.
Original languageEnglish
Pages (from-to)64-70
Number of pages7
JournalBreast
Volume52
DOIs
Publication statusPublished - 2020

Keywords

  • Breast cancer
  • Adjuvant chemotherapy effects
  • Distant metastasis dynamics
  • Dormancy states
  • Surgery effects

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