Late effects of adjuvant chemotherapy adumbrate dormancy complexity in breast cancer.
Belgium
/ epidemiology
Breast Neoplasms
/ pathology
Chemotherapy, Adjuvant
Female
Humans
Italy
/ epidemiology
Lymphatic Metastasis
/ drug therapy
Neoplasm Micrometastasis
/ drug therapy
Premenopause
Proportional Hazards Models
Randomized Controlled Trials as Topic
Secondary Prevention
/ statistics & numerical data
Adjuvant chemotherapy effects
Breast cancer
Distant metastasis dynamics
Dormancy states
Surgery effects
Journal
Breast (Edinburgh, Scotland)
ISSN: 1532-3080
Titre abrégé: Breast
Pays: Netherlands
ID NLM: 9213011
Informations de publication
Date de publication:
Aug 2020
Aug 2020
Historique:
received:
18
10
2019
revised:
30
04
2020
accepted:
04
05
2020
pubmed:
20
5
2020
medline:
20
3
2021
entrez:
20
5
2020
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
BACKGROUND
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
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
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
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.
Identifiants
pubmed: 32428688
pii: S0960-9776(20)30109-0
doi: 10.1016/j.breast.2020.05.002
pmc: PMC7375586
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
64-70Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare that they have no competing interests.
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