Association between endocrine adjuvant therapy intake timing and disease-free survival in patients with high-risk early breast cancer: results of a sub-study of the UCBG- UNIRAD trial.
Date
2024-06-01ICR Author
Author
Giacchetti, S
Laas, E
Bachelot, T
Lemonnier, J
André, F
Cameron, D
Bliss, J
Chabaud, S
Hardy-Bessard, A-C
Lacroix-Triki, M
Canon, J-L
Debled, M
Campone, M
Cottu, P
Dalenc, F
Ballesta, A
Penault-Llorca, F
Asselain, B
Dumas, E
Reyal, F
Gougis, P
Lévi, F
Hamy, A-S
Type
Journal Article
Metadata
Show full item recordAbstract
BACKGROUND: Circadian rhythms regulate cellular physiology and could influence the efficacy of endocrine therapy (ET) in breast cancer (BC). We prospectively tested this hypothesis within the UNIRAD adjuvant phase III trial (NCT01805271). METHODS: 1278 patients with high-risk hormonal receptor positive (HR+)/HER2 negative (HER2-) primary BC were randomly assigned to adjuvant ET with placebo or everolimus. Patients prospectively reported in a diary the daily timing of ET intake among four 6-h slots (06:00-11:59 (morning), 12:00-17:59 (afternoon), 18:00-23:59 (evening), or 24:00-05:59 (nighttime). The association between ET timing and disease-free survival (DFS) was a prespecified secondary endpoint of the trial and the results of this observational study are reported here. FINDINGS: ET timing was recorded by 855 patients (67.2%). Patients declaring morning (n = 465, 54.4%) or afternoon (n = 45, 5.4%) ET intake were older than those declaring evening (n = 339, 39.6%) or nighttime (n = 5, 0.6%) intake. With a median follow-up of 46.7 months, 118 patients had a local (n = 30) or metastasis relapse (n = 84), and 41 patients died. ET intake timing was not associated with DFS in the whole population (HR = 0.77, 95% CI [0.53-1.12]). The association between ET intake timing and DFS according to the stratification factors revealed interactions with ET agent (tamoxifen versus Aromatase inhibitors (AI) with an increased DFS in the group of evening/nighttime versus morning/afternoon tamoxifen intake (HR = 0.43, 95% CI [0.22-0.85]), while no association was found for AI intake (HR = 1.07, 95% CI [0.68-1.69]). The interaction between ET intake timing and ET agent remained in multivariable analysis (HR = 0.38 [0.16-0.91]). INTERPRETATION: Tamoxifen intake in the evening/nighttime could be recommended in patients with high-risk HR+/HER2- BC while awaiting for results from further ET timing studies. FUNDING: UNIRAD was Supported by a grant from the French Ministry of Health PHRC 2012 and received funding from La Ligue contre le Cancer, Cancer Research-UK, Myriad Genetics, and Novartis.
Collections
Subject
Aromatase inhibitors
Breast cancer
Chronotherapy
Circadian rhythm
Endocrine therapy
Intake timing
Tamoxifen
Humans
Breast Neoplasms
Female
Middle Aged
Aged
Adult
Chemotherapy, Adjuvant
Antineoplastic Agents, Hormonal
Disease-Free Survival
Neoplasm Staging
Tamoxifen
Treatment Outcome
Circadian Rhythm
Antineoplastic Combined Chemotherapy Protocols
Research team
Clin Trials & Stats Unit
Language
eng
Date accepted
2024-04-16
License start date
2024-06-01
Citation
EBioMedicine, 2024, 104 pp. 105141 -
Publisher
ELSEVIER