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Publications

Journal Article Clinical Trial, Phase III Randomized Controlled Trial Ppublish 3 citations

PubMed: 38718683 DOI: 10.1016/j.ebiom.2024.105141

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.

EBioMedicine 104:105141

Authors: Sylvie Giacchetti, Enora Laas, Thomas Bachelot, Jérome Lemonnier, Fabrice André, David Cameron, Judith Bliss, Sylvie Chabaud, Anne-Claire Hardy-Bessard, Magali Lacroix-Triki, Jean-Luc Canon, Marc Debled, Mario Campone, Paul Cottu, Florence Dalenc, Annabelle Ballesta, Frederique Penault-Llorca, Bernard Asselain, Elise Dumas, Fabien Reyal, Paul Gougis, Francis Lévi, Anne-Sophie Hamy

Affiliations

  • AP-HP, Hôpital Saint Louis, Senologie, Paris and Chronotherapy, Cancers, and Transplantation Unit, Faculty of Medicine, Paris-Saclay University, France; Chronotherapy, Cancers and Transplatation Unit, Faculty of Medicine, Paris-Saclay, Villejuif, France.
  • Surgery Department, Institut Curie, Universite Paris Cite, Paris, France; RT2Lab, Residual Tumor and Response to Treatment, U932 "Immunity and Cancer", Universite Paris Cité, Paris, France.
  • Medical Oncology, Centre Leon Berard, Lyon, France.
  • R&D Unicancer, Paris, France.
  • Gustave Roussy, Villejuif, France.
  • ICR-CTSU, Division of Clinical Studies, The Institute of Cancer Research, London, United Kingdom.
  • Medical Oncology, Western General Hospital, Edinburgh, United Kingdom.
  • Department of Clinical Research and Innovation, Centre Leon Berard, Lyon, France.
  • Medical Oncology, CARIO, Plerin, France.
  • Medical Oncology, Grand Hopital de Charleroi, Charleroi, Belgium.
  • Medical Oncology, Institut Bergonie, Bordeaux, France.
  • Medical Oncology, Institut Cancerologie de l'Ouest, Saint Herblain, France.
  • Medical Oncology, Institut Curie, Universite Paris Cite, Paris, France.
  • Medical Oncology, Oncopole Claudius Regaud, IUCT, Toulouse, France.
  • U900, Institut Curie, Saint Cloud, France.
  • Centre Jean Perrin, Université Clermont Auvergne, INSERM, U1240 Imagerie Moléculaire et Stratégies Théranostiques, Clermont Ferrand, France.
  • Arcagy-Gineco, Paris, France.
  • RT2Lab, Residual Tumor and Response to Treatment, U932 "Immunity and Cancer", Universite Paris Cité, Paris, France; Department of Mathematics, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland; (t)"Chronotherapy, Cancers, and Transplantation" Unit, Faculty of Medicine, Paris-Saclay University, Villejuif, France.
  • RT2Lab, Residual Tumor and Response to Treatment, U932 "Immunity and Cancer", Universite Paris Cité, Paris, France.
  • Chronotherapy, Cancers and Transplatation Unit, Faculty of Medicine, Paris-Saclay, Villejuif, France.
  • Medical Oncology, Institut Curie, Universite Paris Cite, Paris, France; RT2Lab, Residual Tumor and Response to Treatment, U932 "Immunity and Cancer", Universite Paris Cité, Paris, France.

Abstract

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.

MeSH

Therapeutics, Breast Neoplasms, Biomedical Research, Disease-Free Survival, Tamoxifen, Artificial Intelligence

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